Case-Control Viramune (Nevirapine) Toxicogenomics Study

Completed

• Conditions: HIV Infections
• Interventions: Drug: Nevirapine

• Registration Number: NCT00310843
• Lead Sponsor: Boehringer Ingelheim

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-02
• Study First Submitted: 2006-03-28
• Study First Submitted QC: 2006-04-02
• Study First Posted: 2006-04-05
• Primary Completion: 2008-09
• Status Verified: 2013-07
• Last Update Submitted: 2013-07-31
• Last Update Posted: 2013-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 889

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
All study population	Nevirapine	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (102)

1100.1452.01006 Boehringer Ingelheim Investigational Site; 🇺🇸 Birmingham, Alabama, United States

1100.1452.01013 Boehringer Ingelheim Investigational Site; 🇺🇸 Denver, Colorado, United States

1100.1452.99999 Boehringer Ingelheim Investigational Site; 🇺🇸 Baltimore, Connecticut, United States

1100.1452.01011 Boehringer Ingelheim Investigational Site; 🇺🇸 New Haven, Connecticut, United States

1100.1452.01003 Boehringer Ingelheim Investigational Site; 🇺🇸 Baltimore, Maryland, United States

1100.1452.01002 Boehringer Ingelheim Investigational Site; 🇺🇸 Boston, Massachusetts, United States

1100.1452.01014 Boehringer Ingelheim Investigational Site; 🇺🇸 Springfield, Massachusetts, United States

1100.1452.01015 Boehringer Ingelheim Investigational Site; 🇺🇸 St. Louis, Missouri, United States

1100.1452.01016 Boehringer Ingelheim Investigational Site; 🇺🇸 New York, New York, United States

1100.1452.01012 Boehringer Ingelheim Investigational Site; 🇺🇸 Chapel hill, North Carolina, United States

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