A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Study of the Safety and Efficacy of Pirfenidone in Patients with Idiophatic Pulmonary Fibrosis

• Conditions: Idiophatic Pulmonary Fibrosis (IPF)

• Registration Number: EUCTR2006-000138-11-IE
• Lead Sponsor: InterMune, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-02-14
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 260

Inclusion Criteria

1. Clinical symptoms consistent with IPF, including the insidious onset of
otherwise unexplained dyspnea on exertion, of more or equal to 3 months duration
2. Diagnosis of IPF, defined as first instance in which a patient was informed of
having IPF, within 48 months of randomization
3. Age 40 through 80 years, inclusive
4. High-resolution computed tomographic (HRCT) scan showing a pattern of
disease consistent with a confident (definite) radiographic diagnosis of usual
interstitial pneumonia (UIP)/IPF. For patients with surgical lung biopsy showing
definite or probable UIP, the HRCT criterion of probable (UIP)/IPF is sufficient.
5. For patients aged <50 years: open or video-assisted thoracoscopic (VATS) lung
biopsy showing definite or probable UIP within 48 months of randomization. In
addition, there are no features supporting an alternative diagnosis on
transbronchial biopsy or bronchoalveolar lavage (BAL), if performed .
6. For patients aged more than or equal to 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, within 48 months of randomization.
a. Open or VATS lung biopsy showing definite or probable UIP.
b. Transbronchial biopsy showing no features to support an alternative
diagnosis. These alternative diagnoses include but are not limited to
granulomatous disease, sarcoidosis, and hypersensitivity pneumonitis.
c. BAL showing no features to support an alternative diagnosis
7. FVC more or equal to 50% of predicted value
8. Hemoglobin (Hb)-corrected carbon monoxide diffusing capacity/carbon
monoxide transfer capacity (DLCO /TLCO) more or equal to 35% of predicted value
9. Either FVC or Hb-corrected DLCO /TLCO less or equal to 90% of predicted value
10. No evidence of improvement in measures of IPF disease severity over the
preceding year
11. Distance walked more or equal to 150 meters (492 feet) with O2 saturation more or equal to 83% on less or equal to 6 L/min of O2 during the 6-Minute Walk Test (6MWT) oxygen titration procedure performed during screening
12. Able to understand and sign a written informed consent form
13. Able to understand the importance of adherence to study treatment and the study protocol, including the concomitant medication restrictions throughout the Study Period

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Not a suitable candidate for enrollment or unlikely to comply with the requirements of this study, in the opinion of the investigator
2. Premature withdrawal from a randomized IPF clinical trial in the previous 2 years for any reason other than Sponsor decision or current participation in a clinical drug trial
3. Forced expiratory volume in the first second (FEV1)/FVC ratio <0.7 after administration of bronchodilator
4. Bronchodilator Response defined by an absolute increase in FEV1 or FVC of >12% predicted or 200 mL after bronchodilator use
5. The change in FVC between the Screen Visit and Day 1 (Baseline) cannot vary by more than 10% absolute difference and the Bronchodilator Response, Baseline FVC and FEV1/FVC ratio must all continue to meet the inclusion and exclusion criteria
6. Residual volume (RV) >120% of predicted (before administration of bronchodilator)
7. History of clinically significant environmental exposure known to cause PF (including but not limited to drugs, asbestos, beryllium, radiation, domestic birds)
8. Known explanation for interstitial lung disease, including but not limited to
radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis and cancer
9. Diagnosis of any connective tissue disease, including but not limited to scleroderma, systemic lupus erythematosus, and rheumatoid arthritis
10. Clinical evidence of active infection, including but not limited to bronchitis,
pneumonia, sinusitis, urinary tract infection, or cellulitis
11. On a lung transplantation waiting list at time of randomization
12. Unable to undergo pulmonary function testing
13. Any history of malignancy likely to result in death or significant disability or
likely to require significant medical or surgical intervention within the next 2 years. This does not include minor surgical procedures for localized carcinoma (e.g., basal cell carcinoma)
14. Any condition other than IPF which, in the opinion of the investigator, is likely to result in the death of the patient within the next 2 years
15. History of advanced cirrhosis or clinically significant liver disease
16. History of unstable or deteriorating cardiac or pulmonary disease (other than
IPF) within the previous 6 months, including but not limited to the following:
a. Myocardial infarction, unstable angina pectoris, coronary artery bypass surgery, or coronary angioplasty
b. Congestive heart failure requiring hospitalization
c. Uncontrolled arrhythmias
d. Asthma or chronic bronchitis requiring hospitalization in the last 6 months
17. Any condition, which, in the opinion of the investigator, might be significantly
exacerbated by the known side effects associated with the administration of
pirfenidone
18. Poorly controlled diabetes (defined by glycosolated hemoglobin [HbA1C] >10)
19. Pregnancy or lactation. Women of childbearing capacity are required to have a
negative serum pregnancy test before treatment and must agree to practice
abstinence or prevent pregnancy by two methods of birth control from the date
of screening through the duration of the study (i.e. oral contraception and a spermicide, diaphragm and a spermicide, etc.).
20. History of alcohol or substance abuse in the past 2 years
21. History of any condition or habit associated with altered consciousness and a
risk of aspiration in the past 2 years
22. Family or personal history of long QT-wave syndrome
23. Any of the following liv

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - to assess the efficacy of treatment with pirfenidone 2403 mg/d compared with placebo in patients with idiophatic pulmonary fibrosis<br>- to assess the safety of treatment with pirfenidone 2403 mg/d compared with placebo in patients with idiophatic pulmonary fibrosis<br>;Secondary Objective: ;Primary end point(s): The absolute change in percent predicted FVC from baseline to week 60.