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Enteric-coated Mycophenolate Sodium (EC-MPS) With Reduced-dose Tacrolimus Versus EC-MPS With Standard-dose Tacrolimus in Stable Kidney Transplant Recipients (OLYMPE)

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ClinicalTrials.gov Identifier: NCT00284934
Recruitment Status : Completed
First Posted : February 1, 2006
Results First Posted : May 2, 2011
Last Update Posted : May 2, 2011
Sponsor:
Information provided by:
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Kidney Diseases
Interventions Drug: Enteric-coated mycophenolate sodium (EC-MPS)
Drug: Tacrolimus
Drug: Corticosteroids
Enrollment 94
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Standard Dose EC-MPS High EC-MPS
Hide Arm/Group Description Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day. Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Period Title: Overall Study
Started 48 46
Intent-to-treat Population (ITT) 47 45
Completed 44 43
Not Completed 4 3
Reason Not Completed
Adverse Event             1             2
Other reasons             3             1
Arm/Group Title Standard Dose EC-MPS High EC-MPS Total
Hide Arm/Group Description Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day. Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day. Total of all reporting groups
Overall Number of Baseline Participants 47 45 92
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 47 participants 45 participants 92 participants
54.5  (10.4) 50.7  (12.2) 52.7  (11)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 47 participants 45 participants 92 participants
< 45 11 13 24
45-60 18 20 38
>= 60 18 12 30
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants 45 participants 92 participants
Female
16
  34.0%
15
  33.3%
31
  33.7%
Male
31
  66.0%
30
  66.7%
61
  66.3%
1.Primary Outcome
Title Renal Function Assessed by Change in Estimated Glomerular Filtration Rate(eGFR)
Hide Description Change in estimated glomerular filtration rate from baseline to Month 6 calculated by using abbreviated Modification of Diet in Renal Disease (MDRD) formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where -C is the serum concentration of creatinine [mg/dL], -A is patient age at sample collection date [years], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1.
Time Frame Baseline and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population was defined as all patients who were randomized and treated with study medication and had at least one post-treatment efficacy assessment.
Arm/Group Title Standard Dose EC-MPS High EC-MPS
Hide Arm/Group Description:
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Overall Number of Participants Analyzed 47 45
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
Baseline (n= 47, 45) 45.3  (9.5) 56.4  (11.2)
Month 6 (n= 45, 43) 44.7  (11.5) 49.1  (11.11)
Change from Baseline - Month 6 (n= 45, 43) -0.4  (6.9) 2.4  (6.1)
2.Secondary Outcome
Title Renal Function at 3 Months Assessed by Change in Estimated Glomerular Filtration Rate (eGFR)
Hide Description Change in estimated glomerular filtration rate from baseline to Month 3 calculated by using abbreviated MDRD formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where -C is the serum concentration of creatinine [mg/dL], -A is patient age at sample collection date [years], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1.
Time Frame Baseline and 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population was defined as all patients who were randomized and treated with study medication and had at least one post-treatment efficacy assessment.
Arm/Group Title Standard Dose EC-MPS High EC-MPS
Hide Arm/Group Description:
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Overall Number of Participants Analyzed 47 45
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
Baseline (n= 47, 45) 45.3  (9.5) 46.4  (11.2)
Month 3 (n= 44, 43) 44.6  (10.9) 48.6  (10.8)
Change from Baseline to Month 3 (n= 44, 43) -0.4  (4.6) 2.1  (4.9)
3.Secondary Outcome
Title Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months
Hide Description A biopsy-proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB, or III based on the Banff 1997 classification.The allograft was presumed lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient went through a graft nephrectomy, then the day of nephrectomy was the day of graft loss.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population was defined as all patients who were randomized and treated with study medication and had at least one post-treatment efficacy assessment.
Arm/Group Title Standard Dose EC-MPS High EC-MPS
Hide Arm/Group Description:
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Overall Number of Participants Analyzed 47 45
Measure Type: Number
Unit of Measure: Participants
Biopsy proven acute rejection 0 0
Treated acute rejection 0 0
Graft loss 0 0
Death 0 0
4.Secondary Outcome
Title Number of Participants With Graft and Patient Survivals at 6 Months
Hide Description Graft survival was defined as the number of patients with no graft loss. The allograft was presumed lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient went through a graft nephrectomy, then the day of nephrectomy was the day of graft loss. Patient survival was defined as the number of patients alive with or without a functioning graft.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population was defined as all patients who were randomized and treated with study medication and had at least one post-treatment efficacy assessment.
Arm/Group Title Standard Dose EC-MPS High EC-MPS
Hide Arm/Group Description:
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Overall Number of Participants Analyzed 47 45
Measure Type: Number
Unit of Measure: Participants
Graft survival 47 45
Patient survival 47 45
Time Frame 6 months
Adverse Event Reporting Description Safety population
 
Arm/Group Title Standard Dose EC-MPS High EC-MPS
Hide Arm/Group Description Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day. Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
All-Cause Mortality
Standard Dose EC-MPS High EC-MPS
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Standard Dose EC-MPS High EC-MPS
Affected / at Risk (%) Affected / at Risk (%)
Total   8/47 (17.02%)   7/45 (15.56%) 
Blood and lymphatic system disorders     
Neutropenia † 1  0/47 (0.00%)  1/45 (2.22%) 
Cardiac disorders     
Acute coronary syndrome † 1  1/47 (2.13%)  0/45 (0.00%) 
Arrhythmia † 1  0/47 (0.00%)  1/45 (2.22%) 
Cardiac disorder † 1  0/47 (0.00%)  1/45 (2.22%) 
Ischaemic cardiomyopathy † 1  0/47 (0.00%)  1/45 (2.22%) 
Gastrointestinal disorders     
Colonic polyp † 1  0/47 (0.00%)  1/45 (2.22%) 
Diarrhoea † 1  1/47 (2.13%)  1/45 (2.22%) 
General disorders     
Pyrexia † 1  0/47 (0.00%)  1/45 (2.22%) 
Infections and infestations     
Bronchitis † 1  0/47 (0.00%)  1/45 (2.22%) 
Bursitis infective † 1  1/47 (2.13%)  0/45 (0.00%) 
Gastroenteritis † 1  2/47 (4.26%)  0/45 (0.00%) 
Pneumocystis jiroveci infection † 1  0/47 (0.00%)  1/45 (2.22%) 
Pyelonephritis † 1  1/47 (2.13%)  0/45 (0.00%) 
Injury, poisoning and procedural complications     
Arteriovenous fistula thrombosis † 1  1/47 (2.13%)  0/45 (0.00%) 
Investigations     
Blood creatinine increased † 1  0/47 (0.00%)  1/45 (2.22%) 
Metabolism and nutrition disorders     
Hypoglycaemia † 1  0/47 (0.00%)  1/45 (2.22%) 
Nervous system disorders     
Convulsion † 1  0/47 (0.00%)  1/45 (2.22%) 
Presyncope † 1  1/47 (2.13%)  0/45 (0.00%) 
Renal and urinary disorders     
Renal failure † 1  1/47 (2.13%)  0/45 (0.00%) 
Renal impairment † 1  0/47 (0.00%)  1/45 (2.22%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease † 1  1/47 (2.13%)  0/45 (0.00%) 
Surgical and medical procedures     
Aortic valve replacement † 1  0/47 (0.00%)  1/45 (2.22%) 
Coronary angioplasty † 1  1/47 (2.13%)  0/45 (0.00%) 
Vascular disorders     
Femoral artery aneurysm † 1  1/47 (2.13%)  0/45 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Standard Dose EC-MPS High EC-MPS
Affected / at Risk (%) Affected / at Risk (%)
Total   4/47 (8.51%)   10/45 (22.22%) 
Blood and lymphatic system disorders     
Anaemia † 1  0/47 (0.00%)  3/45 (6.67%) 
Gastrointestinal disorders     
Diarrhoea † 1  4/47 (8.51%)  6/45 (13.33%) 
Metabolism and nutrition disorders     
Dyslipidaemia † 1  0/47 (0.00%)  4/45 (8.89%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[Not Specified]
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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00284934    
Other Study ID Numbers: CERL080AFR04
First Submitted: January 30, 2006
First Posted: February 1, 2006
Results First Submitted: December 20, 2010
Results First Posted: May 2, 2011
Last Update Posted: May 2, 2011