Evaluation of the Effect of Ritlecitinib on the Pharmacokinetics of
Caffeine in Healthy Participants
Abstract
Objective: This clinical study was conducted to evaluate the impact of
ritlecitinib on the pharmacokinetics (PK) of caffeine, a cytochrome P450
1A2 (CYP1A2) substrate. Methods: In this single-center, single-arm,
open-label, fixed-sequence study, healthy participants received a single
100-mg dose of caffeine on two separate occasions: on Day 1 of Period 1
as monotherapy and on Day 8 of Period 2 after oral administration of
ritlecitinib 200 mg once daily (QD) for 8 days. Serial blood samples
were collected and analyzed using a validated LC/MS assay. PK parameters
were estimated by using a non-compartmental method. Safety was monitored
by physical examination, vital signs, electrocardiograms, and laboratory
assessments. Results: Twelve participants were enrolled and completed
the study. Co-administration of caffeine 100 mg in the presence of
steady-state levels of ritlecitinib (200 mg QD) increased caffeine
exposure compared with caffeine given alone. Area under the curve
(AUCinf) and maximum concentration (Cmax) of caffeine increased by
approximately 165% and 10%, respectively, when co-administered with
ritlecitinib. The ratios of the adjusted geometric means (90% CI) for
caffeine AUCinf and Cmax were 265.14% (234.12%-300.26%) and 109.74%
(103.90%-15.91%), respectively, when caffeine was co-administered with
steady-state ritlecitinib (test) compared with its administration alone
(reference). Multiple doses of ritlecitinib when co-administered with a
single dose of caffeine were generally safe and well tolerated in
healthy participants. Conclusion: Ritlecitinib is a moderate inhibitor
of CYP1A2 and can increase systemic exposures of CYP1A2 substrates.