A Pharmacokinetic Bioequivalence Study Comparing Pirfenidone Tablet and Capsule Dosage Forms in Healthy Adult Volunteers.

ABSTRACT

INTRODUCTION: 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. METHODS: A 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 C max, 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 C max, 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 C max (90% CI of 108.26-125.60%). The tablet C max was approximately 17% higher than that of the capsules. In the fed state, the tablet C max, 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. CONCLUSIONS: The pirfenidone 801-mg tablet met bioequivalence criteria when compared with three 267-mg capsules in the fasted state. The tablet C max 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. FUNDING: This work was supported by F. Hoffmann-La Roche Ltd.