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

This study has been completed.
Sponsor:
Information provided by:
InterMune
ClinicalTrials.gov Identifier:
NCT00287716
First received: February 6, 2006
Last updated: May 12, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Idiopathic Pulmonary Fibrosis
Drug: Pirfenidone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo Controlled, Phase 3, Three-Arm Study of the Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis

Resource links provided by NLM:


Further study details as provided by InterMune:

Primary Outcome Measures:
  • Absolute Change in Percent Predicted Forced Vital Capacity (FVC) [ Time Frame: From baseline up to 72 weeks ] [ Designated as safety issue: No ]
    Mean Change in Percent Predicted Forced Vital Capacity (FVC) as measured from baseline to week 72.


Secondary Outcome Measures:
  • Categorical Assessment of Absolute Change in Percent Predicted Forced Vital Capacity (FVC) [ Time Frame: baseline up to 72 weeks ] [ Designated as safety issue: No ]
    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.

  • Progression-free Survival (PFS) [ Time Frame: Baseline to Week 72 ] [ Designated as safety issue: No ]
    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.

  • Change in Six-Minute Walk Test (6MWT)Distance [ Time Frame: Baseline to Week 72 ] [ Designated as safety issue: No ]
    The change from Baseline to week 72 in distance walked during the 6-Minute Walk Test as measured in meters (m).

  • Change in Worst Oxygen Saturation by Pulse Oximetry (SpO2) Measurement Observed During the 6-Minute Walk Test [ Time Frame: Baseline to Week 72 ] [ Designated as safety issue: No ]
    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.

  • Change in Percent Predicted Hemoglobin (Hb)-Corrected Carbon Monoxide Diffusing Capacity (DLco) of the Lungs [ Time Frame: Baseline to Week 72 ] [ Designated as safety issue: No ]
  • Change in Dyspnea Score [ Time Frame: Baseline to Week 72 ] [ Designated as safety issue: No ]
    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.

  • Worsening of Idiopathic Pulmonary Fibrosis (IPF) [ Time Frame: Time to acute IPF exacerbation, IPF-related death, lung transplant or respiratory hospitalization, whichever comes first. ] [ Designated as safety issue: No ]

    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.



Enrollment: 435
Study Start Date: June 2006
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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).

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00287716

Locations
United States, California
InterMune, Inc.
Brisbane, California, United States, 94005
Sponsors and Collaborators
InterMune
Investigators
Study Director: Bill Bradford, MD PhD InterMune
  More Information

No publications provided by InterMune

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bill Bradford, MD, PhD / Vice President, InterMune, Inc.
ClinicalTrials.gov Identifier: NCT00287716     History of Changes
Other Study ID Numbers: PIPF-004, Capacity 2
Study First Received: February 6, 2006
Results First Received: June 2, 2010
Last Updated: May 12, 2011
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: National Institute of Health
Mexico: Ministry of Health
Poland: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by InterMune:
Idiopathic
Pulmonary
Fibrosis
Lung
Pirfenidone
InterMune

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
Pirfenidone
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 29, 2014