An open-label, two-period, multi-center, single dose study to assess the pharmacokinetics of AEB071 in de novo liver transplant patients - ND

• Conditions: liver transplant; MedDRA version: 6.1Level: PTClassification code 10024714

• Registration Number: EUCTR2007-001361-15-IT
• Lead Sponsor: OVARTIS FARMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-11-12
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Male and female patients of any race, 18 years or older Primary orthotopic liver transplant recipients. Allograft is functioning at an acceptable level by 24 hrs as determined by local investigator Recipients have been initiated on tacrolimus therapy (within 12 hours of transplantation). Females capable of becoming pregnant must have a negative pregnancy test within 7 days prior to enrollment. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion criteria Recipients of prior organ transplants or patients recipients of multiple organ transplants (including combined liver- kidney transplantation). Recipients of ABO incompatible transplants. Recipients of living donor transplants or split liver transplants Transplant with a cold ischemic time of >12 hours. Transplants of donors after cardiac death (DCD). Patients with a MELD-score >35 during 1 month prior transplantation 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% Patients with acute, fulminant hepatic failure (UNOS I, T1) Patients who are anti-HIV-positive Patients with any past or present malignancy (other than excised basal cell carcinoma and hepatocellular carcinoma (HCC). Patients with a serum creatinine > 4.0 mg/dL or on dialysis Patients who received any investigational drug within 4 weeks prior to baseline or who are currently enrolled in a clinical trial. Patients who have received or are expected to receive induction antibody or any other immunosuppressive therapy not defined in the protocol. Patients who display hypersensitivity or contraindication to study drugs AEB071, tacrolimus or corticosteroids. Patients who are requiring the administration of strongly interacting drugs of the CYP450 3A4/5 system (see Appendix 5). Patients with active or a history of clinically significant cardiac abnormalities, such as: Left branch bundle block (LBBB), hospitalized in the previous 6 months for heart failure of cardiac etiology, significant and persistent left-ventricular dysfunction (LVEF < 40%), etc. Patients requiring drugs with QT-prolonging properties (e.g. antiarrhythmic drugs, such as amiodarone, sotalol, dofetilide, quinidine, procainamide, disopyramide)PLS SEE PROOCOL

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary objective(s) To evaluate the pharmacokinetics of AEB071 and primary metabolite, AEE800, in liver transplant patients in the immediate post transplant period To evaluate the safety and tolerability of AEB071 in liver transplant patients;Secondary Objective: Secondary objective(s) Evaluate the pharmacokinetics of tacrolimus in the presence of AEB071 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;Primary end point(s): The primary end point of this study is to evaluate the pharmacokinetics of AEB071 and primary metabolite, AEE800, in liver transplant patients in the immediate post transplant period. As a statistical analysis to support the primary end point, geometric mean estimates of AUC0-t, AUC0-∞ and Cmax and their 90% confidence intervals will be calculated for both periods.