Safety Study of Oral Pirfenidone in Patients With Pulmonary Fibrosis/Idiopathic Pulmonary Fibrosis

Study Overview
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Brief Summary
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To assess the safety of treatment with pirfenidone (up to 3600 mg/d) in patients with pulmonary fibrosis/idiopathic pulmonary fibrosis (PF/IPF).

Detailed Description
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This study has been designed as a rollover study to collectively include safety data from various previous studies. In addition, InterMune has also initiated an Early Access Program to make pirfenidone available to a limited number of patients with idiopathic pulmonary fibrosis in the United States. This program is also being conducted under this protocol. Registration of patients with documented IPF has been closed as of October 2005.

Official Title
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An Open-Label, Phase 2 Study of the Safety of Oral Pirfenidone in Patients With Pulmonary Fibrosis/Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis, Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Pirfenidone


Participation Criteria
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Eligibility Criteria
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General Inclusion Criteria: Able to understand and sign an informed consent form Understand the importance of adherence to study treatment and the study protocol, including concomitant medication restrictions, throughout the study period Patients must be willing to travel to an approved regional center for all study-related visits Roll-Over Criteria: Entry into study through rollover has been completed Criteria for Early Access Program patients: Clinical symptoms consistent with IPF ≥3 months duration Age 40 - 85, inclusive At the time of registration with National Organization for Rare Disorders (NORD), patients with IPF must have a percent predicted forced vital capacity (FVC) of ≥50%, and percent predicted carbon monoxide diffusing capacity (DLCO) of ≥35% At the time of enrollment in PIPF-002, (screening/baseline visit) percent predicted FVC must be ≥45%, and percent predicted DLCO must be ≥30% High-resolution computed tomographic scan (HRCT) showing definite IPF. For patients with surgical lung biopsy showing definite or probable usual interstitial pneumonia (UIP), the HRCT criterion of probable IPF is sufficient For patients aged <50 years: open or video-assisted thoracoscopic (VATS) lung biopsy showing definite or probable UIP. In addition, no features supporting an alternative diagnosis on transbronchial biopsy or bronchoalveolar lavage if performed For patients aged ≥50 years: at least one of the following diagnostic findings as well as the absence of any features on specimens resulting from any of these procedures that support an alternative diagnosis: 1) Open or VATS lung biopsy showing definite or probable UIP; 2) Transbronchial biopsy showing no features to support an alternative diagnosis; 3) Bronchoalveolar lavage (BAL) showing no features to support an alternative diagnosis

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pirfenidone<br>up to 3600 mg/day of pirfenidone given orally administered in divided doses three times daily with food, for the duration of the study | Drug: Pirfenidone<br>* up to 3600 mg/day of pirfenidone given orally administered in divided doses three times daily with food, for the duration of the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Treatment-Emergent Adverse Event (AE), Serious AE (SAE), Severe AE, Life-threatening AE, Death or Discontinuation Because of an AE | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs were classified as severe (Grade 3) in following cases: marked limitation in activity; some assistance usually required; medical intervention/ therapy required, hospitalization possible. Treatment-emergent AEs were those occurring on or after the first dosing day and up to 28 days after discontinuation of study treatment, and those occurring before treatment that worsened after the first study dose. AE included serious as well as non-serious AEs. | Baseline to 28 days after the last dose of study treatment (maximum duration of treatment in study was 604 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Predicted Forced Vital Capacity (FVC) | FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out from the lungs after full inspiration in the upright position, measured in liters. Predicted FVC is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (actual FVC value in liter)/(predicted FVC) * 100% | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480 | 
| Hemoglobin (Hgb)-Corrected Percent-Predicted Carbon Monoxide Diffusing Capacity (DLco) | DLco is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. Predicted DLco is based on a formula using sex, age and height of a person. Predicted DLco = [Hbg-corrected DLco value (in milliliters per minute per millimeter mercury [mL/min/mmHg])/predicted DLco] * 100% | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480 | 
| Resting Oxygen Saturation by Pulse Oximetry (SpO2) | SpO2 is the percentage of oxygen saturation in the blood. Oxygen level (oxygen saturation) of the blood was measured using pulse oximetry on room air. | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480 | 
| Overall Survival | Survival was analyzed as time from first study dose to death (all-cause mortality) with surviving participants censored at their last available assessment. | First dosing of study treatment until death (up to 604 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary fibrosis, respiratory diseases