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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00890448
First received: April 27, 2009
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention
Toxicity
Other: Pharmacogenomic whole blood sampling

Study Type: Observational
Study Design: Observational Model: Case Control
Official Title: A Modified Case Control Study to Identify Pharmacogenomic Factors Associated With Hepatocellular Injury Following Exposure to Lapaquistat Acetate

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Whole genome scanning using the Illumina 1M chip. [ Time Frame: Visit 2 ] [ Designated as safety issue: No ]
  • Whole genome scanning using the Affymetrix 500K array chip. [ Time Frame: Visit 2 ] [ Designated as safety issue: No ]
  • Candidate gene scanning using the Affymetrix Drug Metabolizing Enzymes and Transporter (DMET) array. [ Time Frame: Visit 2 ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Pharmacogenomic whole blood sample


Estimated Enrollment: 66
Study Start Date: May 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Lapaquistat acetate participants Other: Pharmacogenomic whole blood sampling
10 mL, whole blood, one sample on Visit 2
Other Name: TAK-475

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects who participated in lapaquistat acetate phase 2 and phase 3 clinical studies

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00890448

  Show 19 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00890448     History of Changes
Other Study ID Numbers: TAK-475_310, 2008-006906-41, U1111-1112-3768, DOH-27-0410-2857
Study First Received: April 27, 2009
Last Updated: May 23, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Takeda:
Alanine Transaminase elevation
Genetic Markers
DNA Markers

Additional relevant MeSH terms:
Liver Diseases
Wounds and Injuries
Digestive System Diseases

ClinicalTrials.gov processed this record on April 17, 2014