Comparative Pharmacokinetic Study of Pirfenidone Modified-Release Tablets and Pirfenidone Tablets in Healthy Subjects Under Fed Conditions

Overview

A Randomized, Open-Label, Two-Period, Double-Crossover Comparative Study on the Pharmacokinetics of Pirfenidone Modified-Release Tablets and Pirfenidone Tablets in Healthy Chinese Subjects under Fed Conditions Primary objective: To evaluate the bioequivalence of test product and reference product by comparing their plasma concentrations and main PK parameters by oral administration in healthy Chinese subjects under fed conditions using Pirfenidone Modified-Release Tablets (strength: 600 mg/tablet) developed by Overseas Pharmaceuticals, Ltd. as the test product and Pirfenidone Tablets (trade name: Pirespa®, strength: 200 mg/tablet) produced by Shionogi \& Co., Ltd. as the reference product. Secondary objective: To evaluate the safety of Pirfenidone Modified-Release Tablets (test product) and Pirfenidone Tablets (reference product) after oral administration in healthy Chinese subjects under fed conditions.

It is designed to be a single-center, randomized, open-label, two-period, double-crossover trial. All subjects must sign an informed consent form (ICF) prior to participation in the trial. Twenty-four (24) eligible healthy subjects (male and female, with an appropriate sex ratio) screened through physical examination from D-14 to D-1 of dosing will be randomized into Group T-R and Group R-T, with 12 subjects in each group. The enrolled subjects will be admitted to phase I ward of the clinical study site 1 day before medication in each period and fasted for more than 10 h before medication. On the morning of medication, after the collection of blank blood samples within 60 minutes before administration, both group will have a standard breakfast that completed within 30 minutes. Group T will orally take 1 tablet of Pirfenidone Modified-Release Tablets (600 mg/tablet, Overseas Pharmaceuticals, Ltd.) developed by Overseas Pharmaceuticals, Ltd.in 30 minutes(±30 s) after starting a standard breakfast ; Group R will orally take 3 tablet of Pirfenidone Modified-Release Tablets (600 mg/tablet, Overseas Pharmaceuticals, Ltd.)（The first tablet should be taken 30 minutes (±30 s) after the start of a standard breakfast, the second tablet should be taken 30 minutes (±30 s) after the start of a standard lunch, and the third tablet should be taken 30 minutes (±30 s) after the start of a standard dinner）. Standard lunch is served 4 h after administration, standard dinner 10 h later, water is prohibited before and within 1 h after administration (except 240 mL water for medication), and unified diet is required during the trial. Unified diet is required during the trial. The trial method in period II is the same as that in period I, with a washout period of 6 days. PK blood sampling and blood sample processing: Cubital venous blood will be collected at 31 time points: before administration (0 h) and 0.25 h, 0.50 h, 1.00 h, 1.50 h, 2.00 h, 3.00 h, 4.00 h, 4.50 h, 5.00 h, 6.00 h, 7.00 h, 7.50 h, 8.00 h, 9.00 h, 10.00 h, 10.25 h, 10.50 h, 11.00 h, 11.50 h, 12.00 h, 12.50 h, 13.00 h, 14.00 h, 16.00 h, 18.00 h, 20.00 h, 24.00 h, 28.00 h, 36.00 h and 48.00 h after administration of each period. Four milliliters (4 mL) (scale of 4 mL should be pre-marked on the blood collection tube) will be drawn and placed in a labeled EDTA-2K anticoagulant tube. The collection, processing and storage procedures of biological samples are subject to the final sample operation manual. Sitting vital signs (including respiratory rate, body temperature, pulse rate, and sitting blood pressure) will be measured within 1 h before administration and at 2 ± 0.5 h, 8 ± 0.5 h, 24 ± 0.5 h and 48 ± 1 h after administration. Subjects should receive physical examination, vital signs, ECG, and laboratory-related tests on D2 after the last dose. The subjective feelings of subjects as well as possible adverse reactions (ARs) and adverse events (AEs) occurred during the trial should be observed and inquired. All subjects will be followed up for 7 days after the end of the last dose to inquire the occurrence of any subsequent AEs. If occurred, AEs should be recorded and followed up. An AE emerged during the trial should be followed up until it is resolved.