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NCT00310843 Clinical Trial

Case-Control Viramune (Nevirapine) Toxicogenomics Study

HIV Infections Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data
NCT number NCT00310843
Other study ID # 1100.1452
Secondary ID 2005-004321-26
Status Completed
Phase Phase 4
First received March 28, 2006
Last updated July 31, 2013
Start date February 2006

Study information
Verified date July 2013
Source Boehringer Ingelheim
Contact n/a
Is FDA regulated No
Health authority Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Responsilble Ethics CommitteeCanada: Health Canada-Protocol Review not requiredFrance: Agence Française de Sécurité Sanitaire des Produits de SantéGermany: BfArM-Bundesinstitut fuer Arzneimittel und Medizinprodukte (Federal Authoriteis for Drugs and Medical Devices)Great Britain: MHRANetherlands: AMC (Academisch Medisch Centrum)Spain: Spanish Agency for Medicines and Health ProductsTaiwan: Department of Health, Executive Yuan, TaiwanThailand: Ministry of Public HealthUnited States: Food and Drug Administration
Study type Observational

Clinical Trial 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.

Recruitment information / eligibility
Status Completed
Enrollment 889
Est. completion date
Est. primary completion date September 2008
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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

Observational Model: Case Control, Time Perspective: Retrospective

Related Conditions & MeSH terms

Intervention

Drug:
• Nevirapine
Patients with HIV-1 infection who have taken or are currently taking nevirapine

Locations
Country Name City State
Argentina 1100.1452.54001 Fundación Huésped Capital Federal
Argentina 1100.1452.54002 Funcei Capital Federal
Argentina 1100.1452.54003 Boehringer Ingelheim Investigational Site Capital Federal
Argentina 1100.1452.54004 Boehringer Ingelheim Investigational Site Rosario
Australia 1100.1452.61002 Boehringer Ingelheim Investigational Site Carlton Victoria
Australia 1100.1452.61004 Boehringer Ingelheim Investigational Site Darlinghurst New South Wales
Australia 1100.1452.61005 Boehringer Ingelheim Investigational Site DarlingHurst New South Wales
Australia 1100.1452.61006 Boehringer Ingelheim Investigational Site Darlinghurst New South Wales
Australia 1100.1452.61008 Boehringer Ingelheim Investigational Site Melbourne Victoria
Australia 1100.1452.61003 Boehringer Ingelheim Investigational Site Miami Queensland
Australia 1100.1452.61001 Boehringer Ingelheim Investigational Site South Yarra Victoria
Canada 1100.1452.01502 Toronto General Hospital Toronto Ontario
Canada 1100.1452.01501 St. Paul's Hospital Vancouver British Columbia
Canada 1100.1452.01504 Boehringer Ingelheim Investigational Site Vancouver British Columbia
France 1100.1452.3304A Hôpital Saint André Bordeaux
France 1100.1452.3306B Hop Hôtel Dieu Lyon
France 1100.1452.3311B Pavillon P Lyon
France 1100.1452.3306A Hôpital Hôtel Dieu Lyon cedex 2
France 1100.1452.3311A Hôpital Edouard Herriot Lyon Cedex 3
France 1100.1452.3311C Hôpital Edouard Herriot Lyon cedex 3
France 1100.1452.3311D Hôpital Edouard Herriot Lyon cedex 3
France 1100.1452.3305D Hôpital Hôtel Dieu Nantes
France 1100.1452.3305F Hôpital Hôtel Dieu Nantes
France 1100.1452.3305G Hôpital Hôtel Dieu Nantes
France 1100.1452.3305I Hôpital Hôtel Dieu Nantes
France 1100.1452.3305A Hôpital hôtel Dieu Nantes cedex 1
France 1100.1452.3305B Hôpital hôtel Dieu Nantes cedex 1
France 1100.1452.3305C Hôpital hôtel Dieu Nantes cedex 1
France 1100.1452.3305E Hôpital hôtel Dieu Nantes cedex 1
France 1100.1452.3305H Hôpital hôtel Dieu Nantes cedex 1
France 1100.1452.3301A Hôpital Saint Louis Paris
France 1100.1452.3303A Hôpital de la Pité Salpêtrière Paris
France 1100.1452.3310A Hôpital Bichat Claude Bernard Paris
France 1100.1452.3310B Hôpital Bichat Claude Bernard Paris
France 1100.1452.3313B Hôpital Saint Antoine Paris
France 1100.1452.3313C Hôpital Saint Antoine Paris
France 1100.1452.3314A Hôpital Européen Georges Pompidou Paris
France 1100.1452.3313A Hôpital Saint Antoine Paris cedex 12
France 1100.1452.3302A Hôpital Tenon Paris cedex 20
France 1100.1452.3308B Hôpital Purpan Toulouse
France 1100.1452.3308A Hôpital Purpan Toulouse cedex 9
France 1100.1452.3307A Hôpital Guy Chateliez Tourcoing cedex
France 1100.1452.3307B Hôpital Guy Chateliez Tourcoing cedex
France 1100.1452.3307C Hôpital Guy Chateliez Tourcoing cedex
France 1100.1452.3307D Hôpital Guy Chateliez Tourcoing cedex
France 1100.1452.3307E Hôpital Guy Chateliez Tourcoing cedex
France 1100.1452.3312A Hôpital Brabois Vandoeuvre les Nancy
Germany 1100.1452.4901 Boehringer Ingelheim Investigational Site Berlin
Germany 1100.1452.4902 Boehringer Ingelheim Investigational Site Berlin
Germany 1100.1452.9907 Boehringer Ingelheim Investigational Site Berlin
Germany 1100.1452.4903 Boehringer Ingelheim Investigational Site Bochum
Germany 1100.1452.4918 Boehringer Ingelheim Investigational Site Bonn
Germany 1100.1452.4912 Boehringer Ingelheim Investigational Site Düsseldorf
Germany 1100.1452.4904 Boehringer Ingelheim Investigational Site Essen
Germany 1100.1452.4933 Boehringer Ingelheim Investigational Site Frankfurt am Main
Germany 1100.1452.4916 Boehringer Ingelheim Investigational Site Hamburg
Germany 1100.1452.4931 Boehringer Ingelheim Investigational Site Hamburg
Germany 1100.1452.4910 Boehringer Ingelheim Investigational Site München
Germany 1100.1452.4900 Universitätsklinikum Ulm Ulm
Germany 1100.1452.4932 Boehringer Ingelheim Investigational Site Würzburg
Netherlands 1100.1452.31001 Academisch Medisch Centrum Amsterdam
Netherlands 1100.1452.31002 Onze Lieve Vrouwen Gasthuis Amsterdam
Spain 1100.1452.34005 Boehringer Ingelheim Investigational Site Badalona
Spain 1100.1452.34001 Boehringer Ingelheim Investigational Site Barcelona
Spain 1100.1452.34002 Boehringer Ingelheim Investigational Site Barcelona
Spain 1100.1452.34004 Boehringer Ingelheim Investigational Site Barcelona
Spain 1100.1452.34003 Boehringer Ingelheim Investigational Site L'Hospitalet de Llobregat
Spain 1100.1452.34006 Boehringer Ingelheim Investigational Site Madrid
Spain 1100.1452.34007 Boehringer Ingelheim Investigational Site Madrid
Spain 1100.1452.34010 Boehringer Ingelheim Investigational Site Madrid
Spain 1100.1452.34011 Boehringer Ingelheim Investigational Site Madrid
Spain 1100.1452.34009 Boehringer Ingelheim Investigational Site Sevilla
Taiwan 1100.1452.88602 Kaohsiung Veterans General Hospital Kaohsiung
Taiwan 1100.1452.88603 E-Da Hospital Kaohsiung
Taiwan 1100.1452.88605 Chung-Ho Memorial Hospital, Kaohsiung Medical University Kaohsiung
Taiwan 1100.1452.88606 China Medical University Hospital Taichung
Taiwan 1100.1452.88601 National Taiwan University Hospital Taipei
Taiwan 1100.1452.88604 Taipei City Hospital Taipei
Thailand 1100.1452.66001 Boehringer Ingelheim Investigational Site Bangkok
Thailand 1100.1452.66002 Boehringer Ingelheim Investigational Site Bangkok
Thailand 1100.1452.66003 Boehringer Ingelheim Investigational Site Khon Kaen
United Kingdom 1100.1452.44006 Boehringer Ingelheim Investigational Site Birmingham
United Kingdom 1100.1452.44004 Boehringer Ingelheim Investigational Site Brighton
United Kingdom 1100.1452.44001 Boehringer Ingelheim Investigational Site Coventry
United Kingdom 1100.1452.44002 Boehringer Ingelheim Investigational Site London
United Kingdom 1100.1452.44005 Boehringer Ingelheim Investigational Site London
United Kingdom 1100.1452.44008 Boehringer Ingelheim Investigational Site London
United Kingdom 1100.1452.44009 Boehringer Ingelheim Investigational Site London
United Kingdom 1100.1452.44003 Boehringer Ingelheim Investigational Site Manchester
United Kingdom 1100.1452.44007 Boehringer Ingelheim Investigational Site Plaistow, London
United States 1100.1452.01003 Boehringer Ingelheim Investigational Site Baltimore Maryland
United States 1100.1452.99999 Boehringer Ingelheim Investigational Site Baltimore Connecticut
United States 1100.1452.01006 Boehringer Ingelheim Investigational Site Birmingham Alabama
United States 1100.1452.01002 Boehringer Ingelheim Investigational Site Boston Massachusetts
United States 1100.1452.01012 Boehringer Ingelheim Investigational Site Chapel hill North Carolina
United States 1100.1452.01013 Boehringer Ingelheim Investigational Site Denver Colorado
United States 1100.1452.01004 Boehringer Ingelheim Investigational Site Fort Worth Texas
United States 1100.1452.01001 Boehringer Ingelheim Investigational Site Nashville Tennessee
United States 1100.1452.01011 Boehringer Ingelheim Investigational Site New Haven Connecticut
United States 1100.1452.01016 Boehringer Ingelheim Investigational Site New York New York
United States 1100.1452.01014 Boehringer Ingelheim Investigational Site Springfield Massachusetts
United States 1100.1452.01015 Boehringer Ingelheim Investigational Site St. Louis Missouri

Sponsors (1)
Lead Sponsor Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

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

Outcome
Type Measure Description Time frame Safety issue
Primary 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 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.
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