Population Pharmacokinetic Analysis of Glecaprevir and Pibrentasvir in Pediatric Patients ≥ 3 to < 18 Years of Age with Genotypes 1-6 Chronic Hepatitis C Virus (HCV) Infection
Abstract
Background: Mavyret, a combination medication of glecaprevir (GLE) and pibrentasvir (PIB), is approved to treat chronic and acute hepatitis C virus (HCV) (genotypes 1-6) infection in adults and pediatric patients ≥ 3 years old. To support approval, a two-part clinical trial was conducted in adolescents (≥ 12 to < 18 years) and children (≥ 3 to < 12 years) to identify the appropriate dosage and determine the efficacy and safety in pediatric patients.
Objectives: Population pharmacokinetic (popPK) analyses reported herein aimed to (1) characterize the pharmacokinetic (PK) parameters of orally administered GLE and PIB and the sources of PK variability in pediatric patients and (2) support the use of a body weight-based pediatric GLE/PIB dose ratio of 50/20 mg in HCV-infected children.
Methods: PopPK models were built for GLE and PIB independently using nonlinear mixed-effects modeling and utilized data collected from 126 pediatric patients. Demographic, pathophysiological, and treatment factors were investigated for their impact on GLE and PIB PK.
Results: PopPK analyses of pediatric exposures confirmed comparable exposures to those of adults who achieved over 95% sustained virologic response (SVR12). The pediatric popPK model incorporated allometric body weight-based scaling and subsequently identified no covariate that significantly impacted GLE exposures. Similarly, no covariate beyond the specified allometric body weight scaling was identified to impact PIB exposures. The…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 126 participants or records.
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