To examine the genetic contribution to the mechanism of lapaquistat acetate induced hepatic abnormalities.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Whole genome scanning using the Illumina 1M chip. The Illumina 1M chip can
measure about 1,000,000 single-nucleotide polymorphisms (SNPs) and 14,000 copy
number variation regions.
• Whole genome scanning using the Affymetrix 500K array chip. The Affymetrix
500K array can measure about 500,000 SNPs.
• Candidate gene scanning using the Affymetrix Drug Metabolizing Enzymes and
Transporter (DMET) array. The Affymetrix DMETTM Plus chip can measure 1936 drug
disposition markers in 225 genes that have been associated with drug
absorption, distribution, metabolism, and excretion.
Secondary outcome
NVT
Background summary
Protocol page 22
Study objective
To examine the genetic contribution to the mechanism of lapaquistat acetate
induced hepatic abnormalities.
Study design
This is a modified case control study to identify pharmacogenomic factors
associated with hepatocellular injury following exposure to lapaquistat acetate.
The DNA profile of subjects that experienced significant biochemical hepatic
derangement following exposure to lapaquistat acetate will be compared with the
DNA profiles of a population of pregenotyped untreated control subjects from a
public database to investigate the association of hepatocellular injury with
genetic polymorphism. 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.
Each subject will sign the informed consent document prior to undergoing the
study-related procedure. One 10 mL samle 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 burden and risks
NVT
E19 Business Park, Battelsesteenweg 455B
2800 Mechelen
België
E19 Business Park, Battelsesteenweg 455B
2800 Mechelen
België
Listed location countries
Age
Inclusion criteria
Subjects that experienced marked ALT increases (>=5×ULN or concurrent elevation of ALT >=3×ULN and bilirubin >=2×ULN) during the original lapaquistat acetate development program.
Exclusion criteria
Not applicable.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-006906-41-NL |
| CCMO | NL27672.003.09 |