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

Boehringer Ingelheim102 sites in 5 countries889 target enrollmentFebruary 2006

ConditionsHIV Infections

InterventionsNevirapine

DrugsNevirapine

Overview

Phase: Not Applicable
Intervention: Nevirapine
Conditions: HIV Infections
Sponsor: Boehringer Ingelheim
Enrollment: 889
Locations: 102
Primary Endpoint: 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
Status: Completed
Last Updated: 12 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

February 2006

End Date

September 2008

Last Updated

12 years ago

Study Type

Observational

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Eligibility Criteria

Inclusion Criteria

•Inclusion for Case
•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
•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
•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.
•Exclusion for Controls
•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.

Arms & Interventions

All study population

Intervention: Nevirapine

Outcomes

Primary Outcomes

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

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.