Case-Control Viramune (Nevirapine) Toxicogenomics Study

Condition(s) targeted: HIV Infections

Intervention: DNA Blood Sampling (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Boehringer Ingelheim Pharmaceuticals

Official(s) and/or principal investigator(s):
Boehringer Ingelheim, Study Chair, Affiliation: Boehringer Ingelheim Pharmaceuticals

Overall contact:
Boehringer Ingelheim Study Coordinator, Email: clintriage@boehringer-ingelheim.com

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

Official title: A Case and Control Toxicogenomics Study to Identify Genetic Locus or Loci in Patients Who Have Experienced Symptomatic Hepatotoxicity and Severe Skin Reactions Within the First 8 Weeks of Nevirapine Therapy

Study design: Treatment, Parallel Assignment, Safety Study

Primary outcome: 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: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Boehringer Ingelheim Study Coordinator, Email: clintriage@boehringer-ingelheim.com

bUENOS AIRES, Argentina; Recruiting

BsAs, Argentina; Recruiting

Buenos Aires, Argentina; Recruiting

Boehringer Ingelheim Investigational Site, Rosario, Argentina; Recruiting

Hopital Saint Louis, Paris, France; Active, not recruiting

Hopital Tenon, Paris cedex 20, France; Recruiting

Hopital de la Pite Salpetriere, Paris, France; Recruiting

Hopital Saint Andre, Bordeaux, France; Recruiting

Hopital hotel Dieu, Nantes cedex 1, France; Recruiting

Hopital Hotel Dieu, Lyon cedex 2, France; Recruiting

Hopital Guy Chateliez, Tourcoing cedex, France; Recruiting

Hopital Purpan, Toulouse cedex 9, France; Recruiting

Hopital Bichat Claude Bernard, Paris, France; Recruiting

Hopital Edouard Herriot, Lyon Cedex 3, France; Recruiting

Hopital Brabois, Vandoeuvre les Nancy, France; Recruiting

Hopital Saint Antoine, Paris cedex 12, France; Recruiting

Hopital Europeen Georges Pompidou, Paris, France; Recruiting

Hop Hotel Dieu, Lyon, France; Recruiting

Pavillon P, Lyon, France; Recruiting

Hopital Edouard Herriot, Lyon cedex 3, France; Recruiting

Hopital Saint Antoine, Paris, France; Recruiting

Hopital Purpan, Toulouse, France; Recruiting

Hopital Hotel Dieu, Nantes, France; Recruiting

Universitatsklinikum Ulm, Ulm, Germany; Recruiting

Boehringer Ingelheim Investigational Site, Berlin, Germany; Recruiting

Boehringer Ingelheim Investigational Site, Berlin, Germany; Completed

Boehringer Ingelheim Investigational Site, Bochum, Germany; Recruiting

Boehringer Ingelheim Investigational Site, Essen, Germany; Completed

Boehringer Ingelheim Investigational Site, Munchen, Germany; Completed

Boehringer Ingelheim Investigational Site, Wurzburg, Germany; Recruiting

Boehringer Ingelheim Investigational Site, Dusseldorf, Germany; Completed

Boehringer Ingelheim Investigational Site, Hamburg, Germany; Recruiting

Boehringer Ingelheim Investigational Site, Bonn, Germany; Recruiting

Boehringer Ingelheim Investigational Site, Berlin, Germany; Not yet recruiting

Boehringer Ingelheim Investigational Site, Frankfurt am Main, Germany; Recruiting

Academisch Medisch Centrum, Amsterdam, Netherlands; Recruiting

Onze Lieve Vrouwen Gasthuis, Amsterdam, Netherlands; Recruiting

Boehringer Ingelheim Investigational Site, Barcelona, Spain; Recruiting

Boehringer Ingelheim Investigational Site, L'Hospitalet de Llobregat, Spain; Recruiting

Boehringer Ingelheim Investigational Site, Badalona, Spain; Recruiting

Boehringer Ingelheim Investigational Site, Madrid, Spain; Recruiting

Boehringer Ingelheim Investigational Site, Sevilla, Spain; Recruiting

National Taiwan University Hospital, Taipei, Taiwan; Recruiting

Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Recruiting

E-Da Hospital, Kaohsiung, Taiwan; Recruiting

Taipei Veterans General Hospital, Taipei, Taiwan; Recruiting

Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Recruiting

China Medical University Hospital, Taichung, Taiwan; Recruiting

Taichung Veterans General Hospital, Taichung, Taiwan; Recruiting

Boehringer Ingelheim Investigational Site, Bangkok, Thailand; Recruiting

Boehringer Ingelheim Investigational Site, Khon Kaen, Thailand; Recruiting

Boehringer Ingelheim Investigational Site, Coventry, United Kingdom; Recruiting

Boehringer Ingelheim Investigational Site, London, United Kingdom; Recruiting

Boehringer Ingelheim Investigational Site, Manchester, United Kingdom; Recruiting

Boehringer Ingelheim Investigational Site, Brighton, United Kingdom; Recruiting

Boehringer Ingelheim Investigational Site, Birmingham, United Kingdom; Recruiting

Boehringer Ingelheim Investigational Site, Plaistow, London, United Kingdom; Recruiting

Boehringer Ingelheim Investigational Site, Birmingham, Alabama, United States; Recruiting

St. Paul's Hospital, Vancouver, British Columbia, Canada; Recruiting

Boehringer Ingelheim Investigational Site, Vancouver, British Columbia, Canada; Recruiting

Boehringer Ingelheim Investigational Site, Denver, Colorado, United States; Recruiting

Boehringer Ingelheim Investigational Site, New Haven, Connecticut, United States; Recruiting

Boehringer Ingelheim Investigational Site, Baltimore, Connecticut, United States; Not yet recruiting

Boehringer Ingelheim Investigational Site, Baltimore, Maryland, United States; Recruiting

Boehringer Ingelheim Investigational Site, Boston, Massachusetts, United States; Recruiting

Boehringer Ingelheim Investigational Site, Springfield, Massachusetts, United States; Recruiting

Boehringer Ingelheim Investigational Site, St. Louis, Missouri, United States; Recruiting

Boehringer Ingelheim Investigational Site, DarlingHurst, New South Wales, Australia; Completed

Boehringer Ingelheim Investigational Site, Darlinghurst, New South Wales, Australia; Completed

Boehringer Ingelheim Investigational Site, Bronx, New York, United States; Recruiting

Boehringer Ingelheim Investigational Site, New York, New York, United States; Recruiting

Boehringer Ingelheim Investigational Site, Chapel hill, North Carolina, United States; Recruiting

Toronto General Hospital, Toronto, Ontario, Canada; Recruiting

Boehringer Ingelheim Investigational Site, Miami, Queensland, Australia; Completed

Boehringer Ingelheim Investigational Site, Nashville, Tennessee, United States; Recruiting

Boehringer Ingelheim Investigational Site, Fort Worth, Texas, United States; Recruiting

Boehringer Ingelheim Investigational Site, Austin, Texas, United States; Recruiting

Boehringer Ingelheim Investigational Site, Carlton, Victoria, Australia; Completed

Boehringer Ingelheim Investigational Site, SOUTH YARRA, Victoria, Australia; Completed

Boehringer Ingelheim Investigational Site, Melbourne, Victoria, Australia; Completed

Starting date: April 2006
Last updated: July 3, 2008