E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Renal allograft transplantation |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066543 |
E.1.2 | Term | Acute allograft rejection |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Demonstrate that at least one of the sotrastaurin treatment arms is non-inferior to the active control regimen myfortic + tacrolimus with respect to composite efficacy failure (treated BPAR of grade IA or higher, graft loss, death or lost to follow up) at Month 6 post-transplantation |
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E.2.2 | Secondary objectives of the trial |
• Evaluate renal function at Months 6, 12, 24 and 36 post-Tx using
o eGFR by formula,
o a composite renal function EP defined as eGFR-MDRD < 60 mL/min/1.73 m2 at Month 12, or a decrease from Month 3 to Month 12 ≥ 10 mL/min/1.73 m2 in each sotrastaurin treatment arm relative to the control regimen (Month 12),
o estimated creatinine clearance (Cockcroft-Gault formula).
• Evaluate the composite efficacy endpoint in the sotrastaurin arms and the control arm at Months 12, 24 and 36 post-Tx.
• Evaluate individual components (and combinations of the individual components) of the composite efficacy endpoint in the sotrastaurin arms and the control arm at Months 6, 12, 24 and 36 post-Tx.
• Evaluate safety and tolerability between the sotrastaurin arms and the control arm, including infections, GI tolerability, ECG parameters, and hematological parameters (e.g. neutrophils) at Months 6, 12, 24 and 36 post-Tx. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Protocol post-text supplement: 1 - Pharmacokinetic substudy
10-Sep-2009, v 1
This PK substudy is designed primarily to characterize the longitudinal, steady-state PK of sotrastaurin in de novo renal transplant recipients receiving sotrastaurin at dose levels of 100 mg, 200 mg and 300 mg twice-daily. The secondary objectives are twofold: to characterize the PK of the concomitant immunosuppressants tacrolimus and mycophenolic acid (MPA) and to assess the correlation between blood and plasma concentrations of sotrastaurin. |
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E.3 | Principal inclusion criteria |
• Male or female patients ≥ 18 years old.
• 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. |
|
E.4 | Principal exclusion criteria |
• Recipients who are unable to receive the first dose of oral study medication within 24 hours after allograft reperfusion.
• 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 (unless lost due to surgical complication).
• Patients who are treated with drugs that are strong inducers or inhibitors of CYP3A4 at screening and cannot discontinue this treatment.
• Patients with long QT-syndrome, or QTcF at baseline exceeding 500 msec, or who are treated with drugs inducing QT prolongation at screening, and cannot discontinue this treatment.
• Patients requiring antiarrhythmic drugs with QT-prolonging properties (class 1a and class 3).
• Patients with a family history of long QT syndrome or of sudden unexplained death.
• Patients with a history, in the preceding 3 months of significant and persistent arrhythmias such as ventricular fibrillation or tachycardia, atrial fibrillation or flutter.
• Patients with symptomatic/unstable coronary artery disease (i.e. angina, untreated cardiac atherosclerotic disease) requiring hospitalization or a revascularization procedure in the 30 days prior to randomization.
• Patients with chronic heart failure which required hospitalization in the 30 days prior to randomization.
• Patients at high immunological risk, e.g., sensitized patients (most recent anti-HLA class I panel reactive antibodies (PRA) > 20% by a CDC-based assay or > 50% by a flow cytometry, Luminex or enzyme linked immunosorbant assay (ELISA)). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is defined as a composite of treated BPAR (tBPAR) of grade IA or higher, graft loss, death or lost to follow-up) based on the FAS. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 56 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of study visist at month 36 |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |