E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
de novo heart transplantation |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess if comparable rates of the composite efficacy failure (biopsy-proven acute rejection of ISHLT grade ≥ 3A, acute rejection episodes associated with hemodynamic compromise, graft loss/re-transplant, death, or loss to follow-up) are achieved in cohorts of de novo heart recipients treated with Certican-reduced Neoral versus MMF-Neoral standard dose at 12 months after initial dose of study medication |
|
E.2.2 | Secondary objectives of the trial |
• To assess incidence rate of graft loss/re-transplant, death or loss to follow-up at 12 months • To demonstrate that similar renal function assessed by calculated GFR by MDRD formula (Coresh et. al. 2003) is achieved in the Certican treatment arm compared to the MMF treatment arm within 12 months of initial dose of study medication.
• IVUS sub-study analysis (sub-study performed only in selected centers) - To evaluate the change in average maximum intimal thickness from Baseline and the incidence of chronic rejection (allograft vasculopathy) in patients receiving CERTICAN 1.5mg/d and those receiving MMF as measured by intravascular ultrasound (IVUS) at 12 months.
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Male or female cardiac recipients 18-70 years of age undergoing primary heart transplantation. • Patients who have given written informed consent to participate in the study.
|
|
E.4 | Principal exclusion criteria |
•Calculated creatinine clearance <40 ml/min at screening (MDRD Formula) •Patients with platelet count <50,000/mm at the evaluation before randomization. •Patients who are recipients of multiple solid organ transplants. •Patients who are recipients of ABO incompatible transplants •Patients with active systemic infection. •Patients receiving drugs used for non-approved indications in the 30 days prior to study entry. •Patients receiving induction therapy in non induction center •Patients not receiving induction therapy in an induction center •Induction therapy other than Simulect •Presence of severe hypercholesterolemia (≥350 mg/dL; ≥9 mmol/L) or hypertriglyceridemia (≥ 750 mg/dL; ≥8.5 mmol/L) before randomization. •Patients with an absolute neutrophil count of ≤1,500/mm3 or white blood cell count of ≤ 4000/mm3 at baseline before surgery •Patients with a history of significant coagulopathy or medical condition requiring long term anti-coagulation after transplantation (low dose aspirin treatment is allowed) •Patients who are HIV-positive or Hepatitis C (PCR+ only) or B surface antigen positive. Laboratory results obtained within 6 months prior to study entry are acceptable. •Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C (PCR+ only) are excluded •Patients being treated with terfenadine, astemoizole, or cisapride •Patients with any past (within the past 5 years) or present malignancy (other than excised basal cell carcinoma) •Patients with a known hypersensitivity to drugs of this class. •Patients with donor greater than 65 years and/or with known donor heart disease at the time of transplant. •Patients who are treated with drugs strong inducers or inhibitors of cytochrome P450 3A4. •Cold ischemia time >6 hours. •Unable to take oral medication.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to show that Certican is non-inferior to the MMF treatment arm, with respect to primary efficacy failure rate at 12 months
To test non-inferiority of Certican 1.5mg dose to MMF |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |