LAUSR

AbstractIntroduction Pirfenidone film-coated tablets were developed to offer an alternative to the marketed capsule formulation. This study assessed the bioequivalence of the tablet and capsule formulations under fed and fasted states.MethodsA Phase I, open-label, randomized, four-treatment-period, four-sequence, crossover pharmacokinetics study (NCT02525484) was conducted. Each subject received an 801-mg single dose of pirfenidone as three 267-mg capsules or one 801-mg tablet under fasted and fed conditions. Pirfenidone plasma Cmax, AUC0–t and AUC0–∞ were used to assess bioequivalence.Results Forty-four subjects were randomized to treatment. The 801-mg tablet in the fasted state met bioequivalence criteria [90% confidence intervals (CI) 80.00–125.00%] for the GLSM ratios of natural log-transformed Cmax, AUC0–t and AUC0–∞. Under fed conditions, the 801-mg tablet met the bioequivalence criteria for AUC0–t and AUC0–∞, but slightly exceeded the bioequivalence criteria for the Cmax (90% CI of 108.26–125.60%). The tablet Cmax was approximately 17% higher than that of the capsules. In the fed state, the tablet Cmax, and both AUC0–t and AUC0–∞ were reduced by 39% and 17%, respectively, relative to the fasted state. The tablet and capsules had acceptable tolerability profiles.ConclusionsThe pirfenidone 801-mg tablet met bioequivalence criteria when compared with three 267-mg capsules in the fasted state. The tablet Cmax was slightly higher relative to capsules in the fed state, but this is not expected to have a clinically meaningful impact on the benefit–risk profile of pirfenidone.FundingThis work was supported by F. Hoffmann-La Roche Ltd.