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

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 , AUC and AUC 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 , AUC and AUC. Under fed conditions, the 801-mg tablet met the bioequivalence criteria for AUC and AUC, but slightly exceeded the bioequivalence criteria for the C (90% CI of 108.26-125.60%). The tablet C was approximately 17% higher than that of the capsules. In the fed state, the tablet C , and both AUC and AUC 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 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.