Case-Control Viramune (Nevirapine) Toxicogenomics Study

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00310843
• Date of registration: 28/03/2006
• Prospective Registration: No
• Primary sponsor: Boehringer Ingelheim
• Public title: Case-Control Viramune (Nevirapine) Toxicogenomics Study
• Scientific 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
• Date of first enrolment: February 2006
• Target sample size: 889
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00310843
• Study type: Observational
• Study design: Observational Model: Case Control, Time Perspective: Retrospective

Countries of recruitment

Argentina, Australia, Canada, France, Germany, Netherlands, Spain, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: Boehringer Ingelheim
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

HIV Infections

Intervention(s)

Drug: Nevirapine

Primary Outcome(s)

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(s)

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.

Secondary ID(s)

1100.1452

2005-004321-26

Source(s) of Monetary Support

Please refer to primary and secondary sponsors