Clinical Pharmacologist Pfizer, Inc. Groton, Connecticut, United States
Background: Abrocitinib (ABRO) is a JAK1 selective inhibitor recently approved for treating moderate-to-severe atopic dermatitis in adults and adolescents. This study aimed to estimate the relative bioavailability (rBA) of an oral suspension formulation of ABRO compared to the ABRO commercial tablet and assess the palatability of six oral suspension formulations for ABRO to guide the selection and development of ABRO pediatric formulation. Methods: In this single-dose, crossover study, 19 healthy participants were randomized to receive one of the following: ABRO 200 mg commercial tablet (TRT A) or ABRO 200 mg suspension (TRT B) for the rBA assessment. PK samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose, and PK parameters were calculated using noncompartmental methods. For palatability assessment, each participant recorded the sensory attributes at timed intervals of 0, 5, 10, and 20 minutes after swallowing each of the six suspensions, using a Taste Assessment Questionnaire. Results: Median ABRO plasma concentrations were similar when ABRO was given as TRT A compared to TRT B. The ratios of adjusted geometric means (90% CI) for the TRT B (test) and TRT A (reference) were 96.96% (85.43%, 110.03%) for AUCinf and 100.07% (80.28%, 124.74%) for Cmax. Results of the taste sensory attributes questionnaire revealed that formulations with sucralose were more favorable to study participants than those without sucralose. Conclusion: For ABRO 200 mg given as an oral suspension vs. the commercial tablet, the ratios of adjusted geometric means (90% CI) for AUCinf and Cmax were contained within the acceptance range for bioequivalence (80 - 125%). Additionally, the palatability of the different oral suspension formulations was found to be acceptable to most adult participants.
