Three-Arm Study of the Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis

A Randomized, Double-Blind, Placebo Controlled, Phase 3, Three-Arm Study of the Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis

The objectives of this study are to assess the safety and efficacy of treatment with pirfenidone 2403 milligrams per day (mg/d) compared with placebo in patients with idiopathic pulmonary fibrosis (IPF), to assess the safety and efficacy of treatment with pirfenidone 1197 mg/d in patients with idiopathic pulmonary fibrosis and to characterize the pharmacokinetic disposition of pirfenidone in patients with idiopathic pulmonary fibrosis.

This is a Phase 3, randomized, double blind, placebo-controlled, three-arm, safety and efficacy study of pirfenidone in patients with idiopathic pulmonary fibrosis. Approximately 400 patients at approximately 70 centers will be randomly assigned (2:2:1) to receive either 2403 milligrams (mg) of pirfenidone, placebo equivalent, or 1197 mg of pirfenidone administered in divided doses three times per day (TID) with food. Patients will be randomized by geographic region.

Patients will receive blinded study treatment from the time of randomization until the last patient randomized has been treated for 72 weeks. A Data Monitoring Committee (DMC) will periodically review safety and efficacy data to ensure patient safety.

After week 72, patients who meet the Progression of Disease (POD) definition, which is a ≥ 10% absolute decrease in percent predicted FVC or a ≥ 15% absolute decrease in percent predicted carbon monoxide diffusing capacity (DLco), will be eligible to receive permitted IPF therapies in addition to their blinded study drug. Permitted IPF therapies include corticosteroids, azathioprine, cyclophosphamide and N-acetyl-cysteine (with restrictions).

Primary Inclusion criteria:

• diagnosis of idiopathic pulmonary fibrosis
• 40 to 80 years of age
• Forced Vital Capacity greater than or equal to 50% predicted value
• Carbon monoxide diffusing capacity greater than or equal to 35% predicted value
• either Forced Vital Capacity or Carbon monoxide diffusing capacity less than or equal to 90% predicted value
• no improvement in past year
• able to walk 150 meters in 6 minutes and maintain saturation greater than or equal to 83% while on no more than 6 liters per minute (L/min) supplemental oxygen

Primary Exclusion criteria:

• unable to undergo pulmonary function testing
• evidence of significant obstructive lung disease or airway hyper-responsiveness
• in opinion of investigator patient is expected to need and be eligible for a lung transplant within 72 weeks after randomization
• active infection
• liver disease
• cancer or other medical condition likely to result in death within 2 years
• diabetes
• pregnancy or lactation
• substance abuse
• personal or family history of long QT (Q wave,T wave) syndrome
• other IPF treatment
• unable to take study medication
• withdrawal from other IPF trials