A Study of Mycophenolate Mofetil (CellCept) in Management of Patients With Lupus Nephritis.
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT00377637
Collaborator
Aspreva Pharmaceuticals (Industry)
370
108
4
56
3.4
0.1
Study Details
Study Description
Brief Summary
This 2 arm study assessed the efficacy of Mycophenolate Mofetil (MMF; CellCept) compared to cyclophosphamide in inducing a response in patients with lupus nephritis, and the long term efficacy of MMF compared to azathioprine in maintaining remission and renal function. Patients were randomized to receive either MMF (1.5 g twice daily [bid]) or cyclophosphamide (0.5-1.0 g/m^2 in monthly pulses) in the induction phase. Those patients meeting criteria for response were re-randomized for entry into the maintenance phase, to receive either MMF (1 g bid) or azathioprine (2 mg/kg/day).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
370 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Prospective, Randomized, Active Controlled, Parallel Group, Multi-center Trial to Assess the Efficacy and Safety of Mycophenolate Mofetil (MMF) in Inducing Response and Maintaining Remission in Subjects With Lupus Nephritis.
Study Start Date
:
Jul 1, 2005
Actual Primary Completion Date
:
Mar 1, 2007
Actual Study Completion Date
:
Mar 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Induction Phase: Mycophenolate mofetil Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24 weeks of the Induction Phase. |
Drug: Mycophenolate mofetil (MMF)
Supplied as 500 mg tablets taken orally twice a day (BID). Dose specific for each arm. Dosing started at 500 mg BID for the first week, increasing by 500 mg in subsequent weeks until the final target dose was reached.
Other Names:
Drug: Corticosteroid
Oral prednisolone (or equivalent) starting at a dose of 0.75-1.0 mg/kg/day (maximum 60 mg/day) tapered to 10 mg/day.
|
| Active Comparator: Induction Phase: Cyclophosphamide Participants received monthly 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. |
Drug: Cyclophosphamide
Intravenous cyclophosphamide (IVC) was administered every four weeks (monthly) to a total of six infusions.
Dosing was started at 0.75 g/m^2 of body surface area for the first month, with subsequent doses at 0.5-1.0 g/m^2. The target dose was 1.0 g/m^2, but doses were titrated by 0.25 g/m^2 increments to maintain nadir leukocyte count between 2500-4000/mm^3.
Other Names:
Drug: Corticosteroid
Oral prednisolone (or equivalent) starting at a dose of 0.75-1.0 mg/kg/day (maximum 60 mg/day) tapered to 10 mg/day.
|
| Experimental: Maintenance Phase: Mycophenolate mofetil Participants 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. |
Drug: Mycophenolate mofetil (MMF)
Supplied as 500 mg tablets taken orally twice a day (BID). Dose specific for each arm. Dosing started at 500 mg BID for the first week, increasing by 500 mg in subsequent weeks until the final target dose was reached.
Other Names:
Drug: Placebo to Azathioprine
Placebo capsules matching Azathioprine taken orally once a day.
Drug: Corticosteroid
Oral prednisolone (or equivalent) starting at a dose of 0.75-1.0 mg/kg/day (maximum 60 mg/day) tapered to 10 mg/day.
|
| Active Comparator: Maintenance Phase: Azathioprine Participants 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. |
Drug: Azathioprine
2 mg/kg/day orally, provided as 50 mg capsules to be taken after meals.
Other Names:
Drug: Placebo to Mycophenolate mofetil
Placebo tablets matching Mycophenolate mofetil taken orally twice daily.
Drug: Corticosteroid
Oral prednisolone (or equivalent) starting at a dose of 0.75-1.0 mg/kg/day (maximum 60 mg/day) tapered to 10 mg/day.
|
Outcome Measures
Primary Outcome Measures
- Induction Phase: Number of Patients Showing Treatment Response [24 weeks]
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.
- Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval [From the start of the Maintenance Phase to Month 36]
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.
Secondary Outcome Measures
- Induction Phase: Number of Participants Achieving Complete Remission [24 weeks]
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.
- Induction Phase: Change From Baseline to Week 24 in Serum Creatinine [Baseline, Week 24]
- Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein [Baseline, Week 24]
24-hour urine protein was measured at Baseline and Week 24.
- Induction Phase: Change From Baseline to Week 24 in Serum Albumin [Baseline, Week 24]
- Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score [Baseline, 24 weeks]
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.
- Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores [Baseline and 24 weeks]
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.
- Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Deaths [From the start of the Maintenance Phase to Month 36]
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).
- Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With End-stage Renal Disease (ESRD) [From the start of the Maintenance Phase to Month 36]
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.
- Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With Sustained Doubling of Serum Creatinine [From the start of the Maintenance Phase to Month 36]
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.
- Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval [From the start of the Maintenance Phase to Month 36]
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.
- Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy [From the start of the Maintenance Phase to Month 36]
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.
- Maintenance Phase: Participants With Major Extra-renal Flare [From the start of the Maintenance Phase to Month 36]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
male or female patients, 12-75 years of age;
-
diagnosis of systemic lupus erythematosus;
-
kidney biopsy within 6 months of study, with histological diagnosis of lupus nephritis;
-
laboratory evidence of active nephritis.
Exclusion Criteria:
-
continuous dialysis starting >2 weeks before randomization into induction phase, and/or with an anticipated duration of >8 weeks;
-
previous or planned kidney transplant;
-
other clinically significant active medical conditions.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Huntsville | Alabama | United States | 35801 | |
| 2 | La Jolla | California | United States | 92037 | |
| 3 | Los Angeles | California | United States | 90095 | |
| 4 | San Francisco | California | United States | 94143 | |
| 5 | San Leandro | California | United States | 94578 | |
| 6 | Torrance | California | United States | 90502 | |
| 7 | Miami | Florida | United States | 33136 | |
| 8 | Atlanta | Georgia | United States | 30303 | |
| 9 | Chicago | Illinois | United States | 60611 | |
| 10 | Chicago | Illinois | United States | 60637 | |
| 11 | Baltimore | Maryland | United States | 21205 | |
| 12 | Boston | Massachusetts | United States | 02115 | |
| 13 | Ann Arbor | Michigan | United States | 48109-0358 | |
| 14 | Columbia | Missouri | United States | 65212 | |
| 15 | Brooklyn | New York | United States | 11203 | |
| 16 | Lake Success | New York | United States | 11042 | |
| 17 | New York | New York | United States | 10003 | |
| 18 | New York | New York | United States | 10021 | |
| 19 | New York | New York | United States | 10032 | |
| 20 | Chapel Hill | North Carolina | United States | 27599-7280 | |
| 21 | Durham | North Carolina | United States | 27710 | |
| 22 | Cleveland | Ohio | United States | 44136 | |
| 23 | Columbus | Ohio | United States | 43210 | |
| 24 | Oklahoma City | Oklahoma | United States | 73104 | |
| 25 | Philadelphia | Pennsylvania | United States | 19104 | |
| 26 | Pittsburgh | Pennsylvania | United States | 15213 | |
| 27 | Charleston | South Carolina | United States | 29425 | |
| 28 | Dallas | Texas | United States | 75390 | |
| 29 | Buenos Aires | Argentina | C1015ABO | ||
| 30 | Buenos Aires | Argentina | C1425DQK | ||
| 31 | Córdoba | Argentina | 5016 | ||
| 32 | San Isidro | Argentina | B1602BPPD | ||
| 33 | Tucuman | Argentina | T4000AXL | ||
| 34 | Adelaide | Australia | SA 5000 | ||
| 35 | Camperdown | Australia | 2050 | ||
| 36 | Melbourne | Australia | 3168 | ||
| 37 | Parkville | Australia | 3052 | ||
| 38 | Woodville | Australia | 5011 | ||
| 39 | Bruxelles | Belgium | 1200 | ||
| 40 | Leuven | Belgium | 3000 | ||
| 41 | Liege | Belgium | 4000 | ||
| 42 | Rio de Janeiro | Brazil | 20551-030 | ||
| 43 | Sao Paulo | Brazil | 04039-020 | ||
| 44 | Sorocaba | Brazil | 18030-210 | ||
| 45 | Vancouver | British Columbia | Canada | V5Z 1L7 | |
| 46 | Victoria | British Columbia | Canada | V8Z 7X8 | |
| 47 | Halifax | Nova Scotia | Canada | B3H 2Y9 | |
| 48 | London | Ontario | Canada | N6A 4V2 | |
| 49 | Toronto | Ontario | Canada | M5T 2S8 | |
| 50 | Montreal | Quebec | Canada | H1T 2M4 | |
| 51 | Beijing | China | 100034 | ||
| 52 | Guangdong | China | 510008 | ||
| 53 | Guangzhou | China | 510630 | ||
| 54 | Jiangsu | China | 210002 | ||
| 55 | Shanghai | China | 200001 | ||
| 56 | Brno | Czech Republic | 656 91 | ||
| 57 | Praha 2 | Czech Republic | 128 08 | ||
| 58 | Lille | France | 59037 | ||
| 59 | Lyon | France | 69437 | ||
| 60 | Nantes | France | 44035 | ||
| 61 | Paris | France | 75679 | ||
| 62 | Paris | France | 75877 | ||
| 63 | Toulouse | France | 31059 | ||
| 64 | Aachen | Germany | 52074 | ||
| 65 | Bad Bramstedt | Germany | 24576 | ||
| 66 | Berlin | Germany | 10117 | ||
| 67 | Berlin | Germany | 14059 | ||
| 68 | Dresden | Germany | 01307 | ||
| 69 | Düsseldorf | Germany | 40225 | ||
| 70 | Erlangen | Germany | 91054 | ||
| 71 | Hannover | Germany | 30625 | ||
| 72 | Leipzig | Germany | 04103 | ||
| 73 | Muenster | Germany | 48149 | ||
| 74 | München | Germany | 80336 | ||
| 75 | München | Germany | 81675 | ||
| 76 | Athens | Greece | 11521 | ||
| 77 | Athens | Greece | 11527 | ||
| 78 | Heraklion | Greece | 71500 | ||
| 79 | Debrecen | Hungary | 4032 | ||
| 80 | Pécs | Hungary | 7632 | ||
| 81 | Szeged | Hungary | 2724 | ||
| 82 | Brescia | Italy | 25125 | ||
| 83 | Milano | Italy | 20149 | ||
| 84 | Padova | Italy | 35128 | ||
| 85 | Pisa | Italy | 56100 | ||
| 86 | Udine | Italy | 33100 | ||
| 87 | Merida | Mexico | 97000 | ||
| 88 | Mexico City | Mexico | 14000 | ||
| 89 | San Luis Potosi | Mexico | 78240 | ||
| 90 | Lisboa | Portugal | |||
| 91 | Porto | Portugal | 4200-319 | ||
| 92 | Alicante | Spain | 03010 | ||
| 93 | Barcelona | Spain | 08035 | ||
| 94 | Barcelona | Spain | 08036 | ||
| 95 | Madrid | Spain | 28041 | ||
| 96 | Malaga | Spain | 29010 | ||
| 97 | Santander | Spain | 39008 | ||
| 98 | Sevilla | Spain | 41013 | ||
| 99 | Birmingham | United Kingdom | B15 2TT | ||
| 100 | Cambridge | United Kingdom | CB2 2QQ | ||
| 101 | Leeds | United Kingdom | LS1 3EX | ||
| 102 | London | United Kingdom | SE1 7EH | ||
| 103 | London | United Kingdom | W12 OHS | ||
| 104 | London | United Kingdom | WIT 4NJ | ||
| 105 | Manchester | United Kingdom | M13 9WL | ||
| 106 | Newcastle Upon Tyne | United Kingdom | NE7 7DN | ||
| 107 | Sheffield | United Kingdom | S10 2JF | ||
| 108 | Southampton | United Kingdom | SO16 6YD |
Sponsors and Collaborators
- Hoffmann-La Roche
- Aspreva Pharmaceuticals
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00377637
Other Study ID Numbers:
- WX17801
- NCT00121082
First Posted:
Sep 18, 2006
Last Update Posted:
Dec 6, 2011
Last Verified:
Oct 1, 2011
Additional relevant MeSH terms:
Study Results
Participant Flow
| 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 Detail |
| Arm/Group Title | Induction Phase: Cyclophosphamide | Induction Phase: Mycophenolate Mofetil | Maintenance Phase: Mycophenolate Mofetil | Maintenance Phase: Azathioprine |
|---|---|---|---|---|
| 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 | 185 | 0 | 0 |
| Safety Population | 180 | 184 | 0 | 0 |
| COMPLETED | 156 | 150 | 0 | 0 |
| NOT COMPLETED | 29 | 35 | 0 | 0 |
| Period Title: Induction Phase | ||||
| STARTED | 0 | 0 | 116 | 111 |
| COMPLETED | 0 | 0 | 73 | 54 |
| NOT COMPLETED | 0 | 0 | 43 | 57 |
Baseline Characteristics
| Arm/Group Title | Induction Phase: Cyclophosphamide | Induction Phase: Mycophenolate Mofetil | Maintenance Phase: Mycophenolate Mofetil | Maintenance Phase: Azathioprine | Total |
|---|---|---|---|---|---|
| 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 Participants | 185 | 185 | 116 | 111 | 597 |
| Age, Customized (years) [Mean (Standard Deviation) ] | |||||
| Induction Phase |
31.3
(10.25)
|
32.4
(11.7)
|
NA
(NA)
|
NA
(NA)
|
31.9
(10.72)
|
| Maintenance Phase |
NA
(NA)
|
NA
(NA)
|
31.8
(10.59)
|
31.0
(10.77)
|
31.4
(10.65)
|
| Sex/Gender, Customized (Number) [Number] | |||||
| Induction Phase - Female |
156
84.3%
|
157
84.9%
|
0
0%
|
0
0%
|
313
52.4%
|
| Induction Phase - Male |
29
15.7%
|
28
15.1%
|
0
0%
|
0
0%
|
57
9.5%
|
| Maintenance Phase - Female |
0
0%
|
0
0%
|
99
85.3%
|
96
86.5%
|
195
32.7%
|
| Maintenance Phase - Male |
0
0%
|
0
0%
|
17
14.7%
|
15
13.5%
|
32
5.4%
|
Outcome Measures
| Title | Induction Phase: Number of Patients Showing Treatment Response |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 185 | 185 |
| Responder |
98
53%
|
104
56.2%
|
| Non-responder |
87
47%
|
81
43.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Intravenous Cyclophosphamide, Mycophenolate Mofetil |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.478 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Covariates included Treatment, Race, Geographical Region, and WHO Lupus Nephritis Class V and specified interaction terms. | |
| Title | Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 116 | 111 |
| Start of Maintenance Phase to Month 3 |
98.2
53.1%
|
97.2
52.5%
|
| Month 3 to Month 6 |
93.7
50.6%
|
89.3
48.3%
|
| Month 6 to Month 9 |
89.9
48.6%
|
86.2
46.6%
|
| Month 9 to Month 12 |
86.0
46.5%
|
83.0
44.9%
|
| Month 12 to Month 15 |
86.0
46.5%
|
77.5
41.9%
|
| Month 15 to Month 18 |
84.9
45.9%
|
74.1
40.1%
|
| Month 18 to Month 21 |
84.9
45.9%
|
70.7
38.2%
|
| Month 21 to Month 24 |
83.9
45.4%
|
68.3
36.9%
|
| Month 24 to Month 27 |
82.8
44.8%
|
67.1
36.3%
|
| Month 27 to Month 30 |
82.8
44.8%
|
65.9
35.6%
|
| Month 30 to Month 33 |
81.7
44.2%
|
63.4
34.3%
|
| Month 33 to Month 36 |
81.7
44.2%
|
58.6
31.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Intravenous Cyclophosphamide, Mycophenolate Mofetil |
|---|---|---|
| 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 | ||
| 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 | ||
| Title | Induction Phase: Number of Participants Achieving Complete Remission |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was intent to treat. |
| Arm/Group Title | Intravenous Cyclophosphamide | Mycophenolate Mofetil |
|---|---|---|
| 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. |
| Measure Participants | 185 | 185 |
| Complete Remission - Yes |
15
8.1%
|
16
8.6%
|
| Complete Remission - No |
170
91.9%
|
169
91.4%
|
| Title | Induction Phase: Change From Baseline to Week 24 in Serum Creatinine |
|---|---|
| Description | |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 185 | 185 |
| 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)
|
| Title | Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein |
|---|---|
| Description | 24-hour urine protein was measured at Baseline and Week 24. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 185 | 185 |
| 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)
|
| Title | Induction Phase: Change From Baseline to Week 24 in Serum Albumin |
|---|---|
| Description | |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 185 | 185 |
| 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)
|
| Title | Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 181 | 181 |
| Shift from Baseline=A to 24 Week Endpoint=A |
27.1
14.6%
|
17.1
9.2%
|
| Shift from Baseline=A to 24 Week Endpoint=B |
34.8
18.8%
|
39.2
21.2%
|
| Shift from Baseline=A to 24 Week Endpoint=C |
24.9
13.5%
|
33.1
17.9%
|
| Shift from Baseline=A to 24 Week Endpoint=D |
9.4
5.1%
|
5.5
3%
|
| Shift from Baseline=B to 24 Week Endpoint=A |
0.0
0%
|
0.0
0%
|
| Shift from Baseline=B to 24 Week Endpoint=B |
1.1
0.6%
|
1.7
0.9%
|
| Shift from Baseline=B to 24 Week Endpoint=C |
1.7
0.9%
|
2.2
1.2%
|
| Shift from Baseline=B to 24 Week Endpoint=D |
0.0
0%
|
1.1
0.6%
|
| Shift from Baseline=C to 24 Week Endpoint=A |
0.0
0%
|
0.0
0%
|
| Shift from Baseline=C to 24 Week Endpoint=B |
0.6
0.3%
|
0.0
0%
|
| Shift from Baseline=C to 24 Week Endpoint=C |
0.0
0%
|
0.0
0%
|
| Shift from Baseline=C to 24 Week Endpoint=D |
0.0
0%
|
0.0
0%
|
| Shift from Baseline=D to 24 Week Endpoint=A |
0.0
0%
|
0.0
0%
|
| Shift from Baseline=D to 24 Week Endpoint=B |
0.0
0%
|
0.0
0%
|
| Shift from Baseline=D to 24 Week Endpoint=C |
0.6
0.3%
|
0.0
0%
|
| Shift from Baseline=D to 24 Week Endpoint=D |
0.0
0%
|
0.0
0%
|
| Title | Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 185 | 185 |
| 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)
|
| Title | Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Deaths |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Maintenance Phase intent to treat population. |
| Arm/Group Title | Mycophenolate Mofetil (MMF) | Azathioprine (AZA) |
|---|---|---|
| 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. |
| Measure Participants | 116 | 111 |
| Number [Deaths] |
0
|
1
|
| Title | Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With End-stage Renal Disease (ESRD) |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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 |
| Measure Participants | 116 | 111 |
| Number [participants] |
0
0%
|
3
1.6%
|
| Title | Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With Sustained Doubling of Serum Creatinine |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 116 | 111 |
| Number [participants] |
1
0.5%
|
5
2.7%
|
| Title | Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 116 | 111 |
| Start of Maintenance Phase to Month 3 |
98.2
53.1%
|
97.2
52.5%
|
| Month 3 to Month 6 |
94.6
51.1%
|
90.3
48.8%
|
| Month 6 to Month 9 |
90.8
49.1%
|
87.2
47.1%
|
| Month 9 to Month 12 |
87.8
47.5%
|
85.0
45.9%
|
| Month 12 to Month 15 |
87.8
47.5%
|
82.8
44.8%
|
| Month 15 to Month 18 |
86.8
46.9%
|
79.2
42.8%
|
| Month 18 to Month 21 |
86.8
46.9%
|
78.0
42.2%
|
| Month 21 to Month 24 |
86.8
46.9%
|
75.5
40.8%
|
| Month 24 to Month 27 |
86.8
46.9%
|
74.2
40.1%
|
| Month 27 to Month 30 |
86.8
46.9%
|
74.2
40.1%
|
| Month 30 to Month 33 |
85.6
46.3%
|
72.9
39.4%
|
| Month 33 to Month 36 |
85.6
46.3%
|
70.1
37.9%
|
| Title | Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 116 | 111 |
| Start of Maintenance Phase to Month 3 |
100
54.1%
|
99.1
53.6%
|
| Month 3 to Month 6 |
98.2
53.1%
|
95.1
51.4%
|
| Month 6 to Month 9 |
97.2
52.5%
|
93.0
50.3%
|
| Month 9 to Month 12 |
94.2
50.9%
|
91.9
49.7%
|
| Month 12 to Month 15 |
94.2
50.9%
|
88.4
47.8%
|
| Month 15 to Month 18 |
94.2
50.9%
|
87.1
47.1%
|
| Month 18 to Month 21 |
93.1
50.3%
|
83.1
44.9%
|
| Month 21 to Month 24 |
91.9
49.7%
|
83.1
44.9%
|
| Month 24 to Month 27 |
90.8
49.1%
|
81.7
44.2%
|
| Month 27 to Month 30 |
90.8
49.1%
|
80.3
43.4%
|
| Month 30 to Month 33 |
90.8
49.1%
|
78.8
42.6%
|
| Month 33 to Month 36 |
90.8
49.1%
|
75.9
41%
|
| Title | Maintenance Phase: Participants With Major Extra-renal Flare |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Maintenance Phase intent to treat population. |
| Arm/Group Title | Mycophenolate Mofetil | Azathioprine |
|---|---|---|
| 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. |
| Measure Participants | 116 | 111 |
| Number [participants] |
7
3.8%
|
6
3.2%
|
Adverse Events
| 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 | ||||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Induction Phase: Cyclophosphamide | Induction Phase: Mycophenolate Mofetil | Maintenance Phase: Mycophenolate Mofetil | Maintenance Phase: Azathioprine | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 41/180 (22.8%) | 51/184 (27.7%) | 27/115 (23.5%) | 37/111 (33.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/180 (0.6%) | 2/184 (1.1%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Leukopenia | 2/180 (1.1%) | 1/184 (0.5%) | 0/115 (0%) | 4/111 (3.6%) | ||||
| Neutropenia | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Thrombotic thrombocytopenic purpura | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Thrombocytopenia | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Febrile neutropenia | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Cardiac disorders | ||||||||
| Acute coronary syndrome | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Myocardial infarction | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Cardiac arrest | 1/180 (0.6%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Pericardial effusion | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Acute myocardial infarction | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Pericarditis | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Deafness neurosensory | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 0/180 (0%) | 3/184 (1.6%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Vomiting | 1/180 (0.6%) | 2/184 (1.1%) | 0/115 (0%) | 0/111 (0%) | ||||
| Dyspepsia | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Abdominal pain | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Gastrooesophageal reflux disease | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Abdominal distension | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Gingivitis | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Pancreatitis | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Gastritis | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| General disorders | ||||||||
| Death | 1/180 (0.6%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Pyrexia | 3/180 (1.7%) | 1/184 (0.5%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Oedema | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Non-cardiac chest pain | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 1/111 (0.9%) | ||||
| Chest pain | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatic function abnormal | 1/180 (0.6%) | 0/184 (0%) | 1/115 (0.9%) | 1/111 (0.9%) | ||||
| Cholecystitis acute | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 1/111 (0.9%) | ||||
| Immune system disorders | ||||||||
| Anaphylactic reaction | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Infections and infestations | ||||||||
| Pneumonia | 3/180 (1.7%) | 5/184 (2.7%) | 2/115 (1.7%) | 1/111 (0.9%) | ||||
| Bronchitis | 1/180 (0.6%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Bronchopneumonia | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Lung infection | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Lobar pneumonia | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Herpes zoster | 2/180 (1.1%) | 5/184 (2.7%) | 1/115 (0.9%) | 1/111 (0.9%) | ||||
| Herpes simplex | 1/180 (0.6%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Septic shock | 0/180 (0%) | 2/184 (1.1%) | 0/115 (0%) | 0/111 (0%) | ||||
| Acinetobacter bacteraemia | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Meningitis tuberculous | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Pulmonary tuberculosis | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Tuberculosis gastrointestinal | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Gastroenteritis | 0/180 (0%) | 1/184 (0.5%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Retroperitoneal abscess | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Gastrointestinal infection | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Skin infection | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Subcutaneous abscess | 0/180 (0%) | 1/184 (0.5%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Fungaemia | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Respiratory tract infection | 2/180 (1.1%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Infection | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Meningitis streptococcal | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Viral infection | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Gastroenteritis viral | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Cellulitis | 2/180 (1.1%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Meningitis bacterial | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Subacute endocarditis | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Tonsillitis | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Upper respiratory tract infection | 4/180 (2.2%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Osteomyelitis | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Wound infection | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Influenza | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Urosepsis | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Disseminated tuberculosis | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Pyelonephritis | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Appendicitis | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 2/111 (1.8%) | ||||
| Peridiverticulitis | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Sepsis | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Cystitis | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Genitourinary tract infection | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Pneumonia bacterial | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Tubo-ovarian abscess | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Viral upper respiratory tract infection | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Overdose | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Head injury | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Hip fracture | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Foot fracture | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Road traffic accident | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Traumatic hematoma | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Wrist fracture | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Investigations | ||||||||
| Platelet count decreased | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| White blood cell count decreased | 1/180 (0.6%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| International normalised ratio increased | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Alanine aminotransferase increased | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Blood creatinine increased | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Biopsy kidney | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypokalaemia | 0/180 (0%) | 2/184 (1.1%) | 0/115 (0%) | 0/111 (0%) | ||||
| Hyperkalaemia | 1/180 (0.6%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Diabetes mellitus | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Dehydration | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Fluid overload | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Hypoalbuminaemia | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Systemic lupus erythematosus | 4/180 (2.2%) | 2/184 (1.1%) | 3/115 (2.6%) | 2/111 (1.8%) | ||||
| Arthralgia | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Pain in extremity | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Costochondritis | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Myositis | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Osteonecrosis | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Rhabdomyolysis | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Ovarian germ cell teratoma benign | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Uterine leiomyoma | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Uterine carcinoma in situ | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Nervous system disorders | ||||||||
| Headache | 0/180 (0%) | 1/184 (0.5%) | 1/115 (0.9%) | 1/111 (0.9%) | ||||
| Brain oedema | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Cerebrovascular accident | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Syncope | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Lupus encephalitis | 2/180 (1.1%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Convulsion | 3/180 (1.7%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Cerebral infarction | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Tremor | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Superior sagittal sinus thrombosis | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Pregnancy, puerperium and perinatal conditions | ||||||||
| Pregnancy | 0/180 (0%) | 2/184 (1.1%) | 3/115 (2.6%) | 6/111 (5.4%) | ||||
| Pre-eclampsia | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 1/111 (0.9%) | ||||
| Premature baby | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Psychiatric disorders | ||||||||
| Depression | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Psychotic disorder | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Abnormal behavior | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Major depression | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Panic attack | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Suicidal ideation | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Renal and urinary disorders | ||||||||
| Renal failure acute | 0/180 (0%) | 3/184 (1.6%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Renal failure | 1/180 (0.6%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Renal impairment | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Renal failure chronic | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Lupus nephritis | 0/180 (0%) | 2/184 (1.1%) | 1/115 (0.9%) | 5/111 (4.5%) | ||||
| Proteinuria | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Nephrotic syndrome | 2/180 (1.1%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Hematuria | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Renal colic | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Uterine haemorrhage | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Cervical dysplasia | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Menometrorrhagia | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Ovarian hemorrhage | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Haemoptysis | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Pulmonary haemorrhage | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Interstitial lung disease | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Pulmonary embolism | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Respiratory failure | 0/180 (0%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Lupus pneumonitis | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Pharyngolaryngeal pain | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Pulmonary hypertension | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis exfoliative | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Panniculitis | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Rash maculo-papular | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Angioedema | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Surgical and medical procedures | ||||||||
| Abortion induced | 0/180 (0%) | 0/184 (0%) | 2/115 (1.7%) | 4/111 (3.6%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 1/180 (0.6%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Hypertension | 1/180 (0.6%) | 1/184 (0.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Venous stenosis | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Subclavian vein thrombosis | 1/180 (0.6%) | 0/184 (0%) | 0/115 (0%) | 0/111 (0%) | ||||
| Peripheral ischemia | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 0/111 (0%) | ||||
| Thrombosis | 0/180 (0%) | 0/184 (0%) | 0/115 (0%) | 1/111 (0.9%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Induction Phase: Cyclophosphamide | Induction Phase: Mycophenolate Mofetil | Maintenance Phase: Mycophenolate Mofetil | Maintenance Phase: Azathioprine | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 171/180 (95%) | 177/184 (96.2%) | 113/115 (98.3%) | 108/111 (97.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 12/180 (6.7%) | 23/184 (12.5%) | 13/115 (11.3%) | 17/111 (15.3%) | ||||
| Leukopenia | 38/180 (21.1%) | 11/184 (6%) | 26/115 (22.6%) | 40/111 (36%) | ||||
| Neutropenia | 12/180 (6.7%) | 3/184 (1.6%) | 0/115 (0%) | 0/111 (0%) | ||||
| Cardiac disorders | ||||||||
| Palpitations | 6/180 (3.3%) | 11/184 (6%) | 0/115 (0%) | 0/111 (0%) | ||||
| Tachycardia | 6/180 (3.3%) | 10/184 (5.4%) | 0/115 (0%) | 0/111 (0%) | ||||
| Endocrine disorders | ||||||||
| Cushingoid | 11/180 (6.1%) | 9/184 (4.9%) | 0/115 (0%) | 0/111 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 23/180 (12.8%) | 52/184 (28.3%) | 22/115 (19.1%) | 20/111 (18%) | ||||
| Nausea | 82/180 (45.6%) | 27/184 (14.7%) | 20/115 (17.4%) | 21/111 (18.9%) | ||||
| Vomiting | 68/180 (37.8%) | 25/184 (13.6%) | 14/115 (12.2%) | 18/111 (16.2%) | ||||
| Abdominal pain | 13/180 (7.2%) | 19/184 (10.3%) | 11/115 (9.6%) | 14/111 (12.6%) | ||||
| Abdominal pain upper | 18/180 (10%) | 15/184 (8.2%) | 13/115 (11.3%) | 11/111 (9.9%) | ||||
| Constipation | 9/180 (5%) | 12/184 (6.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Dyspepsia | 5/180 (2.8%) | 10/184 (5.4%) | 3/115 (2.6%) | 7/111 (6.3%) | ||||
| Gastritis | 0/180 (0%) | 0/184 (0%) | 11/115 (9.6%) | 7/111 (6.3%) | ||||
| Mouth ulceration | 0/180 (0%) | 0/184 (0%) | 8/115 (7%) | 4/111 (3.6%) | ||||
| Toothache | 0/180 (0%) | 0/184 (0%) | 5/115 (4.3%) | 9/111 (8.1%) | ||||
| General disorders | ||||||||
| Oedema peripheral | 30/180 (16.7%) | 35/184 (19%) | 8/115 (7%) | 7/111 (6.3%) | ||||
| Oedema | 17/180 (9.4%) | 11/184 (6%) | 0/115 (0%) | 0/111 (0%) | ||||
| Fatigue | 18/180 (10%) | 18/184 (9.8%) | 17/115 (14.8%) | 20/111 (18%) | ||||
| Asthenia | 15/180 (8.3%) | 9/184 (4.9%) | 6/115 (5.2%) | 6/111 (5.4%) | ||||
| Chest pain | 10/180 (5.6%) | 8/184 (4.3%) | 0/115 (0%) | 0/111 (0%) | ||||
| Pyrexia | 30/180 (16.7%) | 12/184 (6.5%) | 0/115 (0%) | 0/111 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatic function abnormal | 0/180 (0%) | 0/184 (0%) | 4/115 (3.5%) | 6/111 (5.4%) | ||||
| Infections and infestations | ||||||||
| Nasopharyngitis | 29/180 (16.1%) | 25/184 (13.6%) | 15/115 (13%) | 13/111 (11.7%) | ||||
| Upper respiratory tract infection | 28/180 (15.6%) | 17/184 (9.2%) | 41/115 (35.7%) | 36/111 (32.4%) | ||||
| Herpes zoster | 6/180 (3.3%) | 14/184 (7.6%) | 7/115 (6.1%) | 6/111 (5.4%) | ||||
| Urinary tract infection | 17/180 (9.4%) | 19/184 (10.3%) | 20/115 (17.4%) | 27/111 (24.3%) | ||||
| Sinusitis | 0/180 (0%) | 0/184 (0%) | 10/115 (8.7%) | 4/111 (3.6%) | ||||
| Pharyngitis | 0/180 (0%) | 0/184 (0%) | 6/115 (5.2%) | 6/111 (5.4%) | ||||
| Bronchitis | 0/180 (0%) | 0/184 (0%) | 14/115 (12.2%) | 7/111 (6.3%) | ||||
| Gastroenteritis | 0/180 (0%) | 0/184 (0%) | 16/115 (13.9%) | 6/111 (5.4%) | ||||
| Influenza | 0/180 (0%) | 0/184 (0%) | 13/115 (11.3%) | 14/111 (12.6%) | ||||
| Respiratory tract infection | 0/180 (0%) | 0/184 (0%) | 7/115 (6.1%) | 3/111 (2.7%) | ||||
| Investigations | ||||||||
| White blood cell count decreased | 16/180 (8.9%) | 5/184 (2.7%) | 0/115 (0%) | 0/111 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypokalaemia | 3/180 (1.7%) | 13/184 (7.1%) | 6/115 (5.2%) | 1/111 (0.9%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 43/180 (23.9%) | 29/184 (15.8%) | 29/115 (25.2%) | 32/111 (28.8%) | ||||
| Back pain | 16/180 (8.9%) | 19/184 (10.3%) | 13/115 (11.3%) | 13/111 (11.7%) | ||||
| Pain in extremity | 9/180 (5%) | 6/184 (3.3%) | 10/115 (8.7%) | 9/111 (8.1%) | ||||
| Arthritis | 10/180 (5.6%) | 4/184 (2.2%) | 8/115 (7%) | 11/111 (9.9%) | ||||
| Musculoskeletal pain | 0/180 (0%) | 0/184 (0%) | 6/115 (5.2%) | 1/111 (0.9%) | ||||
| Myalgia | 0/180 (0%) | 0/184 (0%) | 7/115 (6.1%) | 5/111 (4.5%) | ||||
| Systemic lupus erythematosus | 0/180 (0%) | 0/184 (0%) | 6/115 (5.2%) | 15/111 (13.5%) | ||||
| Muscle spasms | 0/180 (0%) | 0/184 (0%) | 1/115 (0.9%) | 6/111 (5.4%) | ||||
| Nervous system disorders | ||||||||
| Headache | 47/180 (26.1%) | 38/184 (20.7%) | 25/115 (21.7%) | 27/111 (24.3%) | ||||
| Dizziness | 10/180 (5.6%) | 8/184 (4.3%) | 5/115 (4.3%) | 10/111 (9%) | ||||
| Pregnancy, puerperium and perinatal conditions | ||||||||
| Pregnancy | 0/180 (0%) | 0/184 (0%) | 3/115 (2.6%) | 6/111 (5.4%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 11/180 (6.1%) | 10/184 (5.4%) | 11/115 (9.6%) | 3/111 (2.7%) | ||||
| Renal and urinary disorders | ||||||||
| Lupus nephritis | 0/180 (0%) | 0/184 (0%) | 17/115 (14.8%) | 25/111 (22.5%) | ||||
| Proteinuria | 0/180 (0%) | 0/184 (0%) | 11/115 (9.6%) | 4/111 (3.6%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 16/180 (8.9%) | 24/184 (13%) | 16/115 (13.9%) | 14/111 (12.6%) | ||||
| Dyspnoea | 6/180 (3.3%) | 10/184 (5.4%) | 4/115 (3.5%) | 6/111 (5.4%) | ||||
| Oropharyngeal pain | 0/180 (0%) | 0/184 (0%) | 5/115 (4.3%) | 7/111 (6.3%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 64/180 (35.6%) | 20/184 (10.9%) | 12/115 (10.4%) | 11/111 (9.9%) | ||||
| Rash | 21/180 (11.7%) | 19/184 (10.3%) | 15/115 (13%) | 14/111 (12.6%) | ||||
| Acne | 9/180 (5%) | 9/184 (4.9%) | 0/115 (0%) | 0/111 (0%) | ||||
| Erythema | 10/180 (5.6%) | 5/184 (2.7%) | 0/115 (0%) | 0/111 (0%) | ||||
| Butterfly rash | 0/180 (0%) | 0/184 (0%) | 7/115 (6.1%) | 11/111 (9.9%) | ||||
| Skin lesion | 0/180 (0%) | 0/184 (0%) | 6/115 (5.2%) | 4/111 (3.6%) | ||||
| Pruritus | 0/180 (0%) | 0/184 (0%) | 2/115 (1.7%) | 8/111 (7.2%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 25/180 (13.9%) | 26/184 (14.1%) | 8/115 (7%) | 7/111 (6.3%) | ||||
| Raynaud's phenomenon | 0/180 (0%) | 0/184 (0%) | 3/115 (2.6%) | 9/111 (8.1%) | ||||
Limitations/Caveats
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.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffman-LaRoche |
| Phone | 800-821-8590 |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00377637
Other Study ID Numbers:
- WX17801
- NCT00121082
First Posted:
Sep 18, 2006
Last Update Posted:
Dec 6, 2011
Last Verified:
Oct 1, 2011