Clinical trial NCT00890448: Case Control Study of Pharmacogenomic Factors Associated With Hepatocellular Injury Following Exposure to Lapaquistat Acetate
Official title: A Modified Case Control Study to Identify Pharmacogenomic Factors Associated With Hepatocellular Injury Following Exposure to Lapaquistat Acetate
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Toxicity
Keywords: Alanine Transaminase elevation
Genetic Markers
DNA Markers
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-04-29
Enrollment: 66
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects who participated in lapaquistat acetate phase 2 and phase 3 clinical studies

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.

Eligibility criteria: 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:

* None

Primary outcomes:
measure: Whole genome scanning using the Illumina 1M chip.
timeFrame: Visit 2
measure: Whole genome scanning using the Affymetrix 500K array chip.
timeFrame: Visit 2
measure: Candidate gene scanning using the Affymetrix Drug Metabolizing Enzymes and Transporter (DMET) array.
timeFrame: Visit 2
Secondary outcomes:
Other outcomes:
Locations:
city: Jacksonville
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Idaho Falls
country: United States
state: Idaho
city: Richmond
country: United States
state: Virginia
city: Cordoba
country: Argentina
city: Quebec
country: Canada
city: Sainte-Foy
country: Canada
city: Santiago
country: Chile
city: Havírov-Šumbark
country: Czech Republic
city: Oulu
country: Finland
city: Nürnberg
country: Germany
city: Riga
country: Latvia
city: Groningen
country: Netherlands
city: Gdansk
country: Poland
city: Moscow
country: Russian Federation
city: Saratov
country: Russian Federation
city: Žilina
country: Slovakia
city: Johannesburg
country: South Africa
city: Glasgow
country: United Kingdom
state: Scotland
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: