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Efficacy and Safety of Everolimus With Enteric-Coated Mycophenolate Sodium (EC-MPS) in a Cyclosporine Microemulsion-free Regimen Compared to Standard Therapy in de Novo Renal Transplant Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00154310
First received: September 8, 2005
Last updated: October 21, 2013
Last verified: October 2013
Results First Received: January 11, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Renal Transplantation
Interventions: Drug: Everolimus
Drug: Cyclosporine
Drug: Enteric-coated mycophenolate sodium
Drug: Corticosteroids

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was an open-label, randomized, parallel-group, multi-center study with two treatment groups, cyclosporine continuation and cyclosporine withdrawal starting from Month 4.5 post-transplant. Study started in June 2005 and ended in September 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Everolimus + Mycophenolate Sodium Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.
Cyclosporine + Mycophenolate Sodium Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.

Participant Flow:   Overall Study
    Everolimus + Mycophenolate Sodium   Cyclosporine + Mycophenolate Sodium
STARTED   155 [1]   145 
COMPLETED   118   117 
NOT COMPLETED   37   28 
Adverse Event                19                9 
Lack of Efficacy                5                4 
Protocol Violation                4                2 
Withdrawal by Subject                9                3 
Lost to Follow-up                0                8 
Administrative problems                0                1 
Death                0                1 
[1] "Started" indicates enrolled participants. Randomized participants for two arms are 154 and 146.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Everolimus + Mycophenolate Sodium Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.
Cyclosporine + Mycophenolate Sodium Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
Total Total of all reporting groups

Baseline Measures
   Everolimus + Mycophenolate Sodium   Cyclosporine + Mycophenolate Sodium   Total 
Overall Participants Analyzed 
[Units: Participants]
 155   145   300 
Age 
[Units: Years]
Mean (Standard Deviation)
 46.9  (11.67)   46.7  (11.85)   46.8  (11.73) 
Gender 
[Units: Participants]
     
Female   53   59   112 
Male   102   86   188 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Renal Function (Nankivell Formula) at Month 12 Post Transplantation.   [ Time Frame: at Month 12 post transplantation ]

2.  Secondary:   Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death   [ Time Frame: Up to Month 12 ]

3.  Secondary:   Number of Participants With Occurrence of Treatment Failures   [ Time Frame: up to or at Month 12 ]

4.  Secondary:   Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12   [ Time Frame: Month 4.5 and Month 12 ]

5.  Secondary:   Number of Participants Who Experienced an Adverse Event or Serious Adverse Event   [ Time Frame: Aes from end of core study period (month 12) to end of follow-up period (month 60) ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Certican Certican
Sandimmun Optoral Sandimmun Optoral

Other Adverse Events
    Certican   Sandimmun Optoral
Total, other (not including serious) adverse events     
# participants affected / at risk   155/155 (100.00%)   145/145 (100.00%) 
Blood and lymphatic system disorders     
Anaemia † 1     
# participants affected / at risk   43/155 (27.74%)   35/145 (24.14%) 
Leukocytosis † 1     
# participants affected / at risk   17/155 (10.97%)   22/145 (15.17%) 
Leukopenia † 1     
# participants affected / at risk   24/155 (15.48%)   24/145 (16.55%) 
Thrombocytopenia † 1     
# participants affected / at risk   18/155 (11.61%)   5/145 (3.45%) 
Ear and labyrinth disorders     
Vertigo † 1     
# participants affected / at risk   7/155 (4.52%)   9/145 (6.21%) 
Gastrointestinal disorders     
Abdominal pain † 1     
# participants affected / at risk   20/155 (12.90%)   14/145 (9.66%) 
Abdominal pain upper † 1     
# participants affected / at risk   12/155 (7.74%)   12/145 (8.28%) 
Aphthous stomatitis † 1     
# participants affected / at risk   22/155 (14.19%)   3/145 (2.07%) 
Constipation † 1     
# participants affected / at risk   82/155 (52.90%)   72/145 (49.66%) 
Diarrhoea † 1     
# participants affected / at risk   60/155 (38.71%)   42/145 (28.97%) 
Dyspepsia † 1     
# participants affected / at risk   15/155 (9.68%)   11/145 (7.59%) 
Flatulence † 1     
# participants affected / at risk   25/155 (16.13%)   20/145 (13.79%) 
Nausea † 1     
# participants affected / at risk   64/155 (41.29%)   59/145 (40.69%) 
Vomiting † 1     
# participants affected / at risk   38/155 (24.52%)   32/145 (22.07%) 
General disorders     
Asthenia † 1     
# participants affected / at risk   2/155 (1.29%)   9/145 (6.21%) 
Fatigue † 1     
# participants affected / at risk   7/155 (4.52%)   10/145 (6.90%) 
Impaired healing † 1     
# participants affected / at risk   8/155 (5.16%)   5/145 (3.45%) 
Oedema † 1     
# participants affected / at risk   44/155 (28.39%)   34/145 (23.45%) 
Oedema peripheral † 1     
# participants affected / at risk   38/155 (24.52%)   32/145 (22.07%) 
Pain † 1     
# participants affected / at risk   30/155 (19.35%)   26/145 (17.93%) 
Pyrexia † 1     
# participants affected / at risk   24/155 (15.48%)   22/145 (15.17%) 
Infections and infestations     
Bronchitis † 1     
# participants affected / at risk   16/155 (10.32%)   7/145 (4.83%) 
Cytomegalovirus infection † 1     
# participants affected / at risk   26/155 (16.77%)   24/145 (16.55%) 
Gastroenteritis † 1     
# participants affected / at risk   15/155 (9.68%)   17/145 (11.72%) 
Gastrointestinal infection † 1     
# participants affected / at risk   10/155 (6.45%)   7/145 (4.83%) 
Herpes zoster † 1     
# participants affected / at risk   8/155 (5.16%)   10/145 (6.90%) 
Human polyomavirus infection † 1     
# participants affected / at risk   8/155 (5.16%)   3/145 (2.07%) 
Infection † 1     
# participants affected / at risk   9/155 (5.81%)   9/145 (6.21%) 
Nasopharyngitis † 1     
# participants affected / at risk   49/155 (31.61%)   44/145 (30.34%) 
Oral herpes † 1     
# participants affected / at risk   11/155 (7.10%)   1/145 (0.69%) 
Pneumonia † 1     
# participants affected / at risk   16/155 (10.32%)   9/145 (6.21%) 
Respiratory tract infection † 1     
# participants affected / at risk   12/155 (7.74%)   12/145 (8.28%) 
Rhinitis † 1     
# participants affected / at risk   12/155 (7.74%)   8/145 (5.52%) 
Upper respiratory tract infection † 1     
# participants affected / at risk   12/155 (7.74%)   7/145 (4.83%) 
Urinary tract infection † 1     
# participants affected / at risk   90/155 (58.06%)   83/145 (57.24%) 
Wound infection † 1     
# participants affected / at risk   4/155 (2.58%)   11/145 (7.59%) 
Injury, poisoning and procedural complications     
Complications of transplanted kidney † 1     
# participants affected / at risk   21/155 (13.55%)   24/145 (16.55%) 
Procedural pain † 1     
# participants affected / at risk   50/155 (32.26%)   48/145 (33.10%) 
Wound complication † 1     
# participants affected / at risk   51/155 (32.90%)   46/145 (31.72%) 
Wound dehiscence † 1     
# participants affected / at risk   6/155 (3.87%)   8/145 (5.52%) 
Investigations     
Blood creatinine increased † 1     
# participants affected / at risk   51/155 (32.90%)   49/145 (33.79%) 
C-reactive protein increased † 1     
# participants affected / at risk   7/155 (4.52%)   8/145 (5.52%) 
Weight increased † 1     
# participants affected / at risk   8/155 (5.16%)   14/145 (9.66%) 
Metabolism and nutrition disorders     
Diabetes mellitus † 1     
# participants affected / at risk   19/155 (12.26%)   12/145 (8.28%) 
Fluid retention † 1     
# participants affected / at risk   6/155 (3.87%)   12/145 (8.28%) 
Hypercalcaemia † 1     
# participants affected / at risk   15/155 (9.68%)   25/145 (17.24%) 
Hypercholesterolaemia † 1     
# participants affected / at risk   45/155 (29.03%)   41/145 (28.28%) 
Hyperglycaemia † 1     
# participants affected / at risk   24/155 (15.48%)   16/145 (11.03%) 
Hyperkalaemia † 1     
# participants affected / at risk   18/155 (11.61%)   21/145 (14.48%) 
Hyperlipidaemia † 1     
# participants affected / at risk   23/155 (14.84%)   16/145 (11.03%) 
Hyperphosphataemia † 1     
# participants affected / at risk   11/155 (7.10%)   12/145 (8.28%) 
Hypertriglyceridaemia † 1     
# participants affected / at risk   11/155 (7.10%)   5/145 (3.45%) 
Hyperuricaemia † 1     
# participants affected / at risk   10/155 (6.45%)   20/145 (13.79%) 
Hypocalcaemia † 1     
# participants affected / at risk   23/155 (14.84%)   27/145 (18.62%) 
Hypokalaemia † 1     
# participants affected / at risk   45/155 (29.03%)   36/145 (24.83%) 
Hypomagnesaemia † 1     
# participants affected / at risk   8/155 (5.16%)   13/145 (8.97%) 
Hyponatraemia † 1     
# participants affected / at risk   6/155 (3.87%)   10/145 (6.90%) 
Hypophosphataemia † 1     
# participants affected / at risk   47/155 (30.32%)   43/145 (29.66%) 
Hypoproteinaemia † 1     
# participants affected / at risk   8/155 (5.16%)   11/145 (7.59%) 
Iron deficiency † 1     
# participants affected / at risk   3/155 (1.94%)   8/145 (5.52%) 
Metabolic acidosis † 1     
# participants affected / at risk   15/155 (9.68%)   10/145 (6.90%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1     
# participants affected / at risk   16/155 (10.32%)   12/145 (8.28%) 
Back pain † 1     
# participants affected / at risk   26/155 (16.77%)   15/145 (10.34%) 
Muscle spasms † 1     
# participants affected / at risk   9/155 (5.81%)   10/145 (6.90%) 
Myalgia † 1     
# participants affected / at risk   10/155 (6.45%)   4/145 (2.76%) 
Pain in extremity † 1     
# participants affected / at risk   14/155 (9.03%)   5/145 (3.45%) 
Nervous system disorders     
Headache † 1     
# participants affected / at risk   25/155 (16.13%)   21/145 (14.48%) 
Tremor † 1     
# participants affected / at risk   10/155 (6.45%)   9/145 (6.21%) 
Psychiatric disorders     
Insomnia † 1     
# participants affected / at risk   35/155 (22.58%)   32/145 (22.07%) 
Sleep disorder † 1     
# participants affected / at risk   21/155 (13.55%)   20/145 (13.79%) 
Renal and urinary disorders     
Bladder pain † 1     
# participants affected / at risk   8/155 (5.16%)   11/145 (7.59%) 
Dysuria † 1     
# participants affected / at risk   7/155 (4.52%)   9/145 (6.21%) 
Haematuria † 1     
# participants affected / at risk   28/155 (18.06%)   31/145 (21.38%) 
Leukocyturia † 1     
# participants affected / at risk   22/155 (14.19%)   18/145 (12.41%) 
Polyuria † 1     
# participants affected / at risk   10/155 (6.45%)   16/145 (11.03%) 
Proteinuria † 1     
# participants affected / at risk   25/155 (16.13%)   25/145 (17.24%) 
Urinary retention † 1     
# participants affected / at risk   11/155 (7.10%)   4/145 (2.76%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1     
# participants affected / at risk   26/155 (16.77%)   29/145 (20.00%) 
Dyspnoea † 1     
# participants affected / at risk   19/155 (12.26%)   17/145 (11.72%) 
Skin and subcutaneous tissue disorders     
Acne † 1     
# participants affected / at risk   14/155 (9.03%)   11/145 (7.59%) 
Hypertrichosis † 1     
# participants affected / at risk   5/155 (3.23%)   8/145 (5.52%) 
Rash † 1     
# participants affected / at risk   8/155 (5.16%)   4/145 (2.76%) 
Vascular disorders     
Haematoma † 1     
# participants affected / at risk   8/155 (5.16%)   8/145 (5.52%) 
Hypertension † 1     
# participants affected / at risk   17/155 (10.97%)   22/145 (15.17%) 
Hypotension † 1     
# participants affected / at risk   22/155 (14.19%)   32/145 (22.07%) 
Lymphocele † 1     
# participants affected / at risk   17/155 (10.97%)   23/145 (15.86%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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