A Phase I, Open-Label, Randomized, Four-Treatment Period, Four-Sequence, Single-Dose, Crossover, Pharmacokinetic Bioequivalence Study Comparing Pirfenidone Tablet and Capsule Dosage Forms in Healthy Adult Volunteers
Overview
- Phase
- Phase 1
- Intervention
- Pirfenidone
- Conditions
- Healthy Volunteer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 44
- Primary Endpoint
- AUC from Time Zero to Infinity (AUC[0-inf]) of Pirfenidone
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This is a Phase I, open-label, randomized, four-treatment period, four-sequence, single-dose, crossover pharmacokinetic study to determine the bioequivalence of pirfenidone after administration of tablet and capsule dosage forms under both fed and fasted conditions.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants between 18 and 55 years of age, inclusive, at the time of screening
- •Participants of body mass index of 18.5-30.0 kilograms per square meter (kg/m\^2), inclusive
- •Participants of reproductive potential must be willing to use reliable contraceptive methods
Exclusion Criteria
- •Participants with significant medical history or unstable hepatic, pulmonary, metabolic, neurologic, cardiovascular, gastrointestinal, hematologic, or psychiatric systems, in the opinion of the investigator that may alter the absorption, metabolism, or elimination of study drug
- •Participants with calculated creatinine clearance rate less than (\<) 30 milliliters per minute (mL/min) (calculated using the Cockcroft-Gault equation) at screening
- •Participants with any use of, or intent to use, medications, including prescription, over-the-counter, herbal preparations, or vitamin/mineral supplementation other than study medications from 14 days before screening through the follow-up telephone call (except for contraception purpose)
- •Participants who have received fluvoxamine therapy within 28 days before screening
- •Participants who have received any medications known to chronically alter drug absorption, metabolism, or elimination processes within 28 days of screening, or participants who are taking drugs known to affect liver function, in the opinion of the Sponsor or investigator
- •Participants who have taken investigative drug and/or device in another clinical study within 28 days or within the investigational drug 5 half-lives, whichever is longer, before screening
- •Participants previously dosed in any pirfenidone clinical study
- •Participants with any hypersensitivity or idiosyncratic reaction to pirfenidone or the constituents of pirfenidone
- •Participants with any elevation of liver test results (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma-glutamyl transferase \[GGT\], direct bilirubin, or alkaline phosphatase above the upper limit of normal)
- •Participants with the following hemoglobin levels at screening: males \< 13.5 grams per deciliter (g/dL), females \< 11.5 g/dL
Arms & Interventions
Pirfenidone ACBD treatment sequence
Participants will be given 801 milligrams (mg) single oral doses of pirfenidone on Days 1, 4, 7 and 10 during the study. Participants will be administered, capsules (3 x 267-mg capsule) in fed state (treatment A) on Day 1 and in fasted state (treatment C) on Day 4, 801-mg tablet in fed state (treatment B) on Day 7 and in fasted state (treatment D) on Day 10.
Intervention: Pirfenidone
Pirfenidone BADC treatment sequence
Participants will be given 801 mg single oral doses of pirfenidone on Days 1, 4, 7 and 10 during the study. Participants will be administered, 801-mg tablet in fed state (treatment B) on Day 1, capsules (3 x 267-mg capsule) in fed state (treatment A) on Day 4, 801-mg tablet in fasted state (treatment D) on Day 7 and capsules (3 x 267-mg capsule) in fasted state (treatment C) on Day 10.
Intervention: Pirfenidone
Pirfenidone CDAB treatment sequence
Participants will be given 801 mg single oral doses of pirfenidone on Days 1, 4, 7 and 10 during the study. Participants will be administered, capsules (3 x 267-mg capsule) in fasted state (treatment C) on Day 1, 801-mg tablet in fasted state (treatment D) on Day 4, capsules (3 x 267-mg capsule) in fed state (treatment A) on Day 7 and 801-mg tablet in fed state (treatment B) on Day 10.
Intervention: Pirfenidone
Pirfenidone DBCA treatment sequence
Participants will be given 801 mg single oral doses of pirfenidone on Days 1, 4, 7 and 10 during the study. Participants will be administered, 801-mg tablet in fasted state (treatment D) on Day 1 and in fed state (treatment C) on Day 4, capsules (3 x 267-mg capsule) in fasted state (treatment C) on Day 7 and in fed state (treatment A) on Day 10.
Intervention: Pirfenidone
Outcomes
Primary Outcomes
AUC from Time Zero to Infinity (AUC[0-inf]) of Pirfenidone
Time Frame: 11 days
Peak Plasma Concentration (Cmax) of Pirfenidone
Time Frame: 11 days
Area Under the Plasma Concentration Versus Time Curve (AUC) from Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of Pirfenidone
Time Frame: 11 days
Secondary Outcomes
- Ratio of AUC(0-t) to AUC(0-inf) of Pirfenidone(11 days)
- Terminal Elimination Rate Constant of Pirfenidone(11 days)
- Apparent Terminal Half-Life (t1/2) of Pirfenidone(11 days)
- Time to Peak Plasma Concentration of Pirfenidone(11 days)