E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024716 |
E.1.2 | Term | Liver transplantation |
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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 |
• To evaluate the pharmacokinetics of AEB071and primary metabolite, AEE800, in liver transplant patients in the immediate post transplant period
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E.2.2 | Secondary objectives of the trial |
• Evaluate the pharmacokinetics of tacrolimus in the presence of AEB071 • To evaluate the tolerability of AEB071 in liver transplant patients • Evaluate biliary excretion of AEB071and primary metabolite, AEE800, from patients with a T-tube. • Evaluate the relationship of free drug concentration, α-1 acid glycoprotein concentration and pharmacokinetics of AEB071
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female patients of any race, 18 years or older 2. Primary orthotopic liver transplant recipients. 3. Allograft is functioning at an acceptable level by 24 hrs as determined by local investigator 4. Recipients have been initiated on tacrolimus therapy with or without MPA (within 12 hours of transplantation). 5. Females capable of becoming pregnant must have a negative pregnancy test within 7 days prior to enrollment. 6. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent. |
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E.4 | Principal exclusion criteria |
1. Recipients of prior organ transplants or patients recipients of multiple organ transplants (including combined liver- kidney transplantation). 2. Recipients of ABO incompatible transplants. 3. Recipients of living donor or split-liver transplants 4. Transplant with a cold ischemic time of >12 hours. 5. Transplants of donors after cardiac death (DCD). 6. Patients with a MELD-score >35 during 1 month prior transplantation 7. Transplant of a marginal graft into a patient with a MELD-score > 28 defined by any of the following criteria: donor age > 60, CIT > 10h, hypotension periods or inotropic support of the donor, stay on ICU > 3 days, graft steatosis > 30% 8. Patients with acute, fulminant hepatic failure (UNOS I, T1) 9. Patients who are anti-HIV-positive 10. Patients with any past or present malignancy (other than excised basal cell carcinoma and hepato-cellular carcinoma (HCC). 11. Patients with a serum creatinine > 4.0 mg/dL or on dialysis 12. Patients who received any investigational drug within 4 weeks prior to baseline or who are currently enrolled in a clinical trial. 13. Patients who have received or are expected to receive induction antibody or any other immunosuppressive therapy not defined in the protocol. 14. Patients who display hypersensitivity or contraindication to study drugs AEB071, MPA, tacrolimus or corticosteroids. 15. Patients who are requiring the administration of strongly interacting drugs of the CYP450 3A4/5 system ( See Appendix 5). 16. Patients with active or history of clinically significant cardiac abnormalities, for example • Patients requiring drugs with QT-prolonging properties (e.g. antiarrhythmic drugs, such as amiodarone, sotalol, dofetilide, quinidine, procainamide, disopyramide) • Patients with QTcF >470msec (Friderica´s correction), long QT-syndrome (own or with a family history) or with a family history of sudden unexplained death. • Patients with left branch bundle block (LBBB), or who have been hospitalized for heart failure of cardiac etiology in the previous 6 months, have significant and persistent left-ventricular dysfunction (LVEF < 40%), etc. • Patients with a history, in the preceding 3 months, of significant and persistent arrhythmias such as ventricular fibrillation or tachycardia, or atrial fibrillation or flutter. • Patients with symptomatic coronary artery disease • Presence of severe cardiac disease (≥ Old New York Heart Association Classification Grade III), elevated CPK, and/or abnormal ECG, considered by the investigator to be unsafe for the study. 17. Patients with an absolute neutrophil count of < 1,500/mm3, or absolute leukocytes count <2,500/mm3, or platelets < 40’000/mm3. 18. Patients with severe active infection considered by the investigator to be unsafe for the study. 19. Existence of any surgical or medical condition, other than the current transplant, which, in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism, or excretion of the study medication. 20. Abnormal physical or laboratory findings or mental disorders of clinical significance within 2 weeks prior to randomization that, in the opinion of the investigator, might interfere with the objectives of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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
| 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 | 2 |
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 | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 15 |