Genentech Inc., 1 DNA way, South San Francisco, CA, 94080-4990, USA.
Published: September 2017
AI Article Synopsis
Article 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 , 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.
Background: The benefit of sildenafil in patients with advanced idiopathic pulmonary fibrosis (IPF) at risk of poor outcomes from pulmonary hypertension, whether already present or likely to develop, is uncertain. We aimed to assess the efficacy and safety of sildenafil added to pirfenidone versus placebo added to pirfenidone for 52 weeks in patients with advanced IPF and at risk of group 3 pulmonary hypertension.
Methods: We did a multicentre, international, double-blind, randomised, placebo-controlled, phase 2b study at 56 university clinics, research hospitals, and tertiary sites in Canada, Europe (Belgium, Czech Republic, Germany, Greece, Hungary, Italy, the Netherlands, Spain, and Turkey), Israel, and Africa (Egypt and South Africa).
Department of Respiratory Medicine, National Coordinating Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France.
Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating interstitial lung disease. Two antifibrotics, pirfenidone and nintedanib, are available for IPF treatment. Pirfenidone is available as 267 mg capsules and, more recently, as 267 mg and 801 mg tablets.
Pirfenidone (Esbriet) is available as capsules containing 267 mg of pirfenidone and, more recently, as bioequivalent tablets containing 267, 534 or 801 mg of pirfenidone. Both formulations are indicated to treat idiopathic pulmonary fibrosis (IPF), with pirfenidone being shown to generally reduce the rate of decline in forced vital capacity in patients with mild to moderate IPF, while prolonging progression-free survival and reducing the risk of IPF-related and all-cause mortality. The availability of the tablet formulation reduces the daily pill burden of pirfenidone, as the recommended daily divided maintenance dose of 2403 mg/day may be administered as one 801 mg tablet three times daily instead of three 267 mg capsules three times daily.
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.
