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Case-Control Viramune (Nevirapine) Toxicogenomics Study

Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT00310843
Collaborator
(none)
889
Enrollment
102
Locations
8.7
Patients Per Site

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase

Study Design

Study Type:
Observational
Actual Enrollment :
889 participants
Observational Model:
Case-Control
Time Perspective:
Retrospective
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
Study Start Date :
Feb 1, 2006
Actual Primary Completion Date :
Sep 1, 2008

Arms and Interventions

Arm Intervention/Treatment
All study population

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

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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. []

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  1. 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

  1. Patients who discontinued nevirapine before completing 18 weeks of dosing with 200 mg/day for 2 weeks followed by 400 mg/day thereafter.

  2. 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.

  3. Patients with ALT or AST elevations >2.5 X ULN (>Grade 1) within 18 weeks of starting nevirapine therapy.

  4. Any hepatobiliary adverse event that could possibly be attributed to nevirapine.

  5. 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

  1. Patients who have participated in the 2NN-Long-term Follow-up study (1100.1454)

  2. 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).

  3. Evidence of acute co-infection with viral hepatitis.

  4. Patients taking prednisone, prednisolone, or immuno-modulatory medication within the first 8 weeks of nevirapine therapy.

  5. Patients who are unwilling to provide blood samples for DNA testing.

  6. Patients who did not sign informed consent and or authorization to release protected health information per local requirements.

  7. Patients without available liv

Contacts and Locations

Locations

Site City State Country Postal Code
1 1100.1452.01006 Boehringer Ingelheim Investigational Site Birmingham Alabama United States
2 1100.1452.01013 Boehringer Ingelheim Investigational Site Denver Colorado United States
3 1100.1452.99999 Boehringer Ingelheim Investigational Site Baltimore Connecticut United States
4 1100.1452.01011 Boehringer Ingelheim Investigational Site New Haven Connecticut United States
5 1100.1452.01003 Boehringer Ingelheim Investigational Site Baltimore Maryland United States
6 1100.1452.01002 Boehringer Ingelheim Investigational Site Boston Massachusetts United States
7 1100.1452.01014 Boehringer Ingelheim Investigational Site Springfield Massachusetts United States
8 1100.1452.01015 Boehringer Ingelheim Investigational Site St. Louis Missouri United States
9 1100.1452.01016 Boehringer Ingelheim Investigational Site New York New York United States
10 1100.1452.01012 Boehringer Ingelheim Investigational Site Chapel hill North Carolina United States
11 1100.1452.01001 Boehringer Ingelheim Investigational Site Nashville Tennessee United States
12 1100.1452.01004 Boehringer Ingelheim Investigational Site Fort Worth Texas United States
13 1100.1452.54001 Fundación Huésped Capital Federal Argentina
14 1100.1452.54002 Funcei Capital Federal Argentina
15 1100.1452.54003 Boehringer Ingelheim Investigational Site Capital Federal Argentina
16 1100.1452.54004 Boehringer Ingelheim Investigational Site Rosario Argentina
17 1100.1452.61004 Boehringer Ingelheim Investigational Site Darlinghurst New South Wales Australia
18 1100.1452.61005 Boehringer Ingelheim Investigational Site DarlingHurst New South Wales Australia
19 1100.1452.61006 Boehringer Ingelheim Investigational Site Darlinghurst New South Wales Australia
20 1100.1452.61003 Boehringer Ingelheim Investigational Site Miami Queensland Australia
21 1100.1452.61002 Boehringer Ingelheim Investigational Site Carlton Victoria Australia
22 1100.1452.61008 Boehringer Ingelheim Investigational Site Melbourne Victoria Australia
23 1100.1452.61001 Boehringer Ingelheim Investigational Site South Yarra Victoria Australia
24 1100.1452.01501 St. Paul's Hospital Vancouver British Columbia Canada
25 1100.1452.01504 Boehringer Ingelheim Investigational Site Vancouver British Columbia Canada
26 1100.1452.01502 Toronto General Hospital Toronto Ontario Canada
27 1100.1452.3304A Hôpital Saint André Bordeaux France
28 1100.1452.3306A Hôpital Hôtel Dieu Lyon cedex 2 France
29 1100.1452.3311A Hôpital Edouard Herriot Lyon Cedex 3 France
30 1100.1452.3311C Hôpital Edouard Herriot Lyon cedex 3 France
31 1100.1452.3311D Hôpital Edouard Herriot Lyon cedex 3 France
32 1100.1452.3306B Hop Hôtel Dieu Lyon France
33 1100.1452.3311B Pavillon P Lyon France
34 1100.1452.3305A Hôpital hôtel Dieu Nantes cedex 1 France
35 1100.1452.3305B Hôpital hôtel Dieu Nantes cedex 1 France
36 1100.1452.3305C Hôpital hôtel Dieu Nantes cedex 1 France
37 1100.1452.3305E Hôpital hôtel Dieu Nantes cedex 1 France
38 1100.1452.3305H Hôpital hôtel Dieu Nantes cedex 1 France
39 1100.1452.3305D Hôpital Hôtel Dieu Nantes France
40 1100.1452.3305F Hôpital Hôtel Dieu Nantes France
41 1100.1452.3305G Hôpital Hôtel Dieu Nantes France
42 1100.1452.3305I Hôpital Hôtel Dieu Nantes France
43 1100.1452.3313A Hôpital Saint Antoine Paris cedex 12 France
44 1100.1452.3302A Hôpital Tenon Paris cedex 20 France
45 1100.1452.3301A Hôpital Saint Louis Paris France
46 1100.1452.3303A Hôpital de la Pité Salpêtrière Paris France
47 1100.1452.3310A Hôpital Bichat Claude Bernard Paris France
48 1100.1452.3310B Hôpital Bichat Claude Bernard Paris France
49 1100.1452.3313B Hôpital Saint Antoine Paris France
50 1100.1452.3313C Hôpital Saint Antoine Paris France
51 1100.1452.3314A Hôpital Européen Georges Pompidou Paris France
52 1100.1452.3308A Hôpital Purpan Toulouse cedex 9 France
53 1100.1452.3308B Hôpital Purpan Toulouse France
54 1100.1452.3307A Hôpital Guy Chateliez Tourcoing cedex France
55 1100.1452.3307B Hôpital Guy Chateliez Tourcoing cedex France
56 1100.1452.3307C Hôpital Guy Chateliez Tourcoing cedex France
57 1100.1452.3307D Hôpital Guy Chateliez Tourcoing cedex France
58 1100.1452.3307E Hôpital Guy Chateliez Tourcoing cedex France
59 1100.1452.3312A Hôpital Brabois Vandoeuvre les Nancy France
60 1100.1452.4901 Boehringer Ingelheim Investigational Site Berlin Germany
61 1100.1452.4902 Boehringer Ingelheim Investigational Site Berlin Germany
62 1100.1452.9907 Boehringer Ingelheim Investigational Site Berlin Germany
63 1100.1452.4903 Boehringer Ingelheim Investigational Site Bochum Germany
64 1100.1452.4918 Boehringer Ingelheim Investigational Site Bonn Germany
65 1100.1452.4912 Boehringer Ingelheim Investigational Site Düsseldorf Germany
66 1100.1452.4904 Boehringer Ingelheim Investigational Site Essen Germany
67 1100.1452.4933 Boehringer Ingelheim Investigational Site Frankfurt am Main Germany
68 1100.1452.4916 Boehringer Ingelheim Investigational Site Hamburg Germany
69 1100.1452.4931 Boehringer Ingelheim Investigational Site Hamburg Germany
70 1100.1452.4910 Boehringer Ingelheim Investigational Site München Germany
71 1100.1452.4900 Universitätsklinikum Ulm Ulm Germany
72 1100.1452.4932 Boehringer Ingelheim Investigational Site Würzburg Germany
73 1100.1452.31001 Academisch Medisch Centrum Amsterdam Netherlands
74 1100.1452.31002 Onze Lieve Vrouwen Gasthuis Amsterdam Netherlands
75 1100.1452.34005 Boehringer Ingelheim Investigational Site Badalona Spain
76 1100.1452.34001 Boehringer Ingelheim Investigational Site Barcelona Spain
77 1100.1452.34002 Boehringer Ingelheim Investigational Site Barcelona Spain
78 1100.1452.34004 Boehringer Ingelheim Investigational Site Barcelona Spain
79 1100.1452.34003 Boehringer Ingelheim Investigational Site L'Hospitalet de Llobregat Spain
80 1100.1452.34006 Boehringer Ingelheim Investigational Site Madrid Spain
81 1100.1452.34007 Boehringer Ingelheim Investigational Site Madrid Spain
82 1100.1452.34010 Boehringer Ingelheim Investigational Site Madrid Spain
83 1100.1452.34011 Boehringer Ingelheim Investigational Site Madrid Spain
84 1100.1452.34009 Boehringer Ingelheim Investigational Site Sevilla Spain
85 1100.1452.88602 Kaohsiung Veterans General Hospital Kaohsiung Taiwan
86 1100.1452.88603 E-Da Hospital Kaohsiung Taiwan
87 1100.1452.88605 Chung-Ho Memorial Hospital, Kaohsiung Medical University Kaohsiung Taiwan
88 1100.1452.88606 China Medical University Hospital Taichung Taiwan
89 1100.1452.88601 National Taiwan University Hospital Taipei Taiwan
90 1100.1452.88604 Taipei City Hospital Taipei Taiwan
91 1100.1452.66001 Boehringer Ingelheim Investigational Site Bangkok Thailand
92 1100.1452.66002 Boehringer Ingelheim Investigational Site Bangkok Thailand
93 1100.1452.66003 Boehringer Ingelheim Investigational Site Khon Kaen Thailand
94 1100.1452.44006 Boehringer Ingelheim Investigational Site Birmingham United Kingdom
95 1100.1452.44004 Boehringer Ingelheim Investigational Site Brighton United Kingdom
96 1100.1452.44001 Boehringer Ingelheim Investigational Site Coventry United Kingdom
97 1100.1452.44002 Boehringer Ingelheim Investigational Site London United Kingdom
98 1100.1452.44005 Boehringer Ingelheim Investigational Site London United Kingdom
99 1100.1452.44008 Boehringer Ingelheim Investigational Site London United Kingdom
100 1100.1452.44009 Boehringer Ingelheim Investigational Site London United Kingdom
101 1100.1452.44003 Boehringer Ingelheim Investigational Site Manchester United Kingdom
102 1100.1452.44007 Boehringer Ingelheim Investigational Site Plaistow, London United Kingdom

Sponsors and Collaborators

  • Boehringer Ingelheim

Investigators

  • Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
, ,
ClinicalTrials.gov Identifier:
NCT00310843
Other Study ID Numbers:
  • 1100.1452
  • 2005-004321-26
First Posted:
Apr 5, 2006
Last Update Posted:
Aug 1, 2013
Last Verified:
Jul 1, 2013
Additional relevant MeSH terms:
HIV Infections
Nevirapine

Study Results

No Results Posted as of Aug 1, 2013