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A Study of Mycophenolate Mofetil (CellCept) in Management of Patients With Lupus Nephritis.

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: NCT00377637
Recruitment Status : Completed
First Posted : September 18, 2006
Results First Posted : December 6, 2011
Last Update Posted : December 6, 2011
Sponsor:
Collaborator:
Aspreva Pharmaceuticals
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lupus Nephritis
Interventions Drug: Mycophenolate mofetil (MMF)
Drug: Cyclophosphamide
Drug: Azathioprine
Drug: Placebo to Azathioprine
Drug: Placebo to Mycophenolate mofetil
Drug: Corticosteroid
Enrollment 370
Recruitment Details The induction phase was a prospective, randomized, open-label, active controlled, parallel group, international multicenter, 2-arm comparison study of MMF versus IVC in inducing a response in patients with Lupus nephritis. Responders in the induction phase were re-randomized into a double-blind, double-dummy, active controlled Maintenance Phase.
Pre-assignment Details  
Arm/Group Title Induction Phase: Cyclophosphamide Induction Phase: Mycophenolate Mofetil Maintenance Phase: Mycophenolate Mofetil Maintenance Phase: Azathioprine
Hide Arm/Group Description Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase. Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase. Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase. Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Period Title: Induction Phase
Started 185 [1] 185 [1] 0 0
Safety Population 180 184 0 0
Completed 156 150 0 0
Not Completed 29 35 0 0
Reason Not Completed
Adverse Event             12             21             0             0
Deterioration/serum creatinine             2             0             0             0
Dose reduction of MMF < 2 g/day for 14 d             0             1             0             0
Lost to Follow-up             2             1             0             0
Death             1             3             0             0
Withdrawal by Subject             5             6             0             0
Physician Decision             3             1             0             0
Sponsor decision             1             2             0             0
Non-Compliance             1             0             0             0
Reason for withdrawal is not noted             2             0             0             0
[1]
Intent-To-Treat
Period Title: Maintenance Phase
Started 0 0 116 111
Completed 0 0 73 54
Not Completed 0 0 43 57
Reason Not Completed
Adverse Event             0             0             29             43
Physician Decision             0             0             5             4
Lost to Follow-up             0             0             3             1
Withdrawal by Subject             0             0             3             3
Sponsor decision             0             0             2             3
Non-compliance             0             0             1             1
Study medication stopped > 14 days             0             0             0             1
Death             0             0             0             1
Arm/Group Title Induction Phase: Cyclophosphamide Induction Phase: Mycophenolate Mofetil Maintenance Phase: Mycophenolate Mofetil Maintenance Phase: Azathioprine Total
Hide Arm/Group Description Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase. Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase. Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase. Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase. Total of all reporting groups
Overall Number of Baseline Participants 185 185 116 111 597
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 185 participants 185 participants 116 participants 111 participants 597 participants
Induction Phase 31.3  (10.25) 32.4  (11.7) NA [1]   (NA) NA [1]   (NA) 31.9  (10.72)
Maintenance Phase NA [2]   (NA) NA [2]   (NA) 31.8  (10.59) 31.0  (10.77) 31.4  (10.65)
[1]
Did not participate in the Induction Phase. Please see Maintenance Phase.
[2]
Did not participate in the Maintenance Phase. Please see Induction Phase.
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 185 participants 185 participants 116 participants 111 participants 597 participants
Induction Phase - Female 156 157 0 0 313
Induction Phase - Male 29 28 0 0 57
Maintenance Phase - Female 0 0 99 96 195
Maintenance Phase - Male 0 0 17 15 32
1.Primary Outcome
Title Induction Phase: Number of Patients Showing Treatment Response
Hide Description Treatment response was adjudicated by a blinded clinical endpoints committee (CEC) and defined as: a) Decrease in proteinuria, defined as a decrease in the urine protein to creatinine ratio (UPCr) to <3 in subjects with baseline proteinuria ≥3 UPCr or a decrease in the UPCr by ≥50% in subjects with proteinuria <3 UPCr at Baseline, and b) Stabilization of serum creatinine or improvement. UPCr were derived from the 24 hour urine collection. Patients who did not show a treatment response at Week 24 or who withdrew earlier than Week 24 were considered non-responders.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population was intent to treat which comprised all subjects who were randomized into the study and had at least one post-baseline efficacy assessment.
Arm/Group Title Intravenous Cyclophosphamide Mycophenolate Mofetil
Hide Arm/Group Description:
Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Overall Number of Participants Analyzed 185 185
Measure Type: Number
Unit of Measure: participants
Responder 98 104
Non-responder 87 81
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intravenous Cyclophosphamide, Mycophenolate Mofetil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.478
Comments [Not Specified]
Method Regression, Logistic
Comments Covariates included Treatment, Race, Geographical Region, and WHO Lupus Nephritis Class V and specified interaction terms.
2.Primary Outcome
Title Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval
Hide Description Treatment Failure was adjudicated by a clinical endpoints committee and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to treatment failure for each patient. The data presented are the percentage of participants who were treatment-failure free at each time interval as estimated by Kaplan-Meier.
Time Frame From the start of the Maintenance Phase to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat analysis population which consisted of all subjects who were randomized to the maintenance phase of the study and had at least 1 maintenance efficacy assessment.
Arm/Group Title Mycophenolate Mofetil Azathioprine
Hide Arm/Group Description:
Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.
Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Overall Number of Participants Analyzed 116 111
Measure Type: Number
Unit of Measure: Percentage of participants
Start of Maintenance Phase to Month 3 98.2 97.2
Month 3 to Month 6 93.7 89.3
Month 6 to Month 9 89.9 86.2
Month 9 to Month 12 86.0 83.0
Month 12 to Month 15 86.0 77.5
Month 15 to Month 18 84.9 74.1
Month 18 to Month 21 84.9 70.7
Month 21 to Month 24 83.9 68.3
Month 24 to Month 27 82.8 67.1
Month 27 to Month 30 82.8 65.9
Month 30 to Month 33 81.7 63.4
Month 33 to Month 36 81.7 58.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mycophenolate Mofetil, Azathioprine
Comments The difference in Kaplan-Meier survival curves between treatment groups (MMF−AZA) was assessed using a log-rank test, which is a non-parametric test to compare the survival distributions of two groups commonly used to analyze time-to-event endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Testing at the alpha=0.05 level was applied with no adjustments made for multiplicity.
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Induction Phase: Number of Participants Achieving Complete Remission
Hide Description Number of participants achieving complete remission as defined by return to normal serum creatinine, proteinuria ≤500 mg/24 hours and an inactive urinary sediment (absence of red blood cells, white blood cells or cellular or granular casts) after 24 weeks.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population was intent to treat.
Arm/Group Title Intravenous Cyclophosphamide Mycophenolate Mofetil
Hide Arm/Group Description:
Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Overall Number of Participants Analyzed 185 185
Measure Type: Number
Unit of Measure: participants
Complete Remission - Yes 15 16
Complete Remission - No 170 169
4.Secondary Outcome
Title Induction Phase: Change From Baseline to Week 24 in Serum Creatinine
Hide Description [Not Specified]
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population was intent to treat. The analysis included only those patients for whom data was available at both time points, as indicated by "n".
Arm/Group Title Intravenous Cyclophosphamide Mycophenolate Mofetil
Hide Arm/Group Description:
Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Overall Number of Participants Analyzed 185 185
Mean (Standard Deviation)
Unit of Measure: µmol/L
Baseline [n= 184, 185] 92.7  (56.88) 108.6  (97.21)
Week 24 [n= 155, 151] 83.5  (56.26) 77.6  (35.08)
Change from Baseline to Week 24 [n= 154, 151] -5.1  (45.96) -18.9  (59.03)
5.Secondary Outcome
Title Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein
Hide Description 24-hour urine protein was measured at Baseline and Week 24.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population was intent to treat. The analysis included only those patients for whom data was available at both time points, as indicated by "n".
Arm/Group Title Intravenous Cyclophosphamide Mycophenolate Mofetil
Hide Arm/Group Description:
Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Overall Number of Participants Analyzed 185 185
Mean (Standard Deviation)
Unit of Measure: mg/day
Baseline [n=180, 180] 4451.4  (3506.59) 4208.9  (3347.34)
Week 24 [n= 150, 144] 1831.6  (2413.84) 1599.0  (2165.80)
Change from Baseline to Week 24 [n= 146, 142] -2513.7  (3223.68) -2510.6  (3132.69)
6.Secondary Outcome
Title Induction Phase: Change From Baseline to Week 24 in Serum Albumin
Hide Description [Not Specified]
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population was intent to treat. The analysis included only those patients for whom data was available at both time points, as indicated by "n".
Arm/Group Title Intravenous Cyclophosphamide Mycophenolate Mofetil
Hide Arm/Group Description:
Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Overall Number of Participants Analyzed 185 185
Mean (Standard Deviation)
Unit of Measure: g/L
Baseline [n=184, 185] 28.6  (6.98) 30.5  (6.90)
Week 24 [n=155, 151] 38.3  (6.16) 38.4  (5.50)
Change from Baseline to Week 24 [n=154, 151] 9.0  (6.77) 7.5  (6.25)
7.Secondary Outcome
Title Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score
Hide Description

BILAG indices provide a scoring system for the assessment of lupus disease activity in terms of the need for steroid treatment in 8 organs/systems. Eighty-six items were scored resulting in a classification of A (severe activity), B (moderate activity), C (mild activity), D (no current activity) and E (no activity ever observed) for each organ system. The BILAG individual system summaries were calculated by a program supplied by ADS-Limathon (Sheffield, UK).

The score at baseline was compared to the score at the 24 week endpoint for each treatment group, reported here for the renal system.

Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population was intent to treat. The endpoint was defined using the last observation carried forward approach. If no post-Baseline value was available, endpoint was considered missing.
Arm/Group Title Intravenous Cyclophosphamide Mycophenolate Mofetil
Hide Arm/Group Description:
Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Overall Number of Participants Analyzed 181 181
Measure Type: Number
Unit of Measure: Percentage of participants
Shift from Baseline=A to 24 Week Endpoint=A 27.1 17.1
Shift from Baseline=A to 24 Week Endpoint=B 34.8 39.2
Shift from Baseline=A to 24 Week Endpoint=C 24.9 33.1
Shift from Baseline=A to 24 Week Endpoint=D 9.4 5.5
Shift from Baseline=B to 24 Week Endpoint=A 0.0 0.0
Shift from Baseline=B to 24 Week Endpoint=B 1.1 1.7
Shift from Baseline=B to 24 Week Endpoint=C 1.7 2.2
Shift from Baseline=B to 24 Week Endpoint=D 0.0 1.1
Shift from Baseline=C to 24 Week Endpoint=A 0.0 0.0
Shift from Baseline=C to 24 Week Endpoint=B 0.6 0.0
Shift from Baseline=C to 24 Week Endpoint=C 0.0 0.0
Shift from Baseline=C to 24 Week Endpoint=D 0.0 0.0
Shift from Baseline=D to 24 Week Endpoint=A 0.0 0.0
Shift from Baseline=D to 24 Week Endpoint=B 0.0 0.0
Shift from Baseline=D to 24 Week Endpoint=C 0.6 0.0
Shift from Baseline=D to 24 Week Endpoint=D 0.0 0.0
8.Secondary Outcome
Title Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores
Hide Description The SF-36 is a 36 item quality of life questionnaire. The short-form version has eleven questions that permit the participant to rate how they feel that particular day. The SF-36 consists of eight scaled scores and two component scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 score with the higher scores indicating better quality of life.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population is intention to treat. The analysis included only those patients for whom data was available at both time points, as indicated by "n".
Arm/Group Title Intravenous Cyclophosphamide Mycophenolate Mofetil
Hide Arm/Group Description:
Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Overall Number of Participants Analyzed 185 185
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Physical Component Summary [n=139, 137] 6.4  (8.74) 5.2  (8.60)
Mental Component Summary [n=139, 137] 5.7  (11.39) 6.7  (11.45)
Bodily Pain Score [n=141, 137] 16.8  (25.85) 13.4  (24.57)
General Health Score [n=139, 137] 11.5  (20.90) 9.1  (19.49)
Mental Health Score [n=141, 137] 9.8  (19.47) 9.3  (18.96)
Physical functioning Score [n=141, 137] 9.3  (24.63) 11.6  (23.12)
Role-Emotional Score [n=141, 137] 18.4  (46.71) 23.4  (44.90)
Role-Physical Score [n=141, 137] 34.0  (47.65) 28.6  (48.18)
Social Function Score [n=141, 137] 18.2  (29.26) 17.7  (28.06)
Vitality Score [n=141, 137] 11.6  (20.68) 14.2  (23.30)
9.Secondary Outcome
Title Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Deaths
Hide Description Treatment Failure was adjudicated by a clinical endpoints committee (CEC) and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis (LN).
Time Frame From the start of the Maintenance Phase to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase intent to treat population.
Arm/Group Title Mycophenolate Mofetil (MMF) Azathioprine (AZA)
Hide Arm/Group Description:
Mycophenolate mofetil (MMF) 1.0 g orally twice a day + Placebo to Azathioprine orally once a day + Corticosteroid for 36 months
Azathioprine (AZA) 2 mg/kg/day orally once a day + Placebo to MMF orally twice a day + Corticosteroid for 36 months.
Overall Number of Participants Analyzed 116 111
Measure Type: Number
Unit of Measure: Deaths
0 1
10.Secondary Outcome
Title Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With End-stage Renal Disease (ESRD)
Hide Description Time to treatment failure, adjudicated by the Clinical Endpoints Committee (CEC), was defined as any 1 the following: death, ESRD, sustained doubling of serum creatinine, renal flare (proteinuric or nephritic), or requirement for rescue therapy to treat deterioration or exacerbation of Lupus nephritis. ESRD is defined as progression to chronic hemodialysis or renal transplant.
Time Frame From the start of the Maintenance Phase to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase intent to treat population. The analysis includes all event data, regardless of whether or not the event was the earliest Clinical Endpoints Committee-adjudicated reason for treatment failure.
Arm/Group Title Mycophenolate Mofetil (MMF) Azathioprine (AZA)
Hide Arm/Group Description:
Mycophenolate mofetil (MMF) 1.0 g twice daily (BID) along with placebo matching AZA (2.0 mg/kg/day), plus corticosteroid, until 36 months of therapy.
Azathioprine (AZA) 2.0 mg/kg/day along with placebo matching MMF (1.0 g BID), plus corticosteroid for 36 months of therapy
Overall Number of Participants Analyzed 116 111
Measure Type: Number
Unit of Measure: participants
0 3
11.Secondary Outcome
Title Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With Sustained Doubling of Serum Creatinine
Hide Description Sustained doubling of serum creatinine concentration is defined as the first serum creatinine value that is twice the mean of the lowest 2 values from screening to end of induction, as confirmed by a second serum creatinine value obtained at least 4 weeks after the initial doubling.
Time Frame From the start of the Maintenance Phase to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase intent to treat population. The analysis includes all event data, regardless of whether or not the event was the earliest Clinical Endpoints Committee-adjudicated reason for treatment failure.
Arm/Group Title Mycophenolate Mofetil Azathioprine
Hide Arm/Group Description:
Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.
Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Overall Number of Participants Analyzed 116 111
Measure Type: Number
Unit of Measure: participants
1 5
12.Secondary Outcome
Title Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval
Hide Description A proteinuric flare is defined as a doubling of the urine protein:creatinine ratio, and proteinuria ≥1 g/24 h in patients with urine protein ≤0.5 g/24 h at the end of the induction phase, or proteinuria ≥2 g/24 h if urine protein was >0.5 g/24 h at the end of the induction phase. A nephritic flare is defined as a 25% increase in serum creatinine accompanied by 1 or more of the following: (a) simultaneous doubling of the proteinuria reaching a minimum of 2 g/24 h (b) new/increased hematuria or (c) the appearance of cellular casts. All flares were adjudicated by a clinical endpoints committee.
Time Frame From the start of the Maintenance Phase to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase intent to treat population. The analysis includes all event data, regardless of whether or not the event was the earliest Clinical Endpoints Committee-adjudicated reason for treatment failure.
Arm/Group Title Mycophenolate Mofetil Azathioprine
Hide Arm/Group Description:
Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.
Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Overall Number of Participants Analyzed 116 111
Measure Type: Number
Unit of Measure: Percentage of participants
Start of Maintenance Phase to Month 3 98.2 97.2
Month 3 to Month 6 94.6 90.3
Month 6 to Month 9 90.8 87.2
Month 9 to Month 12 87.8 85.0
Month 12 to Month 15 87.8 82.8
Month 15 to Month 18 86.8 79.2
Month 18 to Month 21 86.8 78.0
Month 21 to Month 24 86.8 75.5
Month 24 to Month 27 86.8 74.2
Month 27 to Month 30 86.8 74.2
Month 30 to Month 33 85.6 72.9
Month 33 to Month 36 85.6 70.1
13.Secondary Outcome
Title Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy
Hide Description The primary efficacy parameter was the time to treatment failure, adjudicated by the Clinical Endpoints Committee (CEC), defined as any of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or requirement for rescue therapy to treat deterioration or exacerbation of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to rescue treatment for each patient. The data presented are the percentage of participants who were rescue treatment free at each time interval as estimated by Kaplan-Meier.
Time Frame From the start of the Maintenance Phase to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase intent to treat population. The analysis includes all event data, regardless of whether or not the event was the earliest Clinical Endpoints Committee-adjudicated reason for treatment failure.
Arm/Group Title Mycophenolate Mofetil Azathioprine
Hide Arm/Group Description:
Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.
Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Overall Number of Participants Analyzed 116 111
Measure Type: Number
Unit of Measure: Percentage of participants
Start of Maintenance Phase to Month 3 100 99.1
Month 3 to Month 6 98.2 95.1
Month 6 to Month 9 97.2 93.0
Month 9 to Month 12 94.2 91.9
Month 12 to Month 15 94.2 88.4
Month 15 to Month 18 94.2 87.1
Month 18 to Month 21 93.1 83.1
Month 21 to Month 24 91.9 83.1
Month 24 to Month 27 90.8 81.7
Month 27 to Month 30 90.8 80.3
Month 30 to Month 33 90.8 78.8
Month 33 to Month 36 90.8 75.9
14.Secondary Outcome
Title Maintenance Phase: Participants With Major Extra-renal Flare
Hide Description A major extra-renal flare is defined as a British Isles Lupus Assessment Group (BILAG) Score category A in one extrarenal organ or three organs with concurrent category B scores. BILAG indices provide a scoring system for the assessment of lupus disease activity in terms of the need for steroid treatment in 8 organs/systems. Eighty-six items were scored resulting in a classification of A (severe activity), B (moderate activity), C (mild activity), D (no current activity) and E (no activity ever observed) for each organ system.
Time Frame From the start of the Maintenance Phase to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase intent to treat population.
Arm/Group Title Mycophenolate Mofetil Azathioprine
Hide Arm/Group Description:
Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.
Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Overall Number of Participants Analyzed 116 111
Measure Type: Number
Unit of Measure: participants
7 6
Time Frame AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months).
Adverse Event Reporting Description The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
 
Arm/Group Title Induction Phase: Cyclophosphamide Induction Phase: Mycophenolate Mofetil Maintenance Phase: Mycophenolate Mofetil Maintenance Phase: Azathioprine
Hide Arm/Group Description Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase. Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase. Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase. Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
All-Cause Mortality
Induction Phase: Cyclophosphamide Induction Phase: Mycophenolate Mofetil Maintenance Phase: Mycophenolate Mofetil Maintenance Phase: Azathioprine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Induction Phase: Cyclophosphamide Induction Phase: Mycophenolate Mofetil Maintenance Phase: Mycophenolate Mofetil Maintenance Phase: Azathioprine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   41/180 (22.78%)   51/184 (27.72%)   27/115 (23.48%)   37/111 (33.33%) 
Blood and lymphatic system disorders         
Anaemia  1  1/180 (0.56%)  2/184 (1.09%)  1/115 (0.87%)  0/111 (0.00%) 
Leukopenia  1  2/180 (1.11%)  1/184 (0.54%)  0/115 (0.00%)  4/111 (3.60%) 
Neutropenia  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Thrombotic thrombocytopenic purpura  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Thrombocytopenia  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Febrile neutropenia  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Cardiac disorders         
Acute coronary syndrome  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Myocardial infarction  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Cardiac arrest  1  1/180 (0.56%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Pericardial effusion  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Acute myocardial infarction  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Pericarditis  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Ear and labyrinth disorders         
Deafness neurosensory  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  0/180 (0.00%)  3/184 (1.63%)  1/115 (0.87%)  0/111 (0.00%) 
Vomiting  1  1/180 (0.56%)  2/184 (1.09%)  0/115 (0.00%)  0/111 (0.00%) 
Dyspepsia  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Abdominal pain  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  1/111 (0.90%) 
Gastrooesophageal reflux disease  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Abdominal distension  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Gingivitis  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Pancreatitis  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Gastritis  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
General disorders         
Death  1  1/180 (0.56%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Pyrexia  1  3/180 (1.67%)  1/184 (0.54%)  1/115 (0.87%)  0/111 (0.00%) 
Oedema  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Non-cardiac chest pain  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  1/111 (0.90%) 
Chest pain  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Hepatobiliary disorders         
Hepatic function abnormal  1  1/180 (0.56%)  0/184 (0.00%)  1/115 (0.87%)  1/111 (0.90%) 
Cholecystitis acute  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  1/111 (0.90%) 
Immune system disorders         
Anaphylactic reaction  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Infections and infestations         
Pneumonia  1  3/180 (1.67%)  5/184 (2.72%)  2/115 (1.74%)  1/111 (0.90%) 
Bronchitis  1  1/180 (0.56%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Bronchopneumonia  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Lung infection  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Lobar pneumonia  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Herpes zoster  1  2/180 (1.11%)  5/184 (2.72%)  1/115 (0.87%)  1/111 (0.90%) 
Herpes simplex  1  1/180 (0.56%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Septic shock  1  0/180 (0.00%)  2/184 (1.09%)  0/115 (0.00%)  0/111 (0.00%) 
Acinetobacter bacteraemia  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Meningitis tuberculous  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Pulmonary tuberculosis  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Tuberculosis gastrointestinal  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Gastroenteritis  1  0/180 (0.00%)  1/184 (0.54%)  1/115 (0.87%)  0/111 (0.00%) 
Retroperitoneal abscess  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Gastrointestinal infection  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Skin infection  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Subcutaneous abscess  1  0/180 (0.00%)  1/184 (0.54%)  1/115 (0.87%)  0/111 (0.00%) 
Fungaemia  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Respiratory tract infection  1  2/180 (1.11%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Infection  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Meningitis streptococcal  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Viral infection  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Gastroenteritis viral  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Cellulitis  1  2/180 (1.11%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Meningitis bacterial  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Subacute endocarditis  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Tonsillitis  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Upper respiratory tract infection  1  4/180 (2.22%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Osteomyelitis  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Wound infection  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Influenza  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Urosepsis  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Disseminated tuberculosis  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Pyelonephritis  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Appendicitis  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  2/111 (1.80%) 
Peridiverticulitis  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Sepsis  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Cystitis  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Genitourinary tract infection  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Pneumonia bacterial  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Tubo-ovarian abscess  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Viral upper respiratory tract infection  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Injury, poisoning and procedural complications         
Overdose  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  1/111 (0.90%) 
Head injury  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Hip fracture  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Foot fracture  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Road traffic accident  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Traumatic hematoma  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Wrist fracture  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Investigations         
Platelet count decreased  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
White blood cell count decreased  1  1/180 (0.56%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
International normalised ratio increased  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Alanine aminotransferase increased  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Blood creatinine increased  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Biopsy kidney  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Metabolism and nutrition disorders         
Hypokalaemia  1  0/180 (0.00%)  2/184 (1.09%)  0/115 (0.00%)  0/111 (0.00%) 
Hyperkalaemia  1  1/180 (0.56%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Diabetes mellitus  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Dehydration  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Fluid overload  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  1/111 (0.90%) 
Hypoalbuminaemia  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Musculoskeletal and connective tissue disorders         
Systemic lupus erythematosus  1  4/180 (2.22%)  2/184 (1.09%)  3/115 (2.61%)  2/111 (1.80%) 
Arthralgia  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Pain in extremity  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Costochondritis  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Myositis  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Osteonecrosis  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Rhabdomyolysis  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Ovarian germ cell teratoma benign  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Uterine leiomyoma  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Uterine carcinoma in situ  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Nervous system disorders         
Headache  1  0/180 (0.00%)  1/184 (0.54%)  1/115 (0.87%)  1/111 (0.90%) 
Brain oedema  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Cerebrovascular accident  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Syncope  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Lupus encephalitis  1  2/180 (1.11%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Convulsion  1  3/180 (1.67%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Cerebral infarction  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Tremor  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Superior sagittal sinus thrombosis  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Pregnancy, puerperium and perinatal conditions         
Pregnancy  1  0/180 (0.00%)  2/184 (1.09%)  3/115 (2.61%)  6/111 (5.41%) 
Pre-eclampsia  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  1/111 (0.90%) 
Premature baby  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Psychiatric disorders         
Depression  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Psychotic disorder  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Abnormal behavior  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Major depression  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Panic attack  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Suicidal ideation  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Renal and urinary disorders         
Renal failure acute  1  0/180 (0.00%)  3/184 (1.63%)  0/115 (0.00%)  1/111 (0.90%) 
Renal failure  1  1/180 (0.56%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Renal impairment  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  1/111 (0.90%) 
Renal failure chronic  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Lupus nephritis  1  0/180 (0.00%)  2/184 (1.09%)  1/115 (0.87%)  5/111 (4.50%) 
Proteinuria  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Nephrotic syndrome  1  2/180 (1.11%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Hematuria  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Renal colic  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Reproductive system and breast disorders         
Uterine haemorrhage  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Cervical dysplasia  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Menometrorrhagia  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Ovarian hemorrhage  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Haemoptysis  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Pulmonary haemorrhage  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Interstitial lung disease  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Pulmonary embolism  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  1/111 (0.90%) 
Respiratory failure  1  0/180 (0.00%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Lupus pneumonitis  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Pharyngolaryngeal pain  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Pulmonary hypertension  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Skin and subcutaneous tissue disorders         
Dermatitis exfoliative  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Panniculitis  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Rash maculo-papular  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Angioedema  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Surgical and medical procedures         
Abortion induced  1  0/180 (0.00%)  0/184 (0.00%)  2/115 (1.74%)  4/111 (3.60%) 
Vascular disorders         
Deep vein thrombosis  1  1/180 (0.56%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Hypertension  1  1/180 (0.56%)  1/184 (0.54%)  0/115 (0.00%)  0/111 (0.00%) 
Venous stenosis  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Subclavian vein thrombosis  1  1/180 (0.56%)  0/184 (0.00%)  0/115 (0.00%)  0/111 (0.00%) 
Peripheral ischemia  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  0/111 (0.00%) 
Thrombosis  1  0/180 (0.00%)  0/184 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Induction Phase: Cyclophosphamide Induction Phase: Mycophenolate Mofetil Maintenance Phase: Mycophenolate Mofetil Maintenance Phase: Azathioprine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   171/180 (95.00%)   177/184 (96.20%)   113/115 (98.26%)   108/111 (97.30%) 
Blood and lymphatic system disorders         
Anaemia  1  12/180 (6.67%)  23/184 (12.50%)  13/115 (11.30%)  17/111 (15.32%) 
Leukopenia  1  38/180 (21.11%)  11/184 (5.98%)  26/115 (22.61%)  40/111 (36.04%) 
Neutropenia  1  12/180 (6.67%)  3/184 (1.63%)  0/115 (0.00%)  0/111 (0.00%) 
Cardiac disorders         
Palpitations  1  6/180 (3.33%)  11/184 (5.98%)  0/115 (0.00%)  0/111 (0.00%) 
Tachycardia  1  6/180 (3.33%)  10/184 (5.43%)  0/115 (0.00%)  0/111 (0.00%) 
Endocrine disorders         
Cushingoid  1  11/180 (6.11%)  9/184 (4.89%)  0/115 (0.00%)  0/111 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  23/180 (12.78%)  52/184 (28.26%)  22/115 (19.13%)  20/111 (18.02%) 
Nausea  1  82/180 (45.56%)  27/184 (14.67%)  20/115 (17.39%)  21/111 (18.92%) 
Vomiting  1  68/180 (37.78%)  25/184 (13.59%)  14/115 (12.17%)  18/111 (16.22%) 
Abdominal pain  1  13/180 (7.22%)  19/184 (10.33%)  11/115 (9.57%)  14/111 (12.61%) 
Abdominal pain upper  1  18/180 (10.00%)  15/184 (8.15%)  13/115 (11.30%)  11/111 (9.91%) 
Constipation  1  9/180 (5.00%)  12/184 (6.52%)  0/115 (0.00%)  0/111 (0.00%) 
Dyspepsia  1  5/180 (2.78%)  10/184 (5.43%)  3/115 (2.61%)  7/111 (6.31%) 
Gastritis  1  0/180 (0.00%)  0/184 (0.00%)  11/115 (9.57%)  7/111 (6.31%) 
Mouth ulceration  1  0/180 (0.00%)  0/184 (0.00%)  8/115 (6.96%)  4/111 (3.60%) 
Toothache  1  0/180 (0.00%)  0/184 (0.00%)  5/115 (4.35%)  9/111 (8.11%) 
General disorders         
Oedema peripheral  1  30/180 (16.67%)  35/184 (19.02%)  8/115 (6.96%)  7/111 (6.31%) 
Oedema  1  17/180 (9.44%)  11/184 (5.98%)  0/115 (0.00%)  0/111 (0.00%) 
Fatigue  1  18/180 (10.00%)  18/184 (9.78%)  17/115 (14.78%)  20/111 (18.02%) 
Asthenia  1  15/180 (8.33%)  9/184 (4.89%)  6/115 (5.22%)  6/111 (5.41%) 
Chest pain  1  10/180 (5.56%)  8/184 (4.35%)  0/115 (0.00%)  0/111 (0.00%) 
Pyrexia  1  30/180 (16.67%)  12/184 (6.52%)  0/115 (0.00%)  0/111 (0.00%) 
Hepatobiliary disorders         
Hepatic function abnormal  1  0/180 (0.00%)  0/184 (0.00%)  4/115 (3.48%)  6/111 (5.41%) 
Infections and infestations         
Nasopharyngitis  1  29/180 (16.11%)  25/184 (13.59%)  15/115 (13.04%)  13/111 (11.71%) 
Upper respiratory tract infection  1  28/180 (15.56%)  17/184 (9.24%)  41/115 (35.65%)  36/111 (32.43%) 
Herpes zoster  1  6/180 (3.33%)  14/184 (7.61%)  7/115 (6.09%)  6/111 (5.41%) 
Urinary tract infection  1  17/180 (9.44%)  19/184 (10.33%)  20/115 (17.39%)  27/111 (24.32%) 
Sinusitis  1  0/180 (0.00%)  0/184 (0.00%)  10/115 (8.70%)  4/111 (3.60%) 
Pharyngitis  1  0/180 (0.00%)  0/184 (0.00%)  6/115 (5.22%)  6/111 (5.41%) 
Bronchitis  1  0/180 (0.00%)  0/184 (0.00%)  14/115 (12.17%)  7/111 (6.31%) 
Gastroenteritis  1  0/180 (0.00%)  0/184 (0.00%)  16/115 (13.91%)  6/111 (5.41%) 
Influenza  1  0/180 (0.00%)  0/184 (0.00%)  13/115 (11.30%)  14/111 (12.61%) 
Respiratory tract infection  1  0/180 (0.00%)  0/184 (0.00%)  7/115 (6.09%)  3/111 (2.70%) 
Investigations         
White blood cell count decreased  1  16/180 (8.89%)  5/184 (2.72%)  0/115 (0.00%)  0/111 (0.00%) 
Metabolism and nutrition disorders         
Hypokalaemia  1  3/180 (1.67%)  13/184 (7.07%)  6/115 (5.22%)  1/111 (0.90%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  43/180 (23.89%)  29/184 (15.76%)  29/115 (25.22%)  32/111 (28.83%) 
Back pain  1  16/180 (8.89%)  19/184 (10.33%)  13/115 (11.30%)  13/111 (11.71%) 
Pain in extremity  1  9/180 (5.00%)  6/184 (3.26%)  10/115 (8.70%)  9/111 (8.11%) 
Arthritis  1  10/180 (5.56%)  4/184 (2.17%)  8/115 (6.96%)  11/111 (9.91%) 
Musculoskeletal pain  1  0/180 (0.00%)  0/184 (0.00%)  6/115 (5.22%)  1/111 (0.90%) 
Myalgia  1  0/180 (0.00%)  0/184 (0.00%)  7/115 (6.09%)  5/111 (4.50%) 
Systemic lupus erythematosus  1  0/180 (0.00%)  0/184 (0.00%)  6/115 (5.22%)  15/111 (13.51%) 
Muscle spasms  1  0/180 (0.00%)  0/184 (0.00%)  1/115 (0.87%)  6/111 (5.41%) 
Nervous system disorders         
Headache  1  47/180 (26.11%)  38/184 (20.65%)  25/115 (21.74%)  27/111 (24.32%) 
Dizziness  1  10/180 (5.56%)  8/184 (4.35%)  5/115 (4.35%)  10/111 (9.01%) 
Pregnancy, puerperium and perinatal conditions         
Pregnancy  1  0/180 (0.00%)  0/184 (0.00%)  3/115 (2.61%)  6/111 (5.41%) 
Psychiatric disorders         
Insomnia  1  11/180 (6.11%)  10/184 (5.43%)  11/115 (9.57%)  3/111 (2.70%) 
Renal and urinary disorders         
Lupus nephritis  1  0/180 (0.00%)  0/184 (0.00%)  17/115 (14.78%)  25/111 (22.52%) 
Proteinuria  1  0/180 (0.00%)  0/184 (0.00%)  11/115 (9.57%)  4/111 (3.60%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  16/180 (8.89%)  24/184 (13.04%)  16/115 (13.91%)  14/111 (12.61%) 
Dyspnoea  1  6/180 (3.33%)  10/184 (5.43%)  4/115 (3.48%)  6/111 (5.41%) 
Oropharyngeal pain  1  0/180 (0.00%)  0/184 (0.00%)  5/115 (4.35%)  7/111 (6.31%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  64/180 (35.56%)  20/184 (10.87%)  12/115 (10.43%)  11/111 (9.91%) 
Rash  1  21/180 (11.67%)  19/184 (10.33%)  15/115 (13.04%)  14/111 (12.61%) 
Acne  1  9/180 (5.00%)  9/184 (4.89%)  0/115 (0.00%)  0/111 (0.00%) 
Erythema  1  10/180 (5.56%)  5/184 (2.72%)  0/115 (0.00%)  0/111 (0.00%) 
Butterfly rash  1  0/180 (0.00%)  0/184 (0.00%)  7/115 (6.09%)  11/111 (9.91%) 
Skin lesion  1  0/180 (0.00%)  0/184 (0.00%)  6/115 (5.22%)  4/111 (3.60%) 
Pruritus  1  0/180 (0.00%)  0/184 (0.00%)  2/115 (1.74%)  8/111 (7.21%) 
Vascular disorders         
Hypertension  1  25/180 (13.89%)  26/184 (14.13%)  8/115 (6.96%)  7/111 (6.31%) 
Raynaud's phenomenon  1  0/180 (0.00%)  0/184 (0.00%)  3/115 (2.61%)  9/111 (8.11%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.1)
For many of the Maintenance Phase Outcomes, the total number of events precluded a meaningful time to event statistical analysis, therefore, only events numbers are reported.
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.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffman-LaRoche
Phone: 800-821-8590
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00377637    
Obsolete Identifiers: NCT00121082
Other Study ID Numbers: WX17801
First Submitted: September 15, 2006
First Posted: September 18, 2006
Results First Submitted: August 11, 2011
Results First Posted: December 6, 2011
Last Update Posted: December 6, 2011