A Pharmacokinetic Study to Assess Nevirapine [Viramune] Levels in HIV Infected Patients With Impaired Hepatic Functions

A Pharmacokinetic Study to Assess Nevirapine Levels in HIV-infected Patients With Impaired Hepatic Function

The objective of this study was to evaluate the steady-state clearance of nevirapine among HIV-1 positive patients with hepatic fibrosis, and to examine whether the degree of hepatic impairment influences clearance.

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency; HIV Infections
• Intervention / Treatment: Drug: nevirapine

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Lyon cedex 02, France
    • Hopital de l'Hotel Dieu
  • Paris, France
    • Hopital Pitie Salpetriere
• Spain
  • Barcelona, Spain
    • Hospital Clínico y Provincial de Barcelona - HIV
• United States
  • California
    • Bakersfield, California, United States
      • Boehringer Ingelheim Investigational Site
    • San Francisco, California, United States
      • California Pacific Medical Center
    • San Francisco, California, United States
      • Boehringer Ingelheim Investigational Site
  • New York
    • Albany, New York, United States
      • Albany Medical College, MC 142
  • Rhode Island
    • Providence, Rhode Island, United States
      • Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION

1. Male or female subjects >=18 years of age with HIV-1 infection and chronic liver disease as reflected by a documented biopsy with hepatic fibrosis present.

2. a. Participants must be receiving nevirapine 200 mg twice daily as part of a stable ARV regimen for a minimum of 6 weeks prior to trough level sample collection.

   b. Participants receiving nevirapine 400 mg once daily as part of a stable ARV regimen for a minimum of 6 weeks, who are willing to switch to nevirapi0 mg twice daily for a minimum of 14 days prior to trough collection.

3. Participants must have uoxylin and Eosin (H and E) stained slide and one trichrome stained pathology slide available at the time of enrollment. There is no time restriction on liver biopsy slides that pathologically confirm the presence of cirrhosis. The presence of cirrhosis must be documented on the liver biopsy report.

EXCLUSION

1. Current (within the past 4 weeks) HIV antiviral therapy with other NNRTI's.

2. Concurrent use (within the past 7 days) of any of the following:

   1. Systemic azole antifungal agents (fluconazole, itraconazole, ketoconazole, etc.)
   2. Clarithromycin
   3. Rifampin
   4. St John's Wort
3. Inability to provide a blood sample.
4. Patients who have evidence for hepatic or other encephalopathy above Grade 1
5. Patients with renal failure who require dialysis.
6. Pregnant and/or breast feeding women..

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoints are the degree of hepatic impairment, steady state nevirapine clearance, and the increase in estimated clearance when trough is supplemented by plasma levels measured one, two and four hours after nevirapine administration	Up to 4 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma levels of nevirapine metabolites of all patients and Child-Pugh scores among patients with cirrhosis.	Up to 14 hours

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim Study Coordinator, Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2004
• Primary Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: September 2, 2005
• First Submitted That Met QC Criteria: September 2, 2005
• First Posted (Estimated): September 5, 2005

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine
• Other Study ID Numbers: 1100.1448