Case Control Study of Pharmacogenomic Factors Associated With Hepatocellular Injury Following Exposure to Lapaquistat Acetate

Completed

• Conditions: Toxicity
• Interventions: Other: Pharmacogenomic whole blood sampling

• Registration Number: NCT00890448
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to examine the genetic contribution to the mechanism of lapaquistat acetate- induced hepatic abnormalities.

Detailed Description

This is a modified case control study to investigate the association of genotype with phenotype in subjects who experienced alanine aminotransferase and bilirubin derangements following exposure to lapaquistat acetate.

The DNA profile of subjects who experienced significant biochemical hepatic derangement following exposure to lapaquistat acetate (cases) will be compared with a population of pre-genotyped untreated individuals (controls) from a public database. The DNA from subjects who had hepatic derangement during lapaquistat acetate studies, in the absence of exposure to lapaquistat acetate, will be stored. If data from the subjects exposed to lapaquistat acetate indicates that there is a genetic marker of interest, the stored DNA from non-exposed subjects will be assayed to further investigate the signal. One 10 mL sample of whole blood will be collected in plastic K2EDTA tube, after informed consent has been obtained.

Each subject will sign the informed consent document prior to undergoing the study-related procedure. One 10 mL sample of whole blood will be collected from each subject. Extracted DNA will be analyzed using a whole genome scan approach as well as a candidate gene approach.

Study Timeline

• Study First Submitted: 2009-04-27
• Study First Submitted QC: 2009-04-28
• Study First Posted: 2009-04-29
• Study Start: 2009-05
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Status Verified: 2012-05
• Last Update Submitted: 2012-05-23
• Last Update Posted: 2012-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

• Has experienced an alanine aminotransferase level greater than or equal to 5 times the upper limit of normal, or concurrent elevation of alanine aminotransferase greater than or equal to 3 times the upper limit of normal and bilirubin greater than or equal to 2 times the upper limit of normal while participating in lapaquistat acetate clinical studies.

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Exclusion Criteria

• None

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Lapaquistat acetate participants	Pharmacogenomic whole blood sampling	-

Primary Outcome Measures

Name	Time	Method
Whole genome scanning using the Affymetrix 500K array chip.	Visit 2
Whole genome scanning using the Illumina 1M chip.	Visit 2
Candidate gene scanning using the Affymetrix Drug Metabolizing Enzymes and Transporter (DMET) array.	Visit 2