Leveraging Prior Healthy Participant Pharmacokinetic Data to Evaluate the Impact of Renal and Hepatic Impairment on Ritlecitinib Pharmacokinetics

We present results from each study and two innovative approaches to utilizing available HP data as reference data for study 2: a statistical approach using analysis of variance and anin silico simulation of an HP cohort created using a population pharmacokinetics (POPPK) model derived from several ritlecitinib studies. For study 1, the observed area under the curve for 24-h  dosing interval and maximum plasma concentration for HPs and their observed geometric mean ratios (participants with moderate hepatic impairmentvs HPs) were within 90% prediction intervals from the POPPK simulation-based approach, thereby validating the latter approach. When applied to study 2, both the statistical and POPPK simulation approaches demonstrated that  patients with renal impairment would not require ritlecitinib dose modification. In both phase I studies, ritlecitinib was generally safe and well tolerated. These analyses represent a new methodology for generating reference HP cohorts in special population studies for drugs in development with w ell-characterized pharmacokinetics in HPs and adequate POPPK models.Trial RegistrationClinicalTrials.govNCT04037865,NCT04016077,NCT02309827,NCT02684760, andNCT02969044.Graphical Abstract
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research