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A Study to Evaluate Efficacy and Safety of Daprodustat Compared to Darbepoetin Alfa in Japanese Hemodialysis (HD)-Dependent Subjects With Anemia Associated With Chronic Kidney Disease (CKD)

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ClinicalTrials.gov Identifier: NCT02969655
Recruitment Status : Completed
First Posted : November 21, 2016
Results First Posted : November 29, 2019
Last Update Posted : November 29, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Anaemia
Interventions Drug: Daprodustat small
Drug: Daprodustat small placebo
Drug: Daprodustat large
Drug: Daprodustat large placebo
Drug: Darbepoetin alfa
Drug: Darbepoetin alfa placebo
Enrollment 271
Recruitment Details A total of 50 centers, contracted in Japan, enrolled and randomized participants. A total of 271 participants were enrolled and randomized in this study.
Pre-assignment Details A total of 332 participants were screened of which 61 failed screening reasons being participants did not meet inclusion/exclusion criteria (48), physician decision (3) and withdrawn by participant (10), hence 271 participants were enrolled and randomized.
Arm/Group Title Daprodustat Darbepoetin Alfa
Hide Arm/Group Description Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks. Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Period Title: Overall Study
Started 136 135
Completed 115 120
Not Completed 21 15
Reason Not Completed
Withdrawal by Subject             3             2
Physician Decision             4             3
Protocol-specified withdrawal criteria             4             2
Adverse Event             10             8
Arm/Group Title Daprodustat Darbepoetin Alfa Total
Hide Arm/Group Description Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks. Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks. Total of all reporting groups
Overall Number of Baseline Participants 136 135 271
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 136 participants 135 participants 271 participants
64.1  (10.30) 63.5  (10.54) 63.8  (10.40)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 136 participants 135 participants 271 participants
Female
45
  33.1%
46
  34.1%
91
  33.6%
Male
91
  66.9%
89
  65.9%
180
  66.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Count of participants
Asian - Japanese heritage Number Analyzed 136 participants 135 participants 271 participants
136 135 271
1.Primary Outcome
Title Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)
Hide Description The mean hemoglobin during the Evaluation Period was estimated by a statistical model.
Time Frame Weeks 40 to 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) Population comprised of all randomized participants who had a Baseline and at least one post Baseline schedule Hgb assessment.
Arm/Group Title Daprodustat Darbepoetin Alfa
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 133 134
Least Squares Mean (Standard Error)
Unit of Measure: Grams per deciliter (g/dL)
10.89  (0.062) 10.83  (0.060)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Daprodustat, Darbepoetin Alfa
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was established if the lower limit of the 95% CI was greater than -1.0 g/dL. Even if the 95% CI for the difference was completely negative (i.e. lied fully within the range -1.0 to <0 g/dL) non-inferiority was concluded on condition that the mean Hgb estimated in the daprodustat group was within the target range.
Statistical Test of Hypothesis P-Value <.0001
Comments The p value on this table is one-sided and calculated for the non-inferiority assessment.
Method Mixed model repeated measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.11 to 0.23
Estimation Comments Analysis was performed by a MMRM with covariates of treatment, Baseline Hgb, visit, treatment-by-visit interaction, Baseline-by-visit interaction.
2.Secondary Outcome
Title Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)
Hide Description The percentage of participants with observed mean Hgb within the target range during the primary efficacy evaluation period was summarized. Odds ratio was estimated using a logistic regression and provided along with its 95% CI and a one-sided p-value.
Time Frame Weeks 40 to 52
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent to treat (mITT) comprised of all ITT participants who had at least one Hgb measurement during the evaluation period.
Arm/Group Title Daprodustat Darbepoetin Alfa
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 120 125
Measure Type: Number
Unit of Measure: Percentage of participants
Responder 88 90
Non-responder 13 10
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Daprodustat, Darbepoetin Alfa
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7442
Comments The p value on this table is one-sided and calculated for the superiority assessment.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.34 to 1.71
Estimation Comments Analysis was performed by logistic regression with covariates of treatment and Baseline Hgb.
3.Secondary Outcome
Title Change From Baseline in Hgb (Hgb Increase Rate) at Week 4
Hide Description Change from Baseline was calculated as the post-dose Week 4 visit value minus the Baseline value.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Daprodustat Darbepoetin Alfa
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 133 134
Mean (Standard Deviation)
Unit of Measure: g/dL
-0.42  (0.898) 0.08  (0.525)
4.Secondary Outcome
Title Percentage of Participants by Hgb Change From Baseline Category at Week 4
Hide Description Percentage of participants within each category were provided only for daprodustat and the categories were classified into 6 (i.e., <=-2, >-2 to -1, >-1 to 0, >0 to 1, >1 to 2, >2 grams per deciliter [g/dL]). In addition, 'within 1.0 g/dL (i.e., <=-1 and >=1) and over 2.0 g/dL (i.e., <-2 and >2) categories were provided.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Data for Darbepoetin alfa group could not be collected as comparison was not reasonable because of the difference in dose adjustment frequency.
Arm/Group Title Daprodustat
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Overall Number of Participants Analyzed 133
Measure Type: Number
Unit of Measure: Percentage of participants
<= -2.0 5
> -2.0 and <= -1.0 21
> -1.0 and <= 0 44
> 0 and <= 1.0 27
> 1.0 and <= 2.0 4
> 2.0 0
within +/- 1.0 75
over +/- 2.0 5
5.Secondary Outcome
Title Distribution of Daprodustat Dose Level by Visit
Hide Description Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Daprodustat. Median along with the interquartile range (25th and 75th percentile) has been presented.
Time Frame Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44, and 48)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title Daprodustat
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Overall Number of Participants Analyzed 133
Median (Inter-Quartile Range)
Unit of Measure: milligrams per day (mg/day)
Day 1, n=133 Number Analyzed 133 participants
4.0
(4.0 to 4.0)
Week 4, n=133 Number Analyzed 133 participants
4.0
(4.0 to 6.0)
Week 8, n=126 Number Analyzed 126 participants
4.0
(4.0 to 6.0)
Week 12, n=125 Number Analyzed 125 participants
6.0
(4.0 to 6.0)
Week 16, n=123 Number Analyzed 123 participants
6.0
(4.0 to 8.0)
Week 20, n=123 Number Analyzed 123 participants
6.0
(4.0 to 8.0)
Week 24, n=123 Number Analyzed 123 participants
6.0
(4.0 to 8.0)
Week 28, n=123 Number Analyzed 123 participants
6.0
(4.0 to 8.0)
Week 32, n=122 Number Analyzed 122 participants
6.0
(4.0 to 8.0)
Week 36, n=121 Number Analyzed 121 participants
6.0
(4.0 to 8.0)
Week 40, n=119 Number Analyzed 119 participants
6.0
(4.0 to 8.0)
Week 44, n=117 Number Analyzed 117 participants
6.0
(4.0 to 8.0)
Week 48, n=117 Number Analyzed 117 participants
6.0
(4.0 to 8.0)
6.Secondary Outcome
Title Distribution of Darbepoetin Alfa Dose Level by Visit
Hide Description Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Darbepoetin Alfa. Median along with the interquartile range (25th and 75th percentile) has been presented.
Time Frame Day 1, Weeks 2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48, and 50
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title Darbepoetin Alfa
Hide Arm/Group Description:
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 134
Median (Inter-Quartile Range)
Unit of Measure: micrograms per week (ug/week)
Day 1, n=134 Number Analyzed 134 participants
15.0
(15.0 to 30.0)
Week 2. n=134 Number Analyzed 134 participants
15.0
(15.0 to 30.0)
Week 4, n=134 Number Analyzed 134 participants
15.0
(10.0 to 30.0)
Week 6, n=133 Number Analyzed 133 participants
15.0
(10.0 to 30.0)
Week 8, n=131 Number Analyzed 131 participants
15.0
(10.0 to 30.0)
Week 10, n=129 Number Analyzed 129 participants
15.0
(10.0 to 30.0)
Week 12, n=129 Number Analyzed 129 participants
15.0
(10.0 to 30.0)
Week 14, n=129 Number Analyzed 129 participants
15.0
(10.0 to 30.0)
Week 16, n=129 Number Analyzed 129 participants
15.0
(10.0 to 30.0)
Week 18, n=129 Number Analyzed 129 participants
15.0
(10.0 to 30.0)
Week 20, n=129 Number Analyzed 129 participants
15.0
(10.0 to 30.0)
Week 22, n=128 Number Analyzed 128 participants
15.0
(10.0 to 30.0)
Week 24, n=129 Number Analyzed 129 participants
15.0
(10.0 to 30.0)
Week 26, n=129 Number Analyzed 129 participants
15.0
(10.0 to 30.0)
Week 28, n=127 Number Analyzed 127 participants
15.0
(10.0 to 30.0)
Week 30, n=128 Number Analyzed 128 participants
15.0
(10.0 to 30.0)
Week 32, n=127 Number Analyzed 127 participants
15.0
(10.0 to 30.0)
Week 34, n=127 Number Analyzed 127 participants
15.0
(10.0 to 30.0)
Week 36, n=127 Number Analyzed 127 participants
15.0
(10.0 to 30.0)
Week 38, n=127 Number Analyzed 127 participants
15.0
(10.0 to 30.0)
Week 40, n=125 Number Analyzed 125 participants
15.0
(10.0 to 30.0)
Week 42, n=125 Number Analyzed 125 participants
15.0
(10.0 to 30.0)
Week 44, n=125 Number Analyzed 125 participants
15.0
(10.0 to 30.0)
Week 46, n=125 Number Analyzed 125 participants
15.0
(10.0 to 30.0)
Week 48, n=124 Number Analyzed 124 participants
15.0
(10.0 to 30.0)
Week 50, n=122 Number Analyzed 122 participants
15.0
(10.0 to 30.0)
7.Secondary Outcome
Title Duration of Treatment Interruption Due to Hgb >13 g/dL
Hide Description Duration of treatment interruption due to Hgb >13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for the daprodustat group.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the time of assessment were used for analysis. Summary data for Darbepoetin alfa group could not be collected as comparison was not reasonable because of the difference in dose adjustment frequency. Median along with inter quartile range (25th and 75th percentile) have been presented.
Arm/Group Title Daprodustat
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Overall Number of Participants Analyzed 3
Median (Inter-Quartile Range)
Unit of Measure: Days
28.0
(28.0 to 56.0)
8.Secondary Outcome
Title Number of Dose Adjustments for Daprodustat
Hide Description Number of dose adjustments has been presented only for daprodustat.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Summary data for Darbepoetin alfa group could not be collected as comparison was not reasonable because of the difference in dose adjustment frequency.
Arm/Group Title Daprodustat
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Overall Number of Participants Analyzed 133
Median (Full Range)
Unit of Measure: Dose adjustments
2.0
(0 to 6)
9.Secondary Outcome
Title Hgb Values at Each Assessment Visit
Hide Description Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.
Time Frame Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title Daprodustat Darbepoetin Alfa
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 133 134
Mean (Standard Deviation)
Unit of Measure: g/dL
Baseline (Day 1), n=133, 134 Number Analyzed 133 participants 134 participants
10.94  (0.770) 10.82  (0.732)
Week 4, n=133, 134 Number Analyzed 133 participants 134 participants
10.52  (0.984) 10.90  (0.829)
Week 8, n=127, 132 Number Analyzed 127 participants 132 participants
10.50  (1.069) 11.01  (0.824)
Week 12, n=125, 129 Number Analyzed 125 participants 129 participants
10.53  (0.989) 11.09  (0.753)
Week 16, n=124, 129 Number Analyzed 124 participants 129 participants
10.57  (0.970) 10.92  (0.862)
Week 20, n=123, 129 Number Analyzed 123 participants 129 participants
10.85  (0.784) 10.95  (0.830)
Week 24, n=123, 129 Number Analyzed 123 participants 129 participants
11.01  (0.718) 10.92  (0.859)
Week 28, n=123, 129 Number Analyzed 123 participants 129 participants
10.97  (0.748) 10.86  (0.872)
Week 32, n=122, 127 Number Analyzed 122 participants 127 participants
11.10  (0.829) 10.96  (0.820)
Week 36, n=121, 127 Number Analyzed 121 participants 127 participants
11.12  (0.827) 10.91  (0.847)
Week 40, n=120, 125 Number Analyzed 120 participants 125 participants
10.97  (0.860) 10.90  (0.835)
Week 44, n=117, 125 Number Analyzed 117 participants 125 participants
10.98  (0.912) 10.87  (0.904)
Week 48, n=117, 124 Number Analyzed 117 participants 124 participants
10.94  (0.893) 10.76  (0.830)
Week 52,n=115, 120 Number Analyzed 115 participants 120 participants
10.79  (0.807) 10.79  (0.841)
10.Secondary Outcome
Title Change From Baseline in Hgb Values at Each Assessment Visit
Hide Description Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calcuated as the post-dose visit value minus the Baseline value. Change from Baseline Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.
Time Frame Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title Daprodustat Darbepoetin Alfa
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 133 134
Mean (Standard Deviation)
Unit of Measure: g/dL
Week 4, n=133, 134 Number Analyzed 133 participants 134 participants
-0.42  (0.898) 0.08  (0.525)
Week 8, n=127, 132 Number Analyzed 127 participants 132 participants
-0.45  (1.178) 0.20  (0.821)
Week 12, n=125, 129 Number Analyzed 125 participants 129 participants
-0.42  (1.258) 0.27  (1.021)
Week 16, n=124, 129 Number Analyzed 124 participants 129 participants
-0.38  (1.348) 0.09  (1.146)
Week 20, n=123, 129 Number Analyzed 123 participants 129 participants
-0.09  (1.161) 0.12  (1.120)
Week 24, n=123, 129 Number Analyzed 123 participants 129 participants
0.07  (1.106) 0.10  (1.068)
Week 28, n=123, 129 Number Analyzed 123 participants 129 participants
0.03  (1.084) 0.04  (1.080)
Week 32, n=122, 127 Number Analyzed 122 participants 127 participants
0.16  (1.119) 0.14  (1.071)
Week 36, n=121, 127 Number Analyzed 121 participants 127 participants
0.17  (1.020) 0.09  (1.041)
Week 40, n=120, 125 Number Analyzed 120 participants 125 participants
0.03  (1.060) 0.10  (1.034)
Week 44, n=117, 125 Number Analyzed 117 participants 125 participants
0.03  (1.118) 0.07  (1.019)
Week 48, n=117, 124 Number Analyzed 117 participants 124 participants
-0.01  (1.164) -0.04  (0.978)
Week 52,n=115, 120 Number Analyzed 115 participants 120 participants
-0.16  (1.169) 0.01  (1.019)
11.Secondary Outcome
Title Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit
Hide Description Percentage of participants with Hgb within the target range was summarized at each assessment visit by treatment group have been presented.
Time Frame Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title Daprodustat Darbepoetin Alfa
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 133 134
Measure Type: Number
Unit of Measure: Percentage of participants
Baseline (Day 1), n=133, 134 Number Analyzed 133 participants 134 participants
79 87
Week 4, n=133,134 Number Analyzed 133 participants 134 participants
65 80
Week 8, n=127,132 Number Analyzed 127 participants 132 participants
65 84
Week 12, n=125,129 Number Analyzed 125 participants 129 participants
66 86
Week 16, n=124,129 Number Analyzed 124 participants 129 participants
64 80
Week 20, n=123,129 Number Analyzed 123 participants 129 participants
82 81
Week 24, n=123,129 Number Analyzed 123 participants 129 participants
85 81
Week 28, n=123,129 Number Analyzed 123 participants 129 participants
85 82
Week 32, n=122, 127 Number Analyzed 122 participants 127 participants
79 80
Week 36, n=121,127 Number Analyzed 121 participants 127 participants
78 78
Week 40, n=120,125 Number Analyzed 120 participants 125 participants
77 80
Week 44, n=117,125 Number Analyzed 117 participants 125 participants
74 82
Week 48, n=117,124 Number Analyzed 117 participants 124 participants
77 79
Week 52, n=115,120 Number Analyzed 115 participants 120 participants
77 80
12.Secondary Outcome
Title Percentage of Time in Hgb Target Range (10.0 to 12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)
Hide Description Percentage of time in Hgb target range (10.0 to 12.0 g/dL) during the primary efficacy evaluation period (Weeks 40 to 52) for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.
Time Frame Weeks 40 to 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time point were analyzed.
Arm/Group Title Daprodustat Darbepoetin Alfa
Hide Arm/Group Description:
Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 118 125
Mean (Standard Deviation)
Unit of Measure: Percentage of time
76.81  (30.387) 80.23  (28.038)
13.Secondary Outcome
Title Number of Participants Who Had an Hgb Level of Less Than 7.5 g/dL
Hide Description If an initial Hgb value was less than 7.5 g/dL, measurement was repeated at the same study visit (using the same sample) to calculate the average. If the average met the Hgb stopping criteria, study treatment was permanently discontinued. Number of participants who had an Hgb level of less than 7.5 g/dL has been presented.
Time Frame Up to Week 52
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ITT Population
Arm/Group Title Daprodustat Darbepoetin Alfa
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Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 133 134
Measure Type: Number
Unit of Measure: Percentage of participants
0 0
14.Secondary Outcome
Title Number of Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks
Hide Description Number of participants who had an Hgb increase of more than 2 g/dL over any 4 weeks for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.
Time Frame Up to Week 52
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ITT Population
Arm/Group Title Daprodustat Darbepoetin Alfa
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Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 133 134
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.8%
2
   1.5%
15.Secondary Outcome
Title Number of Participants Who Had an Hgb Level of More Than 13.0 g/dL
Hide Description Number of participants who had an Hgb increase of more than 13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.
Time Frame Up to Week 52
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ITT Population
Arm/Group Title Daprodustat Darbepoetin Alfa
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Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 133 134
Measure Type: Number
Unit of Measure: Percentage of participants
7 8
16.Secondary Outcome
Title Number of Episodes With Hgb Level of More Than 13.0 g/dL
Hide Description Number of episodes with Hgb level of more than 13.0 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.
Time Frame Up to Week 52
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ITT Population
Arm/Group Title Daprodustat Darbepoetin Alfa
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Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
Overall Number of Participants Analyzed 133 134
Measure Type: Number
Unit of Measure: Episodes
9 12
17.Secondary Outcome
Title Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat
Hide Description Blood samples for Pharmacokinetic (PK) analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). NA indicates geometric co-efficient of variation could not be calculated as a single participant was analyzed. Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. PK population comprised of all daprodustat-treated participants from whom PK samples were collected and analyzed. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data.
Time Frame 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24
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PK Population
Arm/Group Title Daprodustat
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Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Overall Number of Participants Analyzed 125
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*nanograms per milliliter
1 mg, n=8 Number Analyzed 8 participants
27.57
(147.6%)
2 mg, n=24 Number Analyzed 24 participants
44.52
(139.2%)
4 mg, n=91 Number Analyzed 91 participants
72.68
(242.2%)
6 mg, n=61 Number Analyzed 61 participants
140.58
(238.9%)
8 mg, n=38 Number Analyzed 38 participants
170.41
(136.1%)
12 mg, n=17 Number Analyzed 17 participants
150.53
(176.4%)
18 mg, n=5 Number Analyzed 5 participants
488.93
(89.2%)
18.Secondary Outcome
Title Maximum Concentration (Cmax) of Plasma Daprodustat
Hide Description Blood samples for PK analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data.
Time Frame 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24
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PK Population
Arm/Group Title Daprodustat
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Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks.
Overall Number of Participants Analyzed 125
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanograms per milliliter
1 mg, n=8 Number Analyzed 8 participants
16.11
(105.7%)
2 mg, n=24 Number Analyzed 24 participants
25.16
(122.7%)
4 mg, n=91 Number Analyzed 91 participants
42.45
(237.9%)
6 mg, n=61 Number Analyzed 61 participants
83.60
(269.7%)
8 mg, n=38 Number Analyzed 38 participants
105.71
(110.9%)
12 mg, n=17 Number Analyzed 17 participants
108.58
(117.8%)
18 mg, n=5 Number Analyzed 5 participants
306.61
(61.0%)
Time Frame Adverse events and serious adverse events were collected from the start of study treatment until the follow-up contact (Day 1 up to Follow-up Visit [Week 54])
Adverse Event Reporting Description Safety population that comprised of all participants who received at least one dose of study treatment were used for the assessment of serious adverse events and non-serious adverse events.
 
Arm/Group Title Daprodustat Darbepoetin Alfa
Hide Arm/Group Description Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams [mg] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks. Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms [ug] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks.
All-Cause Mortality
Daprodustat Darbepoetin Alfa
Affected / at Risk (%) Affected / at Risk (%)
Total   0/136 (0.00%)      1/135 (0.74%)    
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Daprodustat Darbepoetin Alfa
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/136 (15.44%)      37/135 (27.41%)    
Cardiac disorders     
Cardiac failure congestive  1  0/136 (0.00%)  0 2/135 (1.48%)  2
Angina pectoris  1  1/136 (0.74%)  1 1/135 (0.74%)  1
Coronary artery stenosis  1  1/136 (0.74%)  1 1/135 (0.74%)  1
Arrhythmia  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Arteriosclerosis coronary artery  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Cardiac valve disease  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Palpitations  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Sinus node dysfunction  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Mitral valve incompetence  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Ventricular extrasystoles  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Gastrointestinal disorders     
Ileus  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Colitis ulcerative  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Intestinal perforation  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Lower gastrointestinal haemorrhage  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Nausea  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Duodenal perforation  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Large intestine polyp  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Upper gastrointestinal haemorrhage  1  1/136 (0.74%)  1 0/135 (0.00%)  0
General disorders     
Vessel puncture site haemorrhage  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Hepatobiliary disorders     
Bile duct stone  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Infections and infestations     
Pneumonia  1  1/136 (0.74%)  1 2/135 (1.48%)  3
Sepsis  1  0/136 (0.00%)  0 2/135 (1.48%)  2
Bacteraemia  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Diverticulitis  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Enteritis infectious  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Gangrene  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Herpes zoster  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Shunt infection  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Urinary tract infection  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Injury, poisoning and procedural complications     
Shunt stenosis  1  4/136 (2.94%)  4 6/135 (4.44%)  6
Shunt occlusion  1  1/136 (0.74%)  1 3/135 (2.22%)  3
Shunt malfunction  1  0/136 (0.00%)  0 2/135 (1.48%)  2
Arteriovenous fistula aneurysm  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Contusion  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Femur fracture  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Rib fracture  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Spinal compression fracture  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Forearm fracture  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Humerus fracture  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Pelvic fracture  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Procedural hypertension  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Investigations     
Blood pressure increased  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Metabolism and nutrition disorders     
Hypoglycaemia  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon adenoma  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Pancreatic carcinoma  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Salivary gland neoplasm  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Nervous system disorders     
Spondylitic myelopathy  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Renal and urinary disorders     
Hydronephrosis  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Reproductive system and breast disorders     
Endometrial hyperplasia  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary oedema  1  0/136 (0.00%)  0 1/135 (0.74%)  2
Skin and subcutaneous tissue disorders     
Pemphigoid  1  1/136 (0.74%)  1 0/135 (0.00%)  0
Vascular disorders     
Aortic stenosis  1  1/136 (0.74%)  1 1/135 (0.74%)  1
Hypertensive emergency  1  0/136 (0.00%)  0 1/135 (0.74%)  1
Peripheral arterial occlusive disease  1  0/136 (0.00%)  0 1/135 (0.74%)  1
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Daprodustat Darbepoetin Alfa
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   102/136 (75.00%)      102/135 (75.56%)    
Gastrointestinal disorders     
Diarrhoea  1  20/136 (14.71%)  24 12/135 (8.89%)  15
Vomiting  1  15/136 (11.03%)  20 11/135 (8.15%)  13
Nausea  1  9/136 (6.62%)  10 11/135 (8.15%)  13
Constipation  1  8/136 (5.88%)  10 6/135 (4.44%)  6
Abdominal discomfort  1  3/136 (2.21%)  3 7/135 (5.19%)  7
General disorders     
Pyrexia  1  7/136 (5.15%)  8 3/135 (2.22%)  4
Infections and infestations     
Nasopharyngitis  1  57/136 (41.91%)  110 73/135 (54.07%)  135
Pharyngitis  1  10/136 (7.35%)  11 6/135 (4.44%)  6
Gastroenteritis  1  7/136 (5.15%)  7 2/135 (1.48%)  2
Injury, poisoning and procedural complications     
Shunt stenosis  1  16/136 (11.76%)  30 15/135 (11.11%)  28
Contusion  1  17/136 (12.50%)  21 10/135 (7.41%)  12
Skin abrasion  1  10/136 (7.35%)  14 7/135 (5.19%)  7
Procedural hypotension  1  11/136 (8.09%)  16 5/135 (3.70%)  6
Musculoskeletal and connective tissue disorders     
Back pain  1  6/136 (4.41%)  6 10/135 (7.41%)  10
Arthralgia  1  5/136 (3.68%)  5 10/135 (7.41%)  13
Muscle spasms  1  7/136 (5.15%)  9 4/135 (2.96%)  5
Pain in extremity  1  1/136 (0.74%)  1 9/135 (6.67%)  10
Nervous system disorders     
Headache  1  8/136 (5.88%)  8 6/135 (4.44%)  8
Vascular disorders     
Hypertension  1  5/136 (3.68%)  9 8/135 (5.93%)  8
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02969655    
Other Study ID Numbers: 201754
First Submitted: November 17, 2016
First Posted: November 21, 2016
Results First Submitted: June 21, 2019
Results First Posted: November 29, 2019
Last Update Posted: November 29, 2019