Nonlinear Mixed Effects Modeling of Rifapentine Pharmacokinetics

Investigator: Rada Savic, PhD
Sponsor: Sanofi-Aventis Group

Location(s): Uganda


Higher doses of rifamycins demonstrate promising preclinical activity to shorten duration of tuberculosis (TB) treatment.

Two Phase 2B Trials of high dose rifapentine (RPT) were performed by Tuberculosis Trial Consortium to assess treatment duration shortening potential

PKPD analysis –Methodology, Data
PD endpoints: culture conversion results on solid and liquid media
Non-linear mixed effects modeling
   –Parametric time -to-event analysis (PKPD part)
   –Population Pharmacokinetic analysis (PK part)
Modelling Steps:
  1. Baseline model (Standard of care arm)    Data: Rifampin arm from Study 29 (73 subjects) and Study 29X (207 subjects)
  2. Drug model (comparative efficacy modelling)     Data :RPT arms (203 subjects)
 3. Covariate effect on treatment outcome
   –impact of demographics (race, age, weight, ethnicity, continent)
   –impact of disease heterogenity (HIV status, cavitary disease, recurring TB)