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

Overview

A Randomized, Open-Label, Single-Dose, Double-period, Double-Crossover Comparative Study on the Pharmacokinetics of Pirfenidone Modified-Release Tablets by Oral Administration in Healthy Chinese Subjects Under Fasting and Fed Conditions. Primary objective: To evaluate the food effect on test product by comparing their plasma concentrations and main Pharmacokinetics (PK) parameters by oral administration of test product in healthy Chinese subjects under fasting and fed conditions using Pirfenidone Modified-Release Tablets (strength: 600 mg/tablet) developed by Overseas Pharmaceuticals, Ltd. as the test product. Secondary objective: To evaluate the safety of Pirfenidone Modified-Release Tablets (test product) by oral administration in healthy Chinese subjects under fasting and 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. Eightteen (18) eligible healthy subjects (male and female, with an appropriate sex ratio) screened through physical examination from Day-14 (D-14) to D-1 of dosing will be randomized into Group A-B and Group B-A, with 9 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, Group A will orally take 1 tablet of Pirfenidone Modified-Release Tablets (600 mg/tablet, Overseas Pharmaceuticals, Ltd.) developed by Overseas Pharmaceuticals, Ltd. under fasting conditions; Group B will orally take 1 tablet of Pirfenidone Modified-Release Tablets (600 mg/tablet, Overseas Pharmaceuticals, Ltd.) under high-fat, high-calorie meals. Group A (fasting): After fasting for at least 10 h overnight, about 4 mL of blank blood was collected within 60 minutes before administration on the morning of administration, and then 600 mg of the test drug was taken orally on fasting condition with 240 mL of warm water. Group B (fed): After fasting for at least 10 h on the night, about 4 mL of blank blood was collected within 60 min before administration on the morning of administration. Then group B start to eat high-fat and high-heat breakfast, and meals are stopped at 10 min±30 s. 600 mg of the test product was orally administered with 240 mL warm water within 12 min after starting to eat. After taking the product, group B continue to eat high-fat and high-heat breakfast, and the total meal time should be controlled within 30 minutes . No food is allowed to be taken within 4 h after medication. 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, electrocardiograms (ECGs), 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.