Fevipiprant (QAW039) demonstrates safety, tolerability and consistent PK at high oral doses

Abstract

Introduction: Fevipiprant, an oral prostaglandin D2 receptor 2 (DP2/CRTh2) antagonist, is in clinical development for treatment of allergic conditions. We assessed safety, tolerability and pharmacokinetics (PK) after high single and multiple doses of fevipiprant in healthy subjects. Methods: In this Phase I double-blind, placebo-controlled study with 3 cohorts, 29 non-Japanese subjects were randomised 2:1 in Cohorts A, AA (repeat of Cohort A) and C to receive a single oral dose followed by safety review and multiple once-daily oral doses for 7 days. Cohorts A and AA received fevipiprant 900mg or matching placebo and Cohort C fevipiprant 1800mg or matching placebo. Cohort B (n=9 Japanese subjects) received a single dose of fevipiprant 900mg or placebo. Safety and PK of fevipiprant were assessed. Results: The number of AEs was comparable between treatment groups; tachycardia of moderate severity was seen in 1 subject on fevipiprant 900mg without additional symptoms. This event led to temporary halt of study and repeat of Cohort A after protocol amendment. No AEs were seen in Japanese subjects. No SAEs, deaths, or clinically relevant changes in ECG, laboratory values or vital signs (except tachycardia) occurred. Systemic exposure to fevipiprant and its metabolite increased by 2-fold with increase in dose from 900mg to 1800mg. Steady state was reached in 4 days with on average 1.4-fold accumulation of fevipiprant. No ethnic differences between Japanese and non-Japanese subjects were seen. Conclusion: Fevipiprant was safe and well tolerated at single and multiple oral doses up to 4-fold higher than the highest dose in the ongoing Phase III program and an increased exposure with dose up to 1800mg was seen.