Case-Control Viramune (Nevirapine) Toxicogenomics Study

July 31, 2013 updated by: Boehringer Ingelheim

A Case-Control Toxicogenomics Study to Identify Unique Genetic Polymorphisms in Patients Who Have Experienced Symptomatic Hepatotoxicity or Severe Cutaneous Toxicity Within the First 8 Weeks of Nevirapine Therapy

Attempt to identify genetic polymorphisms in interrogated pathways which may be associated with symptomatic hepatotoxicity or severe cutaneous toxicity observed in case patients within the first 8 weeks of nevirapine therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

889

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Capital Federal, Argentina
        • 1100.1452.54001 Fundación Huésped
      • Capital Federal, Argentina
        • 1100.1452.54002 Funcei
      • Capital Federal, Argentina
        • 1100.1452.54003 Boehringer Ingelheim Investigational Site
      • Rosario, Argentina
        • 1100.1452.54004 Boehringer Ingelheim Investigational Site
  • Australia
    • New South Wales
      • DarlingHurst, New South Wales, Australia
        • 1100.1452.61005 Boehringer Ingelheim Investigational Site
      • Darlinghurst, New South Wales, Australia
        • 1100.1452.61004 Boehringer Ingelheim Investigational Site
      • Darlinghurst, New South Wales, Australia
        • 1100.1452.61006 Boehringer Ingelheim Investigational Site
    • Queensland
      • Miami, Queensland, Australia
        • 1100.1452.61003 Boehringer Ingelheim Investigational Site
    • Victoria
      • Carlton, Victoria, Australia
        • 1100.1452.61002 Boehringer Ingelheim Investigational Site
      • Melbourne, Victoria, Australia
        • 1100.1452.61008 Boehringer Ingelheim Investigational Site
      • South Yarra, Victoria, Australia
        • 1100.1452.61001 Boehringer Ingelheim Investigational Site
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
        • 1100.1452.01501 St. Paul's Hospital
      • Vancouver, British Columbia, Canada
        • 1100.1452.01504 Boehringer Ingelheim Investigational Site
    • Ontario
      • Toronto, Ontario, Canada
        • 1100.1452.01502 Toronto General Hospital
  • France
      • Bordeaux, France
        • 1100.1452.3304A Hôpital Saint André
      • Lyon, France
        • 1100.1452.3306B Hop Hôtel Dieu
      • Lyon, France
        • 1100.1452.3311B Pavillon P
      • Lyon Cedex 3, France
        • 1100.1452.3311A Hôpital Edouard Herriot
      • Lyon cedex 2, France
        • 1100.1452.3306A Hôpital Hôtel Dieu
      • Lyon cedex 3, France
        • 1100.1452.3311C Hôpital Edouard Herriot
      • Lyon cedex 3, France
        • 1100.1452.3311D Hôpital Edouard Herriot
      • Nantes, France
        • 1100.1452.3305D Hôpital Hôtel Dieu
      • Nantes, France
        • 1100.1452.3305F Hôpital Hôtel Dieu
      • Nantes, France
        • 1100.1452.3305G Hôpital Hôtel Dieu
      • Nantes, France
        • 1100.1452.3305I Hôpital Hôtel Dieu
      • Nantes cedex 1, France
        • 1100.1452.3305A Hôpital hôtel Dieu
      • Nantes cedex 1, France
        • 1100.1452.3305B Hôpital hôtel Dieu
      • Nantes cedex 1, France
        • 1100.1452.3305C Hôpital hôtel Dieu
      • Nantes cedex 1, France
        • 1100.1452.3305E Hôpital hôtel Dieu
      • Nantes cedex 1, France
        • 1100.1452.3305H Hôpital hôtel Dieu
      • Paris, France
        • 1100.1452.3301A Hôpital Saint Louis
      • Paris, France
        • 1100.1452.3303A Hôpital de la Pité Salpêtrière
      • Paris, France
        • 1100.1452.3310A Hôpital Bichat Claude Bernard
      • Paris, France
        • 1100.1452.3310B Hôpital Bichat Claude Bernard
      • Paris, France
        • 1100.1452.3313B Hôpital Saint Antoine
      • Paris, France
        • 1100.1452.3313C Hôpital Saint Antoine
      • Paris, France
        • 1100.1452.3314A Hôpital Européen Georges Pompidou
      • Paris cedex 12, France
        • 1100.1452.3313A Hôpital Saint Antoine
      • Paris cedex 20, France
        • 1100.1452.3302A Hôpital Tenon
      • Toulouse, France
        • 1100.1452.3308B Hôpital Purpan
      • Toulouse cedex 9, France
        • 1100.1452.3308A Hôpital Purpan
      • Tourcoing cedex, France
        • 1100.1452.3307A Hôpital Guy Chateliez
      • Tourcoing cedex, France
        • 1100.1452.3307B Hôpital Guy Chateliez
      • Tourcoing cedex, France
        • 1100.1452.3307C Hôpital Guy Chateliez
      • Tourcoing cedex, France
        • 1100.1452.3307D Hôpital Guy Chateliez
      • Tourcoing cedex, France
        • 1100.1452.3307E Hôpital Guy Chateliez
      • Vandoeuvre les Nancy, France
        • 1100.1452.3312A Hôpital Brabois
  • Germany
      • Berlin, Germany
        • 1100.1452.4901 Boehringer Ingelheim Investigational Site
      • Berlin, Germany
        • 1100.1452.4902 Boehringer Ingelheim Investigational Site
      • Berlin, Germany
        • 1100.1452.9907 Boehringer Ingelheim Investigational Site
      • Bochum, Germany
        • 1100.1452.4903 Boehringer Ingelheim Investigational Site
      • Bonn, Germany
        • 1100.1452.4918 Boehringer Ingelheim Investigational Site
      • Düsseldorf, Germany
        • 1100.1452.4912 Boehringer Ingelheim Investigational Site
      • Essen, Germany
        • 1100.1452.4904 Boehringer Ingelheim Investigational Site
      • Frankfurt am Main, Germany
        • 1100.1452.4933 Boehringer Ingelheim Investigational Site
      • Hamburg, Germany
        • 1100.1452.4916 Boehringer Ingelheim Investigational Site
      • Hamburg, Germany
        • 1100.1452.4931 Boehringer Ingelheim Investigational Site
      • München, Germany
        • 1100.1452.4910 Boehringer Ingelheim Investigational Site
      • Ulm, Germany
        • 1100.1452.4900 Universitätsklinikum Ulm
      • Würzburg, Germany
        • 1100.1452.4932 Boehringer Ingelheim Investigational Site
  • Netherlands
      • Amsterdam, Netherlands
        • 1100.1452.31001 Academisch Medisch Centrum
      • Amsterdam, Netherlands
        • 1100.1452.31002 Onze Lieve Vrouwen Gasthuis
  • Spain
      • Badalona, Spain
        • 1100.1452.34005 Boehringer Ingelheim Investigational Site
      • Barcelona, Spain
        • 1100.1452.34001 Boehringer Ingelheim Investigational Site
      • Barcelona, Spain
        • 1100.1452.34002 Boehringer Ingelheim Investigational Site
      • Barcelona, Spain
        • 1100.1452.34004 Boehringer Ingelheim Investigational Site
      • L'Hospitalet de Llobregat, Spain
        • 1100.1452.34003 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1100.1452.34006 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1100.1452.34007 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1100.1452.34010 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1100.1452.34011 Boehringer Ingelheim Investigational Site
      • Sevilla, Spain
        • 1100.1452.34009 Boehringer Ingelheim Investigational Site
  • Taiwan
      • Kaohsiung, Taiwan
        • 1100.1452.88602 Kaohsiung Veterans General Hospital
      • Kaohsiung, Taiwan
        • 1100.1452.88603 E-Da Hospital
      • Kaohsiung, Taiwan
        • 1100.1452.88605 Chung-Ho Memorial Hospital, Kaohsiung Medical University
      • Taichung, Taiwan
        • 1100.1452.88606 China Medical University Hospital
      • Taipei, Taiwan
        • 1100.1452.88601 National Taiwan University Hospital
      • Taipei, Taiwan
        • 1100.1452.88604 Taipei City Hospital
  • Thailand
      • Bangkok, Thailand
        • 1100.1452.66001 Boehringer Ingelheim Investigational Site
      • Bangkok, Thailand
        • 1100.1452.66002 Boehringer Ingelheim Investigational Site
      • Khon Kaen, Thailand
        • 1100.1452.66003 Boehringer Ingelheim Investigational Site
  • United Kingdom
      • Birmingham, United Kingdom
        • 1100.1452.44006 Boehringer Ingelheim Investigational Site
      • Brighton, United Kingdom
        • 1100.1452.44004 Boehringer Ingelheim Investigational Site
      • Coventry, United Kingdom
        • 1100.1452.44001 Boehringer Ingelheim Investigational Site
      • London, United Kingdom
        • 1100.1452.44002 Boehringer Ingelheim Investigational Site
      • London, United Kingdom
        • 1100.1452.44005 Boehringer Ingelheim Investigational Site
      • London, United Kingdom
        • 1100.1452.44008 Boehringer Ingelheim Investigational Site
      • London, United Kingdom
        • 1100.1452.44009 Boehringer Ingelheim Investigational Site
      • Manchester, United Kingdom
        • 1100.1452.44003 Boehringer Ingelheim Investigational Site
      • Plaistow, London, United Kingdom
        • 1100.1452.44007 Boehringer Ingelheim Investigational Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States
        • 1100.1452.01006 Boehringer Ingelheim Investigational Site
    • Colorado
      • Denver, Colorado, United States
        • 1100.1452.01013 Boehringer Ingelheim Investigational Site
    • Connecticut
      • Baltimore, Connecticut, United States
        • 1100.1452.99999 Boehringer Ingelheim Investigational Site
      • New Haven, Connecticut, United States
        • 1100.1452.01011 Boehringer Ingelheim Investigational Site
    • Maryland
      • Baltimore, Maryland, United States
        • 1100.1452.01003 Boehringer Ingelheim Investigational Site
    • Massachusetts
      • Boston, Massachusetts, United States
        • 1100.1452.01002 Boehringer Ingelheim Investigational Site
      • Springfield, Massachusetts, United States
        • 1100.1452.01014 Boehringer Ingelheim Investigational Site
    • Missouri
      • St. Louis, Missouri, United States
        • 1100.1452.01015 Boehringer Ingelheim Investigational Site
    • New York
      • New York, New York, United States
        • 1100.1452.01016 Boehringer Ingelheim Investigational Site
    • North Carolina
      • Chapel hill, North Carolina, United States
        • 1100.1452.01012 Boehringer Ingelheim Investigational Site
    • Tennessee
      • Nashville, Tennessee, United States
        • 1100.1452.01001 Boehringer Ingelheim Investigational Site
    • Texas
      • Fort Worth, Texas, United States
        • 1100.1452.01004 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients Who Have Experienced Symptomatic Hepatotoxicity or Severe Cutaneous Toxicity Within the First 8 Weeks of Nevirapine Therapy

Description

Inclusion Criteria:

Inclusion for Case

  1. Male or female patients >=18 years of age with HIV-1 infection who experienced one or more of the following adverse reactions within the first 8 weeks of starting nevirapine therapy:

    • Grade 3 or 4 LFT elevation (ALT or AST > 5X ULN) and any symptom consistent with clinical hepatitis (see Appendix 10.1)
    • Acute liver failure secondary to nevirapine therapy*
    • Functional group III or IV rash
    • *Acute liver failure is defined as serious liver injury usually requiring hospitalization that may lead to death or liver transplantation.

    Inclusion for Control

  2. Male or female patients >=18 years of age with HIV-1 infection who have been exposed to nevirapine therapy for at least 18 weeks and who do not meet any of the case inclusion criteria

Exclusion Criteria:

Exclusion for Cases

  1. Patients with any hepatotoxicity or rash event which in the investigators judgement is not related to nevirapine use (ex. hepatotoxicity due to alcohol or other medicinal use or rash due to other medicinal use).
  2. Patients who began abacavir or TMP-SMX (trimethoprim/sulfamethoxazole) therapy 2 weeks or less prior to or up to 8 weeks after initiating nevirapine therapy.

  3. Patients with AST or ALT elevations > 5 times the ULN (>= Grade 3) just prior to the initiation of nevirapine therapy.

    Exclusion for Controls

  4. Patients who discontinued nevirapine before completing 18 weeks of dosing with 200 mg/day for 2 weeks followed by 400 mg/day thereafter.
  5. Patients who developed functional group I, IIa or IIb rash within 18 weeks of starting nevirapine therapy, or any dermatologic condition that could plausibly be attributed to nevirapine.
  6. Patients with ALT or AST elevations >2.5 X ULN (>Grade 1) within 18 weeks of starting nevirapine therapy.
  7. Any hepatobiliary adverse event that could possibly be attributed to nevirapine.

  8. Patients who develop any systemic reaction attributable to nevirapine use during the first 18 weeks of nevirapine treatment such as flu-like symptoms, arthralgia, myalgia, or conjunctivitis.

    Exclusion for Cases and Controls

  9. Patients who have participated in the 2NN-Long-term Follow-up study (1100.1454)
  10. Patients with CD4 count 150 cells/mm3 prior to the initiation of nevirapine therapy (last available result measured 6 months prior to the initiation of nevirapine therapy).
  11. Evidence of acute co-infection with viral hepatitis.
  12. Patients taking prednisone, prednisolone, or immuno-modulatory medication within the first 8 weeks of nevirapine therapy.
  13. Patients who are unwilling to provide blood samples for DNA testing.
  14. Patients who did not sign informed consent and or authorization to release protected health information per local requirements.
  15. Patients without available liv

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
All study population
Drug: Nevirapine
Patients with HIV-1 infection who have taken or are currently taking nevirapine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Endpoints: relationship between nevirapine-related AEs and genetic polymorphisms loci: Drug metabolizing enzymes (e.g., cytochrome P450 isoforms) Drug transporters (e.g., MDR1 and OATP-C) Human Major Histocompatibility Complex region genes

Secondary Outcome Measures

Outcome Measure
Descriptive demographics comparing cases with matched controls in an attempt to link genetic polymorphisms associated with symptomatic hepatotoxicity or severe cutaneous toxicity (cases) to gender, race or other patient characteristics.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2006

Primary Completion (Actual)

September 1, 2008

Study Registration Dates

First Submitted

March 28, 2006

First Submitted That Met QC Criteria

April 2, 2006

First Posted (Estimate)

April 5, 2006

Study Record Updates

Last Update Posted (Estimate)

August 1, 2013

Last Update Submitted That Met QC Criteria

July 31, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1100.1452
  • 2005-004321-26

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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