Case-Control Viramune (Nevirapine) Toxicogenomics Study

NCT00310843 | Completed

• 2 other identifiers: 1100.14522005-004321-26
• Study Type: observational
• Target: 889
• Locations: 11 countries
• Sites: 102

Brief Summary

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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.

Study Arms (1)

All study population

Drug: Nevirapine

Interventions

Nevirapine DRUG

Patients with HIV-1 infection who have taken or are currently taking nevirapine

All study population

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.
• Patients with AST or ALT elevations \> 5 times the ULN (\>= Grade 3) just prior to the initiation of nevirapine therapy.
• Patients who discontinued nevirapine before completing 18 weeks of dosing with 200 mg/day for 2 weeks followed by 400 mg/day thereafter.
• 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.
• Patients with ALT or AST elevations \>2.5 X ULN (\>Grade 1) within 18 weeks of starting nevirapine therapy.
• Any hepatobiliary adverse event that could possibly be attributed to nevirapine.
• 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.
• Patients who have participated in the 2NN-Long-term Follow-up study (1100.1454)
• 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).
• Evidence of acute co-infection with viral hepatitis.
• Patients taking prednisone, prednisolone, or immuno-modulatory medication within the first 8 weeks of nevirapine therapy.
• Patients who are unwilling to provide blood samples for DNA testing.
• Patients who did not sign informed consent and or authorization to release protected health information per local requirements.
• Patients without available liv

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (102)

1100.1452.01006 Boehringer Ingelheim Investigational Site

Birmingham, Alabama, United States

Location

1100.1452.01013 Boehringer Ingelheim Investigational Site

Denver, Colorado, United States

Location

1100.1452.99999 Boehringer Ingelheim Investigational Site

Baltimore, Connecticut, United States

Location

1100.1452.01011 Boehringer Ingelheim Investigational Site

New Haven, Connecticut, United States

Location

1100.1452.01003 Boehringer Ingelheim Investigational Site

Baltimore, Maryland, United States

Location

1100.1452.01002 Boehringer Ingelheim Investigational Site

Boston, Massachusetts, United States

Location

1100.1452.01014 Boehringer Ingelheim Investigational Site

Springfield, Massachusetts, United States

Location

1100.1452.01015 Boehringer Ingelheim Investigational Site

St Louis, Missouri, United States

Location

1100.1452.01016 Boehringer Ingelheim Investigational Site

New York, New York, United States

Location

1100.1452.01012 Boehringer Ingelheim Investigational Site

Chapel Hill, North Carolina, United States

Location

1100.1452.01001 Boehringer Ingelheim Investigational Site

Nashville, Tennessee, United States

Location

1100.1452.01004 Boehringer Ingelheim Investigational Site

Fort Worth, Texas, United States

Location

1100.1452.54001 Fundación Huésped

Capital Federal, Argentina

Location

1100.1452.54002 Funcei

Capital Federal, Argentina

Location

1100.1452.54003 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1100.1452.54004 Boehringer Ingelheim Investigational Site

Rosario, Argentina

Location

1100.1452.61004 Boehringer Ingelheim Investigational Site

Darlinghurst, New South Wales, Australia

Location

1100.1452.61005 Boehringer Ingelheim Investigational Site

Darlinghurst, New South Wales, Australia

Location

1100.1452.61006 Boehringer Ingelheim Investigational Site

Darlinghurst, New South Wales, Australia

Location

1100.1452.61003 Boehringer Ingelheim Investigational Site

Miami, Queensland, Australia

Location

1100.1452.61002 Boehringer Ingelheim Investigational Site

Carlton, Victoria, Australia

Location

1100.1452.61008 Boehringer Ingelheim Investigational Site

Melbourne, Victoria, Australia

Location

1100.1452.61001 Boehringer Ingelheim Investigational Site

South Yarra, Victoria, Australia

Location

1100.1452.01501 St. Paul's Hospital

Vancouver, British Columbia, Canada

Location

1100.1452.01504 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1100.1452.01502 Toronto General Hospital

Toronto, Ontario, Canada

Location

1100.1452.3304A Hôpital Saint André

Bordeaux, France

Location

1100.1452.3306A Hôpital Hôtel Dieu

Lyon, France

Location

1100.1452.3306B Hop Hôtel Dieu

Lyon, France

Location

1100.1452.3311A Hôpital Edouard Herriot

Lyon, France

Location

1100.1452.3311B Pavillon P

Lyon, France

Location

1100.1452.3311C Hôpital Edouard Herriot

Lyon, France

Location

1100.1452.3311D Hôpital Edouard Herriot

Lyon, France

Location

1100.1452.3305A Hôpital hôtel Dieu

Nantes, France

Location

1100.1452.3305B Hôpital hôtel Dieu

Nantes, France

Location

1100.1452.3305C Hôpital hôtel Dieu

Nantes, France

Location

1100.1452.3305D Hôpital Hôtel Dieu

Nantes, France

Location

1100.1452.3305E Hôpital hôtel Dieu

Nantes, France

Location

1100.1452.3305F Hôpital Hôtel Dieu

Nantes, France

Location

1100.1452.3305G Hôpital Hôtel Dieu

Nantes, France

Location

1100.1452.3305H Hôpital hôtel Dieu

Nantes, France

Location

1100.1452.3305I Hôpital Hôtel Dieu

Nantes, France

Location

1100.1452.3301A Hôpital Saint Louis

Paris, France

Location

1100.1452.3302A Hôpital Tenon

Paris, France

Location

1100.1452.3303A Hôpital de la Pité Salpêtrière

Paris, France

Location

1100.1452.3310A Hôpital Bichat Claude Bernard

Paris, France

Location

1100.1452.3310B Hôpital Bichat Claude Bernard

Paris, France

Location

1100.1452.3313A Hôpital Saint Antoine

Paris, France

Location

1100.1452.3313B Hôpital Saint Antoine

Paris, France

Location

1100.1452.3313C Hôpital Saint Antoine

Paris, France

Location

1100.1452.3314A Hôpital Européen Georges Pompidou

Paris, France

Location

1100.1452.3308A Hôpital Purpan

Toulouse, France

Location

1100.1452.3308B Hôpital Purpan

Toulouse, France

Location

1100.1452.3307A Hôpital Guy Chateliez

Tourcoing, France

Location

1100.1452.3307B Hôpital Guy Chateliez

Tourcoing, France

Location

1100.1452.3307C Hôpital Guy Chateliez

Tourcoing, France

Location

1100.1452.3307D Hôpital Guy Chateliez

Tourcoing, France

Location

1100.1452.3307E Hôpital Guy Chateliez

Tourcoing, France

Location

1100.1452.3312A Hôpital Brabois

Vandœuvre-lès-Nancy, France

Location

1100.1452.4901 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1100.1452.4902 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1100.1452.9907 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1100.1452.4903 Boehringer Ingelheim Investigational Site

Bochum, Germany

Location

1100.1452.4918 Boehringer Ingelheim Investigational Site

Bonn, Germany

Location

1100.1452.4912 Boehringer Ingelheim Investigational Site

Düsseldorf, Germany

Location

1100.1452.4904 Boehringer Ingelheim Investigational Site

Essen, Germany

Location

1100.1452.4933 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

Location

1100.1452.4916 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1100.1452.4931 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1100.1452.4910 Boehringer Ingelheim Investigational Site

München, Germany

Location

1100.1452.4900 Universitätsklinikum Ulm

Ulm, Germany

Location

1100.1452.4932 Boehringer Ingelheim Investigational Site

Würzburg, Germany

Location

1100.1452.31001 Academisch Medisch Centrum

Amsterdam, Netherlands

Location

1100.1452.31002 Onze Lieve Vrouwen Gasthuis

Amsterdam, Netherlands

Location

1100.1452.34005 Boehringer Ingelheim Investigational Site

Badalona, Spain

Location

1100.1452.34001 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1100.1452.34002 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1100.1452.34004 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1100.1452.34003 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat, Spain

Location

1100.1452.34006 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1100.1452.34007 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1100.1452.34010 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1100.1452.34011 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1100.1452.34009 Boehringer Ingelheim Investigational Site

Seville, Spain

Location

1100.1452.88602 Kaohsiung Veterans General Hospital

Kaohsiung City, Taiwan

Location

1100.1452.88603 E-Da Hospital

Kaohsiung City, Taiwan

Location

1100.1452.88605 Chung-Ho Memorial Hospital, Kaohsiung Medical University

Kaohsiung City, Taiwan

Location

1100.1452.88606 China Medical University Hospital

Taichung, Taiwan

Location

1100.1452.88601 National Taiwan University Hospital

Taipei, Taiwan

Location

1100.1452.88604 Taipei City Hospital

Taipei, Taiwan

Location

1100.1452.66001 Boehringer Ingelheim Investigational Site

Bangkok, Thailand

Location

1100.1452.66002 Boehringer Ingelheim Investigational Site

Bangkok, Thailand

Location

1100.1452.66003 Boehringer Ingelheim Investigational Site

Khon Kaen, Thailand

Location

1100.1452.44006 Boehringer Ingelheim Investigational Site

Birmingham, United Kingdom

Location

1100.1452.44004 Boehringer Ingelheim Investigational Site

Brighton, United Kingdom

Location

1100.1452.44001 Boehringer Ingelheim Investigational Site

Coventry, United Kingdom

Location

1100.1452.44002 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1100.1452.44005 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1100.1452.44008 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1100.1452.44009 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1100.1452.44003 Boehringer Ingelheim Investigational Site

Manchester, United Kingdom

Location

1100.1452.44007 Boehringer Ingelheim Investigational Site

Plaistow, London, United Kingdom

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Nevirapine

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

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 28, 2006
• First Posted: April 5, 2006
• Study Start: February 1, 2006
• Primary Completion: September 1, 2008
• Last Updated: August 1, 2013

Record last verified: 2013-07

Locations

DE (13); NL (2); CA (3); AU (7); FR (33); ES (10); TW (6); GB (9); US (12); TH (3); AR (4)