Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis

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

The purposes of this study are to assess the efficacy of treatment with pirfenidone 2403 milligrams per day compared with placebo in patients with idiopathic pulmonary fibrosis (IPF)and to assess the safety of treatment with pirfenidone 2403 milligrams per day compared with placebo in patients with idiopathic pulmonary fibrosis.

This is a Phase 3, randomized, double-blind, placebo-controlled, safety and efficacy study of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF). Approximately 320 patients at approximately 50 centers will be randomly assigned (1:1) to receive pirfenidone 2403 milligrams or placebo equivalent administered in divided doses three times per day (TID) with food. The primary outcome variable will be the absolute change in percent predicted Forced Vital Capacity from Baseline to Week 72. 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 Forced Vital Capacity or a ≥ 15% absolute decrease in percent predicted carbon monoxide diffusing capacity (DLco), will be eligible to receive permitted idiopathic pulmonary fibrosis therapies in addition to their blinded study drug. Permitted idiopathic pulmonary 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 ≥ 50% predicted value
• carbon monoxide diffusing capacity (DLco) ≥ 35% predicted value
• either Forced Vital Capacity or carbon monoxide diffusing capacity (DLco) ≤ 90% predicted value
• no improvement in past year
• able to walk 150 meters in 6 minutes and maintain saturation ≥ 83% while on no more than 6 liters per minute supplemental oxygen

Primary Exclusion criteria:

• unable to undergo pulmonary function testing
• evidence of significant obstructive lung disease or airway hyper-responsiveness
• in the clinical opinion of the investigator, the patient is expected to need and be eligible for a lung transplant within 72 weeks of 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 syndrome
• other IPF treatment
• unable to take study medication
• withdrawal from other IPF trials