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

• Conditions: liver transplant; MedDRA version: 9.1Level: LLTClassification code 10024716Term: Liver transplantation

• Registration Number: EUCTR2007-001361-15-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05-06
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

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

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.
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) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: • To evaluate the pharmacokinetics of AEB071and primary metabolite, AEE800, in liver transplant patients in the immediate post transplant period<br>;Secondary Objective: • Evaluate the pharmacokinetics of tacrolimus in the presence of AEB071<br>• To evaluate the tolerability of AEB071 in liver transplant patients<br>• Evaluate biliary excretion of AEB071and primary metabolite, AEE800, from patients with a T-tube.<br>• Evaluate the relationship of free drug concentration, a-1 acid glycoprotein concentration and pharmacokinetics of AEB071<br>;Primary end point(s): n.a. PK study only