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Evaluation of the Effect of Ritlecitinib on the Pharmacokinetics of Caffeine in Healthy Participants
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  • Liu Jian,
  • Rohit Solan,
  • Robert Wolk,
  • Anna Plotka,
  • Melissa O’Gorman,
  • Jennifer Winton,
  • Julia Kaplan,
  • Vivek Purohit
Liu Jian

Corresponding Author:[email protected]

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Rohit Solan
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Robert Wolk
Pfizer Inc
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Anna Plotka
Pfizer Inc
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Melissa O’Gorman
Pfizer Inc
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Jennifer Winton
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Julia Kaplan
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Vivek Purohit
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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.
20 Oct 2022Submitted to British Journal of Clinical Pharmacology
22 Oct 2022Submission Checks Completed
22 Oct 2022Assigned to Editor
22 Oct 2022Review(s) Completed, Editorial Evaluation Pending
25 Oct 2022Reviewer(s) Assigned
11 Dec 2022Editorial Decision: Revise Minor
23 Jan 20231st Revision Received
24 Jan 2023Submission Checks Completed
24 Jan 2023Assigned to Editor
24 Jan 2023Review(s) Completed, Editorial Evaluation Pending
02 Feb 2023Editorial Decision: Accept