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

Toxicity Clinical Trial

Official title:

A Modified Case Control Study to Identify Pharmacogenomic Factors Associated With Hepatocellular Injury Following Exposure to Lapaquistat Acetate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00890448
• Other study ID #: TAK-475_310
• Secondary ID: 2008-006906-41U1
• Status: Completed
• Phase: N/A
• First received: April 27, 2009
• Last updated: May 23, 2012
• Start date: May 2009
• Est. completion date: May 2010

Study information

• Verified date: May 2012
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Exclusion Criteria:

Study Design

Observational Model: Case Control

Related Conditions & MeSH terms

• Toxicity

Intervention

Other:
• Pharmacogenomic whole blood sampling
10 mL, whole blood, one sample on Visit 2

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  Czech Republic,  Finland,  Germany,  Latvia,  Netherlands,  Poland,  Russian Federation,  Slovakia,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Whole genome scanning using the Illumina 1M chip.		Visit 2	No
Primary	Whole genome scanning using the Affymetrix 500K array chip.		Visit 2	No
Primary	Candidate gene scanning using the Affymetrix Drug Metabolizing Enzymes and Transporter (DMET) array.		Visit 2	No