Avacopan 30 mg twice daily (BID) is approved for the treatment of severe active antineutrophil cytoplasmic autoantibody-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis). Food effect on avacopan pharmacokinetics (PKs) and PK bridging in Japanese participants were examined through 2 phase 1 studies involving healthy adult participants. In Study 1, an open-label, crossover trial, participants received oral administration of a single 30-mg dose of avacopan under fasted and fed conditions. Study 2 was a randomized, single-blind, placebo-controlled trial in Caucasian and Japanese participants: Part A investigated single doses of 10 and 30 mg of avacopan under fasted and fed conditions and Part B investigated 30 and 50 mg BID avacopan. The PKs of single-dose administrations of 10 and 30 mg in Japanese participants was compared with that in Caucasian participants under fasted conditions. Food substantially increased plasma avacopan area under the plasma concentration-time curve from time 0 to time infinity (AUC0-inf) by 1.72-fold, supporting the recommendation of taking avacopan with food. Maximum plasma concentration (Cmax) remained relatively unchanged. The median time to reach Cmax (tmax) was delayed by 3 hours. No significant food effect was observed on the active metabolite CCX168-M1 (M1) AUC. Avacopan and M1 exposures were <1.5-fold higher in Japanese participants than in Caucasian participants following multiple-dose administration of avacopan.
Keywords: Japanese; avacopan; bridging; food effect; pharmacokinetics.
© 2024, The American College of Clinical Pharmacology.