Efficacy, Safety, Tolerability, and Pharmacokinetics of Sotrastaurin Combined With Tacrolimus vs. a Mycophenolic Acid-tacrolimus Regimen in Renal Transplant Patients

Study Overview
=================
Brief Summary
-----------------
This study will assess the safety and efficacy of different doses of sotrastaurin when combined with tacrolimus for the prevention of acute rejection after de novo renal transplantation.

Official Title
-----------------
A Partially Blinded, Prospective, Randomized Multicenter Study Evaluating Efficacy, Safety and Tolerability of Oral Sotrastaurin Plus Standard or Reduced Exposure Tacrolimus vs. Mycophenolic Acid Plus Tacrolimus in de Novo Renal Transplant Recipients

Conditions
-----------------
Renal Transplantation

Intervention / Treatment
-----------------
* Drug: sotrastaurin (Dose 1) + tacrolimus + standard of care medications
* Drug: sotrastaurin (Dose 2) + tacrolimus + standard of care medications
* Drug: sotrastaurin (Dose 3) + tacrolimus + standard of care medications
* Drug: mycophenolic acid + tacrolimus + standard of care medications


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Recipients of a first or second kidney transplant from a deceased, living unrelated or non-human leukocyte antigen (HLA) identical living related donor. Recipients of a kidney with a cold ischemia time < 30 hours. Recipients of a kidney from a donor 10 - 65 years old. Exclusion criteria: Multi-organ transplant recipients. Recipients of an organ from an non-heart beating donor. Patients receiving a second kidney allograft if the first allograft was Functional for less than three years Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) at screening and cannot discontinue this treatment. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>sotrastaurin (100mg bid) + tacrolimus + standard of care medications | Drug: sotrastaurin (Dose 1) + tacrolimus + standard of care medications<br>* sotrastaurin (100mg bid) + tacrolimus + standard of care medications<br>|
| Experimental: Arm 2<br>sotrastaurin (200mg bid) + tacrolimus + standard of care medications | Drug: sotrastaurin (Dose 2) + tacrolimus + standard of care medications<br>* sotrastaurin (200mg bid) + tacrolimus + standard of care medications<br>|
| Experimental: Arm 3<br>sotrastaurin (300mg bid) + tacrolimus + standard of care medications | Drug: sotrastaurin (Dose 3) + tacrolimus + standard of care medications<br>* sotrastaurin (300mg bid) + tacrolimus + standard of care medications<br>|
| Active Comparator: Arm 4<br>mycophenolic acid (720mg bid) + tacrolimus + standard of care medications | Drug: mycophenolic acid + tacrolimus + standard of care medications<br>* mycophenolic acid (720mg bid) + tacrolimus + standard of care medications<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrate that at least one of the sotrastaurin + tacrolimus treatment arms is non-inferior to the active control regimen with respect to composite efficacy failure (treated BPAR of grade IA or higher, graft loss, death or lost to follow up). |  | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate renal allograft function post-transplantation (estimated GFR by MDRD equation; estimated creatinine clearance by Cockroft-Gault formula; serum creatinine) |  | Months 6, 12, 24, and 36 | 
| Demonstrate that at least one of the sotrastaurin + tacrolimus treatment arms is non-inferior to the active control regimen with respect to composite efficacy failure (treated BPAR of grade IA or higher, graft loss, death or lost to follow up). |  | Months 12, 24, and 36 | 
| Evaluate individual components of the composite efficacy endpoint (treated BPAR, severity of acute rejections by Banff 2007 diagnostic category). |  | Months 6, 12, 24, and 36 | 
| Evaluate safety and tolerability (adverse events, serious adverse events, laboratory abnormalities, vital signs, electrocardiograms, physical examination). |  | Months 6, 12, 24, and 36 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Renal transplantation