PGx7610: Genetic Evaluation of Hepatotoxicity in Pazopanib Studies (201761)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Other
• If ‘other’, further details on the scope of the study:
  Pharmacogenetics study
• Data collection methods:
  Secondary data collection

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Pharmacogenetics study

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  PAZOPANIB

Population studied

• Short description of the study population:
  Patients enrolled in any of the 23 clinical studies, who were exposed to at least one dose of pazopanib and gave a sample for genetic analyses.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  1080

Study design details

• Main study objective:
  To evaluate genetic associations between HLA-B*57:01 and ALT elevationin pazopanib-treated subjects from 23 clinical studies
• Outcomes:
  Evaluate carriage of a single haplotype (HLA-B*57:01) in all pazopanibtreated subjects from 23 clinical trials for maximum on-treatment ALT using a one-tailed test, Test association between carriage of the HLA-B*57:01 allele, andsecondary measures of ALT elevation, in patients treated with pazopanib, and test association between genotypes at 16 pre-specified SNPs, and ALTelevation, in patients treated with pazopanib.
• Data analysis plan:
  The primary analysis will evaluate carriage of a single allele (HLA-B*57:01) for a single endpoint using a one-tailed test, and will have controlled false positive rate 5%.Secondary analyses of association between HLA-B*57:01 and other endpoints will be for effect size estimation and for exploratory purposes. Significant association with a secondary endpoint, but not with the primary endpoint, would not be considered a strict sense replication of the association observed in the exploratory analysis.For secondary analyses of the 16 SNPs, false positives will be controlled at 5% for the primary endpoint (maximum on-treatment ALT), using a Bonferroni correction for 16 tests. Secondary analyses for these SNPs with other endpoints will be for effect size estimation and for exploratory purposes.

Documents

Study results

gsk-201761-clinical-study-report-redact