Pharmacometrics-Based Considerations for the Design of a Pharmacogenomic Clinical Trial Assessing Irinotecan Safety.

ABSTRACT:

Purpose

Pharmacometric models provide useful tools to aid the rational design of clinical trials. This study evaluates study design-, drug-, and patient-related features as well as analysis methods for their influence on the power to demonstrate a benefit of pharmacogenomics (PGx)-based dosing regarding myelotoxicity.

Methods

Two pharmacokinetic and one myelosuppression model were assembled to predict concentrations of irinotecan and its metabolite SN-38 given different UGT1A1 genotypes (poor metabolizers: CL_SN-38: -36%) and neutropenia following conventional versus PGx-based dosing (350 versus 245 mg/m² (-30%)). Study power was assessed given diverse scenarios (n = 50-400 patients/arm, parallel/crossover, varying magnitude of CL_SN-38, exposu

SUBMITTER: Minichmayr IK 

PROVIDER: S-EPMC8057977 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature