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

April 18, 2017 updated by: Genentech, Inc.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

435

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Brisbane, California, United States, 94005
        • InterMune, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 2403 mg/day pirfenidone
Active arm 1, 2403 mg/day pirfenidone dose group.
Drug: Pirfenidone
1197 or 2403 mg/day given orally, and administered in divided doses three times daily with food, for the duration of the study.
Active Comparator: 1197 mg/day pirfenidone
Active arm 2, 1197 mg/day pirfenidone.
Drug: Pirfenidone
1197 or 2403 mg/day given orally, and administered in divided doses three times daily with food, for the duration of the study.
Placebo Comparator: placebo
Placebo equivalent.
Drug: Placebo
Placebo equivalent, given orally, and administered in divided doses three times daily with food, for the duration of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change in Percent Predicted Forced Vital Capacity (FVC)
Time Frame: From baseline up to 72 weeks
Mean Change in Percent Predicted Forced Vital Capacity (FVC) as measured from baseline to week 72.
From baseline up to 72 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Categorical Assessment of Absolute Change in Percent Predicted Forced Vital Capacity (FVC)
Time Frame: baseline up to 72 weeks
Based on the change in baseline percent predicted FVC at week 72, patients were assigned to 1 of 5 categories: mild decline (<10% but >=0% decline), moderate decline (<20% but >=10% decline), severe decline (>=20% decline), mild improvement (>0% but <10% improvement), or moderate improvement (>=10% improvement). Those who died or had a lung transplant before Week 72 were included in the severe decline category. The results indicate the number of patients who experienced a Categorical Change in Percent Predicted Forced Vital Capacity.
baseline up to 72 weeks
Progression-free Survival (PFS)
Time Frame: Baseline to Week 72
Progression is defined as the first occurrence of a 10% absolute decline from baseline in percent predicted Forced Vital Capacity, a 15% absolute decline from baseline in percent predicted hemoglobin(Hgb)-corrected carbon monoxide diffusing capacity (DLco), or, death.
Baseline to Week 72
Change in Six-Minute Walk Test (6MWT)Distance
Time Frame: Baseline to Week 72
The change from Baseline to week 72 in distance walked during the 6-Minute Walk Test as measured in meters (m).
Baseline to Week 72
Change in Worst Oxygen Saturation by Pulse Oximetry (SpO2) Measurement Observed During the 6-Minute Walk Test
Time Frame: Baseline to Week 72
The change from baseline to week 72 in worst oxygen saturation during the 6-Minute Walk Test as measure by Pulse Oximetry (SpO2) Level is calculated as the simple difference between baseline SpO2 measurements and week 72 SpO2 measurements.
Baseline to Week 72
Change in Percent Predicted Hemoglobin (Hb)-Corrected Carbon Monoxide Diffusing Capacity (DLco) of the Lungs
Time Frame: Baseline to Week 72
Baseline to Week 72
Change in Dyspnea Score
Time Frame: Baseline to Week 72
The mean change from baseline to week 72 in Dyspnea score was measured by the University of San Diego Shortness of Breath Questionnaire (UCSD SOBQ). The SOBQ is used to assess shortness of breath with various activities of daily living (for example, brushing ones teeth or mowing the lawn). Patients rated the severity of their shortness of breath experienced on an average day during the past week on a 6 point scale (0 to 5), with 0 = not at all breathless, 4= severely breathless and 5 = Maximally or unable to do because of breathlessness.
Baseline to Week 72
Worsening of Idiopathic Pulmonary Fibrosis (IPF)
Time Frame: Time to acute IPF exacerbation, IPF-related death, lung transplant or respiratory hospitalization, whichever comes first.

Worsening of IPF was defined by the occurrence of any of the following events:

Acute IPF exacerbation, IPF-related death, Lung transplantation, or Respiratory hospitalization.
Time to acute IPF exacerbation, IPF-related death, lung transplant or respiratory hospitalization, whichever comes first.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genentech, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 14, 2006

Primary Completion (Actual)

November 10, 2008

Study Completion (Actual)

November 10, 2008

Study Registration Dates

First Submitted

February 6, 2006

First Submitted That Met QC Criteria

February 6, 2006

First Posted (Estimate)

February 7, 2006

Study Record Updates

Last Update Posted (Actual)

May 22, 2017

Last Update Submitted That Met QC Criteria

April 18, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PIPF-004
  • Capacity 2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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