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

NCT01022476 | Completed Phase 1 DMC

• 2 other identifiers: 2009-014616-36ANRS 148 LIVERAL
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infection; Liver Failure; Evidence of Liver Transplantation

Keywords

Pharmacokinetics; Raltegravir; Immunosuppressive Agents; Severe hepatic insufficiency; Liver Transplantation; Additional Keywords; HIV Infection; Hepatocarcinoma; Hepatitis C; Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic parameters of raltegravir in patients with severe liver dysfunction and after a liver transplantation when combined to immunosuppressive therapy. Pharmacokinetic parameters of immunosuppressive drugs with or without raltegravir

  at month 1 for period 1 and day 7-month 1 for period 2

Secondary Outcomes (4)

• To assess the maintenance of the virological efficacy on HIV of raltegravir combined with two fully active molecules among NRTI (or NRTI + enfuvirtide). Follow-up over a 3-months period before and after transplantation

  from day 0 to month 3 for period 1 and period 2

• To assess the safety of raltegravir before transplantation in patients with impaired liver function, and after transplantation in combination with immunosuppressive treatment

  from day 0 to month 3 for period 1 and period 2

• To describe the clinical outcome of patients (such as the onset of opportunistic infections, relapse of HCV infection, morphological and metabolic disorders outcomes)

  from day 0 to month 3 for period 1 and period 2

• To describe the changes in liver function (evaluation of liver function during treatment) before and after liver transplantation

  from day 0 to month 3 for period 1 and period 2

Study Arms (1)

Raltegravir potassium

EXPERIMENTAL

raltegravir 400 mg twice a day

Drug: Raltegravir potassium

Interventions

Raltegravir potassium DRUG

one pill of raltegravir 400 mg twice a day

Also known as: ISENTRESS

Raltegravir potassium

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Service de Médecine Interne, Hôpital de Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Related Links

• Agence nationale de recherches sur le sida et les hépatites virales

MeSH Terms

Conditions

HIV Infections; Liver Failure; Hepatic Insufficiency; Carcinoma, Hepatocellular; Hepatitis C; Hepatitis B

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Liver Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Hepatitis, Viral, Human; Flaviviridae Infections; Hepatitis; Hepadnaviridae Infections; DNA Virus Infections

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Elina TEICHER, MD

  Hôpital de Bicêtre - LE KREMLIN-BICETRE - FRANCE

  PRINCIPAL INVESTIGATOR

• Jean-Pierre ABOULKER, MD

  INSERM SC10 VILLEJUIF FRANCE

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2009
• First Posted: December 1, 2009
• Study Start: May 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: July 18, 2013

Record last verified: 2013-07

Locations

FR (1)