Case-Control Viramune (Nevirapine) Toxicogenomics Study
This study has been completed.
Information provided by:
Boehringer Ingelheim Pharmaceuticals
First received: March 28, 2006
Last updated: May 18, 2012
Last verified: May 2012
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.
Procedure: DNA Blood Sampling
||Intervention Model: Parallel Assignment
Primary Purpose: Treatment
||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
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.
| Study Start Date:
| Primary Completion Date:
||September 2008 (Final data collection date for primary outcome measure)
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
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 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.
Exclusion for Cases and Controls
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00310843
Boehringer Ingelheim Pharmaceuticals
||Boehringer Ingelheim Pharmaceuticals
No publications provided
||Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
History of Changes
|Other Study ID Numbers:
|Study First Received:
||March 28, 2006
||May 18, 2012
||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:
ClinicalTrials.gov processed this record on May 19, 2013
Acquired Immunodeficiency Syndrome
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Molecular Mechanisms of Pharmacological Action