Raltegravir in Patients With End Stage Liver Disease and in Transplant Recipients

• Status: Completed
• Trial end date: 2013-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase I/II, multi-center study is designed to determine the pharmacokinetic profile of Raltegravir in patients with end stage liver disease and to assess drug-drug interaction when Raltegravir is combined with immunosuppressive therapy in liver transplant recipients.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases; French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Raltegravir Potassium

Criteria

Inclusion Criteria:

• Age ≥ 18

• Documented HIV-1 infection, hepatitis B or C co-infection is allowed

• Plasma viral load at screening visit below 50 copies per mL for at least 6 months

• Patient with severe liver failure (Meld Score ≥ 15 and/or refractory ascites and/or haemorrhage of digestive tract and/or hepatic encephalopathy) for taking part into period 1

• Patient eligible for the liver transplant waiting list or immediate post transplantation for taking part into period 2

• Abstinence from alcohol intake for at least 6 months (WHO norm)

• Withdrawal from intravenous drug use for at least 6 months (methadone substitution is permitted)

• No ongoing class C opportunistic infection (1993 CDC classification)

• Patient whose clinical and immunovirological condition allows triple therapy with raltegravir + 2 NRTI or raltegravir + NRTI + enfuvirtide

• Patient whose HIV population, according to cumulative genotypes carried out on viral RNA together with treatment history (if available and interpreted as per the ANRS-AC11 algorithm version no.19) does not present a profile of mutations associated with resistance to raltegravir and is sensitive to at least two fully active* agents selected among nucleoside/nucleotide reverse transcriptase analogs NRTI (abacavir, lamivudine, emtricitabine, tenofovir) or enfuvirtide

*An ARV agent is considered to be fully active if the cumulative genotypes do not show any mutation associated with resistance or any mutation associated with "possible resistance"

• Patient not having experienced viral escape during treatment combining 3TC, FTC or raltegravir

• Patient registered with or covered by a social security scheme

• For women of child-bearing potential, use of a barrier contraceptive method during sexual intercourse and negative pregnancy test (plasma ß-HCG ) at screening visit

• Informed consent form signed at screening visit at the latest

Exclusion Criteria:

• More than two virological failures during antiretroviral treatment

• Currently receiving treatment with an agent in development (apart from an authorization for temporary use)

• Plasma viral load at screening visit ≥ 50 copies per mL during at least the last 6 months

• Pregnant women, or women liable to become pregnant, breast-feeding women, no contraception, or refusal to use contraception

• All conditions (including but not limited to alcohol intake and drug use) liable to compromise, in the investigator's opinion, the safety of treatment and/or the patient's compliance with the protocol

• Patient not having any effective options for NRTI +/- enfuvirtide (defined in the inclusion criteria)

• Ongoing treatment with interferon-alpha or ribavirin for hepatitis C

• Concomitant medication including one or more agents liable to induce UGT1A1 and reduce raltegravir concentrations:

• anti-infective agents: rifampicin/rifampin

• psychotropic/antiepileptic agents: phenytoin, phenobarbital, carbamazepine

• steroidal anti-inflammatory drug: dexamethasone