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Case-Control Viramune (Nevirapine) Toxicogenomics Study

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00310843
First received: March 28, 2006
Last updated: July 31, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Nevirapine
Phase 4

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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:
  • 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.

Enrollment: 889
Study Start Date: February 2006
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
All study population Drug: Nevirapine
Patients with HIV-1 infection who have taken or are currently taking nevirapine

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00310843

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

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00310843     History of Changes
Other Study ID Numbers: 1100.1452, 2005-004321-26
Study First Received: March 28, 2006
Last Updated: July 31, 2013
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Responsilble Ethics Committee
Canada: Health Canada-Protocol Review not required
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Germany: BfArM-Bundesinstitut fuer Arzneimittel und Medizinprodukte (Federal Authoriteis for Drugs and Medical Devices)
Great Britain: MHRA
Netherlands: AMC (Academisch Medisch Centrum)
Spain: Spanish Agency for Medicines and Health Products
Taiwan: Department of Health, Executive Yuan, Taiwan
Thailand: Ministry of Public Health
United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Nevirapine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014