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
No text entered.

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.
No text entered.

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  
Number of Participants  
[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     145/145  
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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  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided by Novartis

Publications automatically indexed to this study:

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00154310     History of Changes
Other Study ID Numbers: CRAD001A2418
Study First Received: September 8, 2005
Results First Received: January 11, 2011
Last Updated: October 21, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices