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Roxadustat in the Treatment of Anemia in End Stage Renal Disease (ESRD) Patients on Stable Dialysis (Pyrenees)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02278341
Recruitment Status : Completed
First Posted : October 30, 2014
Results First Posted : August 26, 2020
Last Update Posted : August 26, 2020
Sponsor:
Collaborator:
FibroGen
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Anemia
End Stage Renal Disease (ESRD)
Interventions Drug: Roxadustat
Drug: Epoetin alfa
Drug: Darbepoetin alfa
Drug: Iron
Enrollment 838
Recruitment Details Study population consisted of participants with end-stage renal disease (ESRD) who were on stable hemodialysis (HD) or peritoneal dialysis (PD), and were also on stable treatment with epoetin (i.e. epoetin alfa, beta, theta, zeta, delta or omega) or darbepoetin alfa for anemia.
Pre-assignment Details Participants were randomized in a 1:1 ratio to roxadustat or ESA (epoetin alfa or darbepoetin alfa). Randomization was stratified by 5 factors: previous ESA treatment, region, history of cardiovascular, cerebrovascular or thromboembolic diseases, average weekly ESA dose 4 weeks prior to randomization and the screening hemaglobin (Hb) value.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Period Title: Overall Study
Started 415 421
Received Treatment 414 420
Completed 297 329
Not Completed 118 92
Reason Not Completed
Randomized but never received study drug             1             1
Adverse Event             3             0
Death             68             56
Withdrawal by Subject             30             19
Lost to Follow-up             0             1
Physician Decision             1             1
Miscellaneous             15             14
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent) Total
Hide Arm/Group Description Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. Total of all reporting groups
Overall Number of Baseline Participants 415 421 836
Hide Baseline Analysis Population Description
The analysis population was the All Randomized, which consisted of participants who were randomized into the study and had the available data.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 415 participants 421 participants 836 participants
61  (13.8) 61.8  (13.4) 61.4  (13.6)
[1]
Measure Analysis Population Description: The analysis population was the All Randomized population.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 415 participants 421 participants 836 participants
Female
169
  40.7%
185
  43.9%
354
  42.3%
Male
246
  59.3%
236
  56.1%
482
  57.7%
[1]
Measure Analysis Population Description: The analysis population was the All Randomized population.
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 415 participants 421 participants 836 participants
WHITE
405
  97.6%
408
  96.9%
813
  97.2%
BLACK OR AFRICAN AMERICAN
6
   1.4%
6
   1.4%
12
   1.4%
ASIAN
2
   0.5%
3
   0.7%
5
   0.6%
OTHER
2
   0.5%
4
   1.0%
6
   0.7%
[1]
Measure Analysis Population Description: The analysis population was the All Randomized population.
Baseline Hemoglobin (Hb) Value   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 415 participants 421 participants 836 participants
<=11.0 g/dL
267
  64.3%
266
  63.2%
533
  63.8%
>11.0 g/dL
148
  35.7%
155
  36.8%
303
  36.2%
[1]
Measure Analysis Population Description: The analysis population was the All Randomized population.
Baseline Mean Hb   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  g/dL
Number Analyzed 415 participants 421 participants 836 participants
10.75  (0.62) 10.77  (0.62) 10.76  (0.62)
[1]
Measure Description: Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose).
[2]
Measure Analysis Population Description: The analysis population was the All Randomized population.
1.Primary Outcome
Title Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)]
Hide Description Baseline Hb was defined as the mean of four central laboratory Hb values; four latest Hb values prior or on the same date as the first study drug intake. For participants who did not have an available Hb value during the week 28-36 period, imputation rules were applied. For analyses without rescue therapy, participants who used rescue therapy after the initiation of rescue therapy were set to missing for 6 weeks from the start date of rescue therapy. If no Hb value was available, an imputation technique was used, with the mean of all available values from Day 1 to minimum (End of Efficacy Emergent Period) carried forward.
Time Frame Baseline and weeks 28 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the Per Protocol Set (PPS) which consisted of all Full Analysis Set (FAS) participants who did not meet any of exclusion criteria from the PPS. The FAS consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose valid Hb assessment.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 354 381
Least Squares Mean (95% Confidence Interval)
Unit of Measure: g/dL
0.428
(0.350 to 0.506)
0.193
(0.117 to 0.268)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb and baseline Hb by visit as continuous variable.
Type of Statistical Test Non-Inferiority
Comments Non Inferiority, Margin = -0.75
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for non-inferiority test based on 1-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.235
Confidence Interval (2-Sided) 95%
0.132 to 0.339
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)]
Hide Description Baseline Hb was defined as the mean of four central laboratory Hb values: four latest Hb values prior or on the same date as first study drug intake. Change from baseline to the average Hb are observed values. Missing hemoglobin data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model with treatment, baseline hemoglobin, randomization stratification factors and the available non missing hemoglobin for each scheduled week.
Time Frame Baseline and weeks 28 to 52
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the All Randomized, which consisted of participants who received at least one dose of study drug, and who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Least Squares Mean (95% Confidence Interval)
Unit of Measure: g/dL
0.363
(0.288 to 0.438)
0.192
(0.121 to 0.262)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable. Statistical analysis used was ANCOVA model with multiple imputations (MI). Missing hemoglobin data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the MCMC imputation model.
Type of Statistical Test Non-Inferiority
Comments Non-Inferiority, Margin = -0.75
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for non-inferiority test based on 1-sided significance level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.171
Confidence Interval (2-Sided) 95%
0.082 to 0.261
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Hb Response During Weeks 28 to 36
Hide Description Hb response during weeks 28-36, was defined as mean Hb from 10-12 g/dL without receiving rescue therapy in the 6 weeks prior to, or during, the evaluation period. The percentages and 95% CI were unadjusted, the exact method of Clopper-Pearson was used for 95% CI. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to end of treatment (EOT) Visit or last non-missing Hb assessment (for participants who died during the treatment period).
Time Frame Weeks 28 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PPS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 386 397
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
84.2
(80.2 to 87.7)
82.4
(78.3 to 86.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments A generalized linear model was used to estimate the difference in response rates between the arms, as an approximation for the Miettinen and Nurminen method, adjusting for following covariates: region, previous ESA treatment, cardiovascular history and baseline Hb as categorical variables.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority of roxadustat versus ESA (the non-inferiority margin for the difference between groups is -15%).
Statistical Test of Hypothesis P-Value <0.05
Comments p-value for non-inferiority test based on 1-sided significance level.
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Percentages
Estimated Value 2.3
Confidence Interval (2-Sided) 95%
-2.9 to 7.6
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28
Hide Description Baseline LDL was defined as the LDL value on Day 1. If this value was missing, the latest value prior to first study drug administration was used.
Time Frame Baseline and weeks 12 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS, with participants who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 394 412
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/L
-0.459
(-0.517 to -0.401)
-0.082
(-0.138 to -0.026)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline LDL, baseline Hb as continuous variables.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -0.377
Confidence Interval (2-Sided) 95%
-0.451 to -0.304
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Monthly Intravenous (IV) Iron Use
Hide Description Participants with no or missing medication records of IV Iron have their monthly IV Iron use set to 0 mg. For participants who took IV Iron, but without a dosing frequency, the average values were set to missing.
Time Frame Day 1 to week 36
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS, with participants who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 419
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg per month
21.6
(14.0 to 29.3)
53.5
(46.0 to 61.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -31.9
Confidence Interval (2-Sided) 95%
-41.4 to -22.4
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From BL in Short Form-36 (SF-36) Health Survey Physical Functioning (PF) Sub-score to the Average of Weeks 12 to 28
Hide Description Baseline SF-36 PF was defined as the SF-36 PF value on Day 1.The SF-36 is a Quality of Life (QoL) instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 contains 36 items that measure eight scales: (1) physical functioning (PF); (2) role limitations due to physical health problems (RP); (3) bodily pain (BP); (4) social functioning (SF); (5) general health perceptions (GH); (6) role limitations due to emotional problems (RE); (7) vitality, energy or fatigue (VT); and (8) mental health(MH). Each scale is transformed into 0-100 score, with higher scores indicating better health status. The SF-36 PF consists of 11 questions focused on health and ability to do usual activities, with higher scores indicating better health status.
Time Frame Baseline and weeks 12 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PPS, with participants who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 376 391
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
0.050
(-0.640 to 0.740)
-0.155
(-0.825 to 0.514)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment arm, region, CV History, previous ESA treatment, visits (week 8, week 12, week 28) and visit by treatment as categorical variables, and baseline SF-36 PF, baseline Hb as continuous variables.
Type of Statistical Test Non-Inferiority
Comments The margin for non-inferiority was -3.
Statistical Test of Hypothesis P-Value <0.05
Comments p-value for non-inferiority test based on 1-sided significance level
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.205
Confidence Interval (2-Sided) 95%
-0.649 to 1.059
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From BL in SF-36 Vitality (VT) Sub-score to the Average of Weeks 12 to 28
Hide Description Baseline VT Subscore was defined as the VT value on Day 1. The SF-36 is a QoL instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 vitality has four questions with score range from 0-100 with higher scores indicating better vitality status.
Time Frame Baseline and weeks 12 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PPS, with participants who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 377 391
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
0.460
(-0.329 to 1.249)
-0.396
(-1.165 to 0.373)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment arm, region, CV History, previous ESA treatment, visits (week 8, week 12, week 28) and visit by treatment as categorical variables, and baseline SF-36 VT, baseline Hb as continuous variables.
Type of Statistical Test Non-Inferiority
Comments The margin for non-inferiority was -3.
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.856
Confidence Interval (2-Sided) 95%
-0.115 to 1.828
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From BL in Mean Arterial Pressure (MAP) to the Average of Weeks 20 to 28
Hide Description Baseline MAP was defined as the MAP value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)*DBP + (1/3)*SBP.
Time Frame Baseline and weeks 20 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PPS, with participants who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 373 388
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmHg
-0.969
(-1.838 to -0.099)
-0.120
(-0.972 to 0.732)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables, and baseline MAP, baseline Hb as continuous variables.
Type of Statistical Test Non-Inferiority
Comments The margin for non-inferiority was 1.
Statistical Test of Hypothesis P-Value <0.05
Comments p-value for non-inferiority test based on 1-sided significance level
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -0.849
Confidence Interval (2-Sided) 95%
-1.971 to 0.273
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time to First Occurrence of an Increase in Blood Pressure
Hide Description Increase in Blood Pressure was defined as either: Systolic Blood Pressure (SBP) ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: Diastolic Blood Pressure (DBP) ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. For participants who have experienced more than one event, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time Frame Weeks 1 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PPS, with participants who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. .
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 386 397
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 12
11.7
(8.5 to 14.9)
11.1
(8.0 to 14.2)
Week 24
15.9
(12.2 to 19.6)
15.4
(11.9 to 19.0)
Week 36
21.1
(14.0 to 28.2)
23.5
(16. to 30.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment, and adjusting on Hb at baseline as continuous covariate. Non-inferiority was declared if the upper bound of the 95% CI is below 1.3.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority (hazard ratio margin of 1.3).
Statistical Test of Hypothesis P-Value <0.05
Comments p-value for non-inferiority test based on 1-sided significance level.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.924
Confidence Interval (2-Sided) 95%
0.669 to 1.276
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of Weeks 20 to 28
Hide Description Baseline MAP was defined as the MAP value on day 1. If this value was missing, the latest value prior to first study drug administration was used. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)*DBP + (1/3)*SBP.
Time Frame Baseline and weeks 20 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS, with participants who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 381 401
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmHg
-0.739
(-1.600 to 0.123)
-0.160
(-0.997 to 0.678)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables, and baseline MAP, baseline Hb as continuous variables.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.308
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -0.579
Confidence Interval (2-Sided) 95%
-1.694 to 0.536
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Time to First Occurrence of an Increase in Blood Pressure
Hide Description Increase in Blood Pressure was defined as either: SBP ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: DBP ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time Frame Weeks 1 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS, with participants who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 12
11.6
(8.5 to 14.8)
12.0
(8.9 to 15.1)
Week 24
16.1
(12.5 to 19.7)
16.2
(12.6 to 19.7)
Week 36
21.2
(14.1 to 28.3)
24.1
(16.7 to 31.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment, and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI is lower than 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.582
Comments p-value for superiority test based on 2-sided significance level.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.915
Confidence Interval (2-Sided) 95%
0.668 to 1.254
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy
Hide Description Hb response was defined as mean Hb during weeks 28 to 36 within the target range of 10.0 to 12.0 g/dL. The percentages and 95% CI are unadjusted, the exact method of Clopper-Pearson was used for 95% CI.
Time Frame Weeks 28 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
83.1
(79.1 to 86.5)
82.1
(78.1 to 85.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments A generalized linear model was used to estimate the difference in response rates between the arms, as an approximation for the Miettinen and Nurminen method, adjusting for following covariates: region, previous ESA treatment, cardiovascular history and baseline Hb as categorical variables.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.609
Comments p-value for superiority test based on 2-sided significance level
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Percentages
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-3.8 to 6.5
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From BL in Hb to Each Postdosing Time Point
Hide Description Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose).
Time Frame Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18,20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72,76, 80, 84, 88, 92, 96, 100, and 104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Least Squares Mean (95% Confidence Interval)
Unit of Measure: g/dL
Hb Change From BL to Week 1 Number Analyzed 407 participants 411 participants
0.232
(0.164 to 0.300)
0.068
(0.000 to 0.135)
Hb Change From BL to Week 2 Number Analyzed 401 participants 411 participants
0.496
(0.420 to 0.572)
0.054
(-0.022 to 0.129)
Hb Change From BL to Week 3 Number Analyzed 394 participants 408 participants
0.633
(0.552 to 0.714)
0.071
(-0.008 to 0.151)
Hb Change From BL to Week 4 Number Analyzed 399 participants 413 participants
0.803
(0.715 to 0.891)
0.095
(0.009 to 0.181)
Hb Change From BL to Week 5 Number Analyzed 399 participants 407 participants
0.723
(0.633 to 0.812)
-0.045
(-0.133 to 0.043)
Hb Change From BL to Week 6 Number Analyzed 391 participants 405 participants
0.868
(0.776 to 0.959)
0.138
(0.048 to 0.228)
Hb Change From BL to Week 7 Number Analyzed 389 participants 404 participants
0.698
(0.606 to 0.791)
-0.031
(-0.122 to 0.060)
Hb Change From BL to Week 8 Number Analyzed 393 participants 402 participants
0.816
(0.724 to 0.907)
0.116
(0.026 to 0.206)
Hb Change From BL to Week 10 Number Analyzed 396 participants 409 participants
0.640
(0.546 to 0.735)
-0.019
(-0.111 to 0.073)
Hb Change From BL to Week 12 Number Analyzed 384 participants 399 participants
0.732
(0.634 to 0.830)
0.139
(0.043 to 0.235)
Hb Change From BL to Week 14 Number Analyzed 383 participants 400 participants
0.508
(0.408 to 0.608)
0.005
(-0.093 to 0.103)
Hb Change From BL to Week 16 Number Analyzed 381 participants 401 participants
0.613
(0.511 to 0.716)
0.244
(0.144 to 0.344)
Hb Change From BL to Week 18 Number Analyzed 378 participants 395 participants
0.380
(0.283 to 0.477)
0.017
(-0.078 to 0.112)
Hb Change From BL to Week 20 Number Analyzed 376 participants 394 participants
0.501
(0.405 to 0.596)
0.217
(0.124 to 0.309)
Hb Change From BL to Week 22 Number Analyzed 370 participants 395 participants
0.266
(0.170 to 0.363)
0.069
(-0.025 to 0.163)
Hb Change From BL to Week 24 Number Analyzed 362 participants 388 participants
0.262
(0.168 to 0.356)
0.075
(-0.017 to 0.166)
Hb Change From BL to Week 26 Number Analyzed 359 participants 387 participants
0.316
(0.220 to 0.412)
0.073
(-0.020 to 0.165)
Hb Change From BL to Week 28 Number Analyzed 360 participants 388 participants
0.549
(0.452 to 0.647)
0.342
(0.248 to 0.437)
Hb Change From BL to Week 30 Number Analyzed 352 participants 380 participants
0.333
(0.236 to 0.429)
0.106
(0.013 to 0.198)
Hb Change From BL to Week 32 Number Analyzed 346 participants 376 participants
0.310
(0.211 to 0.409)
0.111
(0.016 to 0.207)
Hb Change From BL to Week 34 Number Analyzed 342 participants 374 participants
0.364
(0.268 to 0.460)
0.084
(-0.007 to 0.176)
Hb Change From BL to Week 36 Number Analyzed 339 participants 373 participants
0.482
(0.382 to 0.581)
0.225
(0.130 to 0.320)
Hb Change From BL to Week 40 Number Analyzed 336 participants 373 participants
0.199
(0.095 to 0.304)
0.064
(-0.036 to 0.163)
Hb Change From BL to Week 44 Number Analyzed 328 participants 367 participants
0.335
(0.221 to 0.448)
0.252
(0.145 to 0.360)
Hb Change From BL to Week 48 Number Analyzed 323 participants 365 participants
0.158
(0.047 to 0.270)
0.131
(0.027 to 0.236)
Hb Change From BL to Week 52 Number Analyzed 308 participants 363 participants
0.385
(0.273 to 0.496)
0.186
(0.082 to 0.290)
Hb Change From BL to Week 56 Number Analyzed 311 participants 360 participants
0.217
(0.104 to 0.329)
0.069
(-0.035 to 0.174)
Hb Change From BL to Week 60 Number Analyzed 299 participants 353 participants
0.368
(0.256 to 0.479)
0.171
(0.067 to 0.275)
Hb Change From BL to Week 64 Number Analyzed 289 participants 344 participants
0.181
(0.067 to 0.295)
-0.093
(-0.198 to 0.012)
Hb Change From BL to Week 68 Number Analyzed 290 participants 349 participants
0.306
(0.195 to 0.416)
0.100
(-0.002 to 0.202)
Hb Change From BL to Week 72 Number Analyzed 284 participants 339 participants
0.109
(-0.005 to 0.222)
-0.009
(-0.113 to 0.095)
Hb Change From BL to Week 76 Number Analyzed 278 participants 338 participants
0.401
(0.280 to 0.521)
0.189
(0.079 to 0.299)
Hb Change From BL to Week 80 Number Analyzed 274 participants 327 participants
0.087
(-0.028 to 0.203)
-0.015
(-0.120 to 0.091)
Hb Change From BL to Week 84 Number Analyzed 270 participants 328 participants
0.318
(0.199 to 0.438)
0.126
(0.017 to 0.235)
Hb Change From BL to Week 88 Number Analyzed 258 participants 326 participants
0.026
(-0.091 to 0.144)
-0.018
(-0.124 to 0.088)
Hb Change From BL to Week 92 Number Analyzed 255 participants 313 participants
0.357
(0.232 to 0.483)
0.154
(0.041 to 0.267)
Hb Change From BL to Week 96 Number Analyzed 253 participants 312 participants
0.126
(0.010 to 0.242)
-0.058
(-0.163 to 0.046)
Hb Change From BL to Week 100 Number Analyzed 248 participants 311 participants
0.302
(0.175 to 0.430)
0.138
(0.024 to 0.253)
Hb Change From BL to Week 104 Number Analyzed 240 participants 299 participants
0.232
(0.100 to 0.363)
0.133
(0.014 to 0.251)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 1- The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.164
Confidence Interval (2-Sided) 95%
0.072 to 0.256
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 2- The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.443
Confidence Interval (2-Sided) 95%
0.339 to 0.546
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 3 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.561
Confidence Interval (2-Sided) 95%
0.451 to 0.672
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 4 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.708
Confidence Interval 95%
0.588 to 0.828
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 5 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.768
Confidence Interval (2-Sided) 95%
0.645 to 0.890
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 6 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.729
Confidence Interval (2-Sided) 95%
0.604 to 0.855
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 7 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.729
Confidence Interval (2-Sided) 95%
0.603 to 0.856
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 8 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.700
Confidence Interval (2-Sided) 95%
0.574 to 0.826
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 10 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.659
Confidence Interval (2-Sided) 95%
0.530 to 0.788
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 12 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.593
Confidence Interval (2-Sided) 95%
0.459 to 0.727
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 14 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.503
Confidence Interval (2-Sided) 95%
0.366 to 0.640
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 16 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.369
Confidence Interval (2-Sided) 95%
0.229 to 0.510
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 18 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.363
Confidence Interval (2-Sided) 95%
0.230 to 0.496
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 20 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.284
Confidence Interval (2-Sided) 95%
0.154 to 0.414
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 22 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.003
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.197
Confidence Interval (2-Sided) 95%
0.065 to 0.329
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 24 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.004
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.187
Confidence Interval (2-Sided) 95%
0.059 to 0.316
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 26 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.243
Confidence Interval (2-Sided) 95%
0.113 to 0.373
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 28 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.002
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.207
Confidence Interval (2-Sided) 95%
0.074 to 0.340
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 30 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.227
Confidence Interval (2-Sided) 95%
0.096 to 0.358
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 32 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.004
Comments [Not Specified]
Method Mixed Models Analysis
Comments p-value for superiority test based on 2-sided significance level.
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.199
Confidence Interval (2-Sided) 95%
0.064 to 0.334
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 34 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.279
Confidence Interval 95%
0.150 to 0.409
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 36- The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.256
Confidence Interval (2-Sided) 95%
0.121 to 0.391
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 40 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.060
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.136
Confidence Interval (2-Sided) 95%
-0.006 to 0.277
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 44 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.293
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.082
Confidence Interval (2-Sided) 95%
-0.071 to 0.236
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 48 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.723
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.027
Confidence Interval (2-Sided) 95%
-0.123 to 0.177
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 52 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.009
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.199
Confidence Interval (2-Sided) 95%
0.049 to 0.348
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 56 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.056
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.147
Confidence Interval (2-Sided) 95%
-0.004 to 0.298
Estimation Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 60 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.010
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.196
Confidence Interval (2-Sided) 95%
0.047 to 0.346
Estimation Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 64 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.275
Confidence Interval (2-Sided) 95%
0.123 to 0.427
Estimation Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 68 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.006
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.206
Confidence Interval (2-Sided) 95%
0.059 to 0.353
Estimation Comments [Not Specified]
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 72 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.127
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.118
Confidence Interval (2-Sided) 95%
-0.033 to 0.269
Estimation Comments [Not Specified]
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 76 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.010
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.211
Confidence Interval (2-Sided) 95%
0.051 to 0.371
Estimation Comments [Not Specified]
Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 80 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.191
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.102
Confidence Interval (2-Sided) 95%
-0.051 to 0.255
Estimation Comments [Not Specified]
Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 84 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.018
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.192
Confidence Interval (2-Sided) 95%
0.033 to 0.351
Estimation Comments [Not Specified]
Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 88 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.576
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.044
Confidence Interval (2-Sided) 95%
-0.111 to 0.200
Estimation Comments [Not Specified]
Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 92 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.017
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.203
Confidence Interval (2-Sided) 95%
0.037 to 0.369
Estimation Comments [Not Specified]
Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 96 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.019
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.184
Confidence Interval (2-Sided) 95%
0.031 to 0.338
Estimation Comments [Not Specified]
Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 100 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.056
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.164
Confidence Interval 95%
-0.004 to 0.333
Estimation Comments [Not Specified]
Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Week 104 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.267
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.099
Confidence Interval (2-Sided) 95%
-0.076 to 0.273
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy
Hide Description Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). Averaged Hb values over weeks 28-36, weeks 44-52 and weeks 96-104 are observed values.
Time Frame Weeks 28 to 36, 44 to 52, and 96 to 104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Least Squares Mean (95% Confidence Interval)
Unit of Measure: g/dL
Average Hb Over Weeks 28-36 Number Analyzed 362 participants 393 participants
11.183
(11.100 to 11.265)
10.946
(10.867 to 11.025)
Average Hb Over Weeks 44-52 Number Analyzed 330 participants 370 participants
11.099
(11.009 to 11.189)
10.994
(10.909 to 11.079)
Average Hb Over Weeks 96-104 Number Analyzed 252 participants 317 participants
11.007
(10.904 to 11.110)
10.858
(10.766 to 10.950)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Weeks 28-36 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value for superiority test based on 2-sided significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.237
Confidence Interval (2-Sided) 95%
0.127 to 0.347
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Weeks 44-52 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.086
Comments p-value for superiority test based on 2-sided significance level
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.105
Confidence Interval (2-Sided) 95%
-0.015 to 0.225
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Weeks 96-104 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.031
Comments p-value for superiority test based on 2-sided significance level
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.149
Confidence Interval (2-Sided) 95%
0.014 to 0.284
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy
Hide Description Change from baseline to the average Hb are observed values. Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose).
Time Frame Baseline and weeks 28 to 36, 44 to 52, and 96 to 104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Least Squares Mean (95% Confidence Interval)
Unit of Measure: g/dL
Hb Change From BL to Weeks 28-36 Number Analyzed 364 participants 393 participants
0.408
(0.325 to 0.491)
0.173
(0.093 to 0.252)
Hb Change From BL to Weeks 44-52 Number Analyzed 331 participants 371 participants
0.298
(0.203 to 0.394)
0.194
(0.104 to 0.284)
Hb Change From BL to Weeks 96-104 Number Analyzed 254 participants 318 participants
0.225
(0.119 to 0.331)
0.076
(-0.020 to 0.171)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Weeks 28-36 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.235
Confidence Interval (2-Sided) 95%
0.125 to 0.346
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Weeks 44-52 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.110
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.104
Confidence Interval (2-Sided) 95%
-0.024 to 0.232
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Weeks 96-104 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.036
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.149
Confidence Interval (2-Sided) 95%
0.010 to 0.288
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy
Hide Description Percentage for each participant was calculated as Number of Hb values >= 10.0 g/dL / Total number of Hb values*100 in weeks 28 to 36, 44 to 52 and 96 to 104 without use of rescue therapy within 6 weeks prior to and during the 8 week evaluation period.
Time Frame Weeks 28-36, 44-52 and 96-104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: percentage of Hb values
Weeks 28-36 Number Analyzed 364 participants 393 participants
93.002  (18.320) 87.286  (25.114)
Weeks 44-52 Number Analyzed 331 participants 371 participants
89.421  (24.267) 86.914  (25.366)
Weeks 96-104 Number Analyzed 254 participants 318 participants
88.858  (24.708) 83.543  (30.296)
17.Secondary Outcome
Title Percentage of Hb Values Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy
Hide Description Percentage for each participant was calculated as Number of Hb values within 10.0-12.0 g/dL / Total number of Hb values*100 in weeks 28 to 36, 44 to 52 and 96 to 104 without use of rescue therapy within 6 weeks prior to and during the 8 week evaluation period.
Time Frame Weeks 28-36, 44-52 and 96-104
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Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: percentage of Hb values
Weeks 28-36 Number Analyzed 364 participants 393 participants
76.326  (28.175) 76.098  (28.991)
Weeks 44-52 Number Analyzed 331 participants 371 participants
75.891  (31.047) 74.634  (30.589)
Weeks 96-104 Number Analyzed 254 participants 318 participants
76.522  (30.378) 73.690  (33.040)
18.Secondary Outcome
Title Number of Hospitalizations
Hide Description The number of hospitalizations per participant were calculated during the Efficacy Emergent Period. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). It included all Non-Hemodialysis (HD) hospitalizations. The HD days were not counted as hospitalizations, even when performed overnight.
Time Frame Baseline to End of Treatment (EOT) (Up to week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS, with participants who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: Hospitalizations
0.9  (1.3) 0.9  (1.5)
19.Secondary Outcome
Title Number of Days of Hospitalization Per Year
Hide Description The number of days of hospitalizations per year was calculated as the sum of the durations of all non-HD hospitalizations in days (Date of discharge - Date of admission + 1)] / (duration of efficacy emergent period in days / 365.25). In case of missing dates, the hospitalization duration was imputed by the average duration per stay derived from the participants with non-missing duration within the same treatment group.
Time Frame Baseline to EOT (Up to week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS, with participants who had available data.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: Days per year
12.186  (34.121) 7.868  (22.948)
20.Secondary Outcome
Title Time to First Hospitalization
Hide Description Time to first hospitalization in years was defined in years as: (First event date during the Efficacy Emergent Period - Analysis date of First dose intake +1)/365.25, and the 'First event date' was defined as 'Date of first Admission and 'Analysis Date of first dose intake. For participants without hospitalization, the time to censoring was calculated as: (Date of End of Efficacy Emergent Period - Analysis Date of first dose intake + 1) / 365.25. Date of End of Efficacy Emergent Period was defined as as the treatment period up to the EOT visit. For participants who have experienced more than one hospitalization, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time Frame Baseline to EOT (Up to week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Year 0.5
19.4
(15.5 to 23.3)
18.3
(14.6 to 22.0)
Year 1
32.0
(27.3 to 36.6)
32.7
(28.2 to 37.3)
Year 1.5
43.5
(38.5 to 48.6)
41.9
(37.0 to 46.7)
Year 2
52.6
(47.5 to 57.8)
48.3
(43.3 to 53.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.164
Comments p-value for superiority test based on 2-sided significance level
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.154
Confidence Interval (2-Sided) 95%
0.943 to 1.411
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Time to First Use of Rescue Therapy
Hide Description Rescue therapy was defined as red blood cell (RBC) transfusion for both treatment groups and ESA for roxadustat participants. Only rescue medication that was started during the study treatment and up to end of efficacy emergent period was taken into account and considered as use of rescue medication. For participants who have experienced more than one use of rescue therapy, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time Frame Baseline to EOT (Up to week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Year 0.5
3.9
(2.0 to 5.8)
3.2
(1.5 to 4.8)
Year 1
8.2
(5.4 to 11.1)
8.4
(5.6 to 11.1)
Year 1.5
11.4
(8.1 to 14.8)
10.9
(7.8 to 14.0)
Year 2
12.8
(9.3 to 16.4)
14.4
(10.8 to 18.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.917
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.979
Confidence Interval (2-Sided) 95%
0.656 to 1.462
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Time to First RBC Transfusion
Hide Description For participants who have experienced more than one RBC transfusion, only their first event following study treatment was used. For RBC transfusions, when the number of units was not given but the volume transfused was, the number of units were estimated by volume transfused/250 mL (for transfusion of packed cell units) or volume transfused/500 mL (for transfusion of full blood). Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time Frame Baseline to EOT (Up to week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Year 0.5
3.6
(1.8 to 5.5)
3.2
(1.5 to 4.8)
Year 1
7.4
(4.7 to 10.1)
8.4
(5.6 to 11.1)
Year 1.5
10.0
(6.9 to 13.2)
10.9
(7.8 to 14.0)
Year 2
11.4
(8.0 to 14.9)
14.4
(10.8 to 18.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment, and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.501
Comments p-value for superiority test based on 2-sided significance level
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.867
Confidence Interval (2-Sided) 95%
0.573 to 1.313
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Mean Monthly Number of RBC Packs Per Participant
Hide Description During efficacy emergent period, the mean monthly number of RBC packs was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. Participants without medication records of RBC have their number of RBC packs and volume set to 0.
Time Frame Baseline to EOT (Up to week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Least Squares Mean (95% Confidence Interval)
Unit of Measure: RBC packs per month
0.026
(0.01 to 0.04)
0.032
(0.02 to 0.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model included treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.507
Comments p-value for superiority test based on 2-sided significance level
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -0.006
Confidence Interval (2-Sided) 95%
-0.02 to 0.01
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Mean Monthly Volume of RBC Transfusion Per Participant
Hide Description During Efficacy Emergent Period, the mean monthly volume of blood transfused was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).
Time Frame Baseline to EOT (Up to week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mL per month
6.061
(2.82 to 9.30)
5.929
(2.74 to 9.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model included treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.949
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.132
Confidence Interval (2-Sided) 95%
-3.90 to 4.16
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Time to First Use of IV Iron Supplementation
Hide Description For participants who have received more than one IV iron, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time Frame Baseline to EOT (Up to week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Year 0.5
11.2
(8.1 to 14.3)
33.5
(29.0 to 38.1)
Year 1
17.4
(13.5 to 21.2)
44.1
(39.3 to 49.0)
Year 1.5
23.6
(19.1 to 28.1)
55.0
(50.1 to 59.9)
Year 2
33.3
(26.0 to 40.7)
59.3
(54.4 to 64.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.368
Confidence Interval (2-Sided) 95%
0.291 to 0.465
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104
Hide Description Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg.
Time Frame Weeks 37-52 and weeks 53-104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg per month
Weeks 37-52
34.9
(20.9 to 48.9)
70.0
(56.9 to 83.2)
Weeks 53-104
49.5
(31.0 to 67.9)
98.1
(81.1 to 115.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Weeks 37-52 - Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg. The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -35.1
Confidence Interval (2-Sided) 95%
-51.8 to -18.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments Weeks 53-104 - Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg. The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -48.7
Confidence Interval (2-Sided) 95%
-70.3 to -27.0
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Percentage of Participants With Oral Iron Use Only
Hide Description Percentage of participants with/without IV iron only was calculated based on total number of participants within the Efficacy Emergent Period. The Efficacy Emergent Period is defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).
Time Frame Baseline to EOT (Up to week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Measure Type: Number
Unit of Measure: Percentage of participants
31.0 11.7
28.Secondary Outcome
Title Change From BL to Each Post-dosing Study Visit in Total Cholesterol
Hide Description Baseline assessment was the assessment from Day 1 visit. If baseline value was missing, then the latest screening period value was used as the baseline regardless of fasting status.
Time Frame Baseline and weeks 8, 28, 52, 104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: mmol/L
Change from BL to Week 8 Number Analyzed 392 participants 411 participants
-0.608  (0.889) -0.105  (0.712)
Change from BL to Week 28 Number Analyzed 364 participants 393 participants
-0.641  (0.960) -0.135  (0.805)
Change from BL to Week 52 Number Analyzed 318 participants 362 participants
-0.803  (1.027) -0.241  (0.906)
Change from BL to Week 104 Number Analyzed 247 participants 307 participants
-0.904  (1.053) -0.277  (1.002)
29.Secondary Outcome
Title Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio
Hide Description Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time Frame Baseline and weeks 8, 28, 52, 104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: Ratio
Change from BL to Week 8 Number Analyzed 390 participants 411 participants
-0.245  (0.818) -0.060  (0.726)
Change from BL to Week 28 Number Analyzed 362 participants 393 participants
-0.155  (1.046) -0.057  (0.922)
Change from BL to Week 52 Number Analyzed 317 participants 361 participants
-0.345  (0.904) -0.078  (0.886)
Change from BL to Week 104 Number Analyzed 246 participants 307 participants
-0.261  (1.167) -0.013  (1.048)
30.Secondary Outcome
Title Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol
Hide Description Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time Frame Baseline and weeks 8, 28, 52, 104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: mmol/L
Change from BL to Week 8 Number Analyzed 388 participants 404 participants
-0.518  (0.823) -0.107  (0.701)
Change from BL to Week 28 Number Analyzed 360 participants 391 participants
-0.540  (0.907) -0.127  (0.789)
Change from BL to Week 52 Number Analyzed 314 participants 360 participants
-0.700  (0.965) -0.229  (0.886)
Change from BL to Week 104 Number Analyzed 245 participants 304 participants
-0.788  (1.024) -0.240  (1.010)
31.Secondary Outcome
Title Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1)
Hide Description Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time Frame Baseline and weeks 8, 28, 52, 104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: g/L
Change from BL to Week 8 Number Analyzed 394 participants 415 participants
-0.114  (0.197) -0.006  (0.172)
Change from BL to Week 28 Number Analyzed 367 participants 393 participants
-0.113  (0.217) -0.012  (0.193)
Change from BL to Week 52 Number Analyzed 320 participants 366 participants
-0.097  (0.230) -0.013  (0.195)
Change from BL to Week 104 Number Analyzed 246 participants 309 participants
-0.097  (0.220) -0.012  (0.196)
32.Secondary Outcome
Title Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB)
Hide Description Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time Frame Baseline and weeks 8, 28, 52, 104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: mg/dL
Change from BL to Week 8 Number Analyzed 394 participants 415 participants
-11.03  (18.49) 1.00  (14.34)
Change from BL to Week 28 Number Analyzed 366 participants 393 participants
-11.18  (20.39) -0.12  (16.91)
Change from BL to Week 52 Number Analyzed 320 participants 366 participants
-13.18  (20.67) -0.01  (18.88)
Change from BL to Week 104 Number Analyzed 246 participants 309 participants
-13.50  (24.94) -0.01  (20.00)
33.Secondary Outcome
Title Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio
Hide Description Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used.
Time Frame Baseline and weeks 8, 28, 52, 104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: Ratio
Change from BL to Week 8 Number Analyzed 393 participants 415 participants
-0.037  (0.147) 0.013  (0.141)
Change from BL to Week 28 Number Analyzed 365 participants 392 participants
-0.034  (0.177) 0.002  (0.148)
Change from BL to Week 52 Number Analyzed 318 participants 365 participants
-0.051  (0.191) 0.007  (0.164)
Change from BL to Week 104 Number Analyzed 246 participants 309 participants
-0.062  (0.210) 0.007  (0.201)
34.Secondary Outcome
Title Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28
Hide Description Missing category for Fasting Only includes non-fasting participants and the participants with missing values.
Time Frame Weeks 12 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Measure Type: Number
Unit of Measure: Number of participants
Yes [Regardless of Fasting Status] 275 231
No [Regardless of Fasting Status] 119 181
Missing [Regardless of Fasting Status] 19 8
Yes [Fasting Only] 111 85
No [Fasting Only] 61 80
Missing [Fasting Only] 241 255
35.Secondary Outcome
Title Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal
Hide Description Achieved antihypertensive treatment goal was defined as SBP < 140 mmHg and DBP < 90 mmHg over an evaluation period based on the average of available values in weeks 12-28 (pre-dialysis).
Time Frame Weeks 12 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Measure Type: Number
Unit of Measure: Number of participants
Antihypertensive Treatment Achievement - Yes 264 261
Antihypertensive Treatment Achievement - No 130 149
Antihypertensive Treatment Achievement-Missing 19 10
36.Secondary Outcome
Title Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score (PCS)
Hide Description Baseline SF-36 PCS was defined as the SF-36 PCS value on Day 1. SF-36 contains 36-item that measures 8 scales with scores ranging from 0-100: physical functioning (PF); role limitations due to physical health problems (RP); bodily pain (BP); social functioning (SF); general health perceptions (GH); role limitations due to emotional problems (RE); vitality, energy or fatigue (VT); and mental health (MH). These scores are normed to the US population (norm-based scoring had very little impact on results when data was collected in Western European countries) to have a mean of 50 and standard deviation of 10. The PCS was calculated based on all 8 scales and ranges from 5.02-79.78. For each of these above scales, higher scores always indicating better health status.
Time Frame Baseline and weeks 12 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 384 404
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
0.560
(-0.029 to 1.148)
0.039
(-0.528 to 0.605)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline SF-36 PCS, baseline Hb, as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.161
Comments p-value for superiority test based on 2-sided significance level
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.521
Confidence Interval (2-Sided) 95%
-0.208 to 1.250
Estimation Comments [Not Specified]
37.Secondary Outcome
Title Change From BL to the Average of Weeks 12 to 28 in Anemia Subscale (AnS) ("Additional Concerns") of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score
Hide Description Baseline FACT-An AnS was defined as the FACT-An AnS value on Day 1. Together with the Functional Assessment of Cancer Therapy - General (FACT-G), the Anemia Subscale (AnS) is referred to as the FACT-An Total. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. The Anemia AnS score range is 0 to 80. For the above score, a higher score indicates better QoL.
Time Frame Baseline and weeks 12 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 384 403
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
0.534
(-0.486 to 1.554)
0.363
(-0.617 to 1.342)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline FACT-An Ans, baseline Hb, as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.788
Comments p-value for superiority test based on 2-sided significance level
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value 0.172
Confidence Interval (2-Sided) 95%
-1.083 to 1.426
Estimation Comments [Not Specified]
38.Secondary Outcome
Title Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score
Hide Description Baseline FACT-An Total Score was defined on Day 1. Total Fact-An score is composed of FACT-G and Ans scales. FACT-G contains 27 items that cover four dimensions of well-being: physical (PWB) - 7 items, functional (FWB) - 7 items, social/family (SWB) - 7 items, and emotional (EWB) - 6 items. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. The total score is obtained by summation of the scores from PWB, SWB, EWB, FWB and AnS. The FACT-An Total Score scale range is 0-188. A higher score indicates better QoL.
Time Frame Baseline and weeks 12 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 383 403
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
-0.392
(-2.466 to 1.681)
-0.287
(-2.276 to 1.701)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Roxadustat, ESA (Erythropoiesis-Stimulating Agent)
Comments The model includes treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline FACT-An Ans, baseline Hb, as continuous covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.936
Comments p-value for superiority test based on 2-sided significance level
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM Difference
Estimated Value -0.105
Confidence Interval (2-Sided) 95%
-2.672 to 2.462
Estimation Comments [Not Specified]
39.Secondary Outcome
Title Change From BL to the Average of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score
Hide Description Baseline assessment was defined as the value on Day 1. The EuroQol Questionnaire -5 Dimensions -5 Levels (EQ-5D-5L) is a self-reported questionnaire, used as a measure of respondents' Health Related Quality of Life (HRQoL) and utility values. The EQ-5D consists of the descriptive system and the visual analogue scale (VAS). The EQ-5D descriptive system comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems. The VAS records the respondent's self rated health status on a graduated (0-100) scale, where the endpoints are labeled 'Best imaginable health state' and 'Worst imaginable health state' with higher scores for higher HRQoL.
Time Frame Baseline and weeks 12 to 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 385 401
Mean (Standard Deviation)
Unit of Measure: Units on a scale
3.041  (14.910) 2.735  (14.477)
40.Secondary Outcome
Title Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC)
Hide Description The PGIC is a patient-rated instrument that measures change in participant's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), when compared to the start of treatment. The percentage of participants presented includes very much improved, much improved and minimally improved.
Time Frame Baseline and weeks 8, 12, 28, 36, 52, 76, 104
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Measure Type: Number
Unit of Measure: Percentage of participants
Week 8 59.6 49.5
Week 12 65.5 49.5
Week 28 62.3 57.1
Week 36 60.4 56.3
Week 52 57.1 55.3
Week 76 61.2 51.9
Week 104 61.6 51.3
41.Secondary Outcome
Title Change From BL in Serum Hepcidin
Hide Description Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time Frame Baseline and weeks 4, 12, 20, 36, 52, 104, and End of Study (EOS - up to 108 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS, with participants who had available data at baseline.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: µg/L
Week 4 Number Analyzed 387 participants 400 participants
-14.265  (42.393) -4.265  (33.518)
Week 12 Number Analyzed 375 participants 391 participants
-12.298  (41.335) -6.741  (38.507)
Week 20 Number Analyzed 361 participants 382 participants
-15.149  (43.152) -11.818  (41.596)
Week 36 Number Analyzed 332 participants 366 participants
-23.405  (43.033) -14.530  (43.449)
Week 52 Number Analyzed 310 participants 357 participants
-32.709  (42.342) -17.522  (47.307)
Week 104 Number Analyzed 242 participants 298 participants
-40.101  (48.611) -18.735  (51.632)
EOS Number Analyzed 280 participants 320 participants
-27.192  (52.169) -17.664  (51.688)
42.Secondary Outcome
Title Change From BL in Serum Ferritin
Hide Description Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time Frame Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, and EOS (up to 108 weeks)
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Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Roxadustat ESA (Erythropoiesis-Stimulating Agent)
Hide Arm/Group Description:
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa.
Overall Number of Participants Analyzed 413 420
Mean (Standard Deviation)
Unit of Measure: pmol/L
Week 4 Number Analyzed 400 participants 408 participants
-214.64  (824.96) -141.78  (456.15)
Week 8 Number Analyzed 394 participants 405 participants
-245.37  (668.51) -160.75  (607.39)
Week 12 Number Analyzed 389 participants 404 participants
-269.76  (761.24) -179.47  (586.95)
Week 20 Number Analyzed 379 participants 396 participants
-337.94  (645.73) -246.89  (727.64)
Week 28 Number Analyzed 363 participants