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

• Conditions: Idiopathic Pulmonary Fibrosis (IPF); MedDRA version: 9.1Level: LLTClassification code 10021240Term: Idiopathic pulmonary fibrosis

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-02-16
• 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. Percent predicted FVC =50% at the screen visit and Day 1 (before randomisation). The change in FVC (measured in liters) between the Screen Visit and Day 1 must be =10% relative difference
8. Hemoglobin (Hb)-corrected carbon monoxide diffusing capacity/carbon monoxide transfer capacity (DLco) =35% of predicted value at the Screen Visit only
9. Either FVC of Hb-corrected DLco =90% of predicted value at the Screen Visit.
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 suitable for enrolment or unlikely to comply with the requirements of this study in the opinion of the investigator
2.Premature withdrawal from 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.FEV in the first second (FEV1)/FVC ratio <0.7 after administration of bronchodilator at the screen visit and day 1 before randomisation
4.Bronchodilator response defined by absolute increase of =12% and an increase of 200 mL in the predicted FEV1 or FVC or both after bronchodilator use compared to the values before bronchodilator at the screen visit and day 1 before randomisation
5. RV >120% of predicted (before administration of bronchodilator)
6.History of clinically significant environmental exposure known to cause PF (including drugs, asbestos, beryllium, radiation, domestic birds)
7.Known explanation for interstitial lung disease
8.Diagnosis of any connective tissue disease including scleroderma, systemic lupus erythematosus, and rheumatoid arthritis
9.Clinical evidence of active infection including bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis
10.In the clinical opinion of the investigator the patient is expected to need and be eligible for a lung transplant within 72 weeks after randomisation
11.Unable to undergo pulmonary function testing which includes meeting the following reproducibility standards: At screening the 2 highest acceptable FVC values must be within 0.10 liter; at day 2 the 2 highest acceptable FVC values must be within 0.10 liter; at screening, 2 of the 3 acceptable DLco values must be within 2 units (for TLco, within 0.67 SI units of each other)
12.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 (eg basal cell carcinoma)
13.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
14.History of advanced cirrhosis or clinically significant liver disease
15.History of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous 6 months including 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
16.Any condition which in the opinion of the investigator might be significantly exacerbated by the known side effects associated with the administration of pirfenidone
17.Poorly controlled diabetes (glycosolated hemoglobin [HbA1C] >10)
18.Pregnancy or lactation. Women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective methods of contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study. If abstinence is not practiced, then one of the two methods of birth control should be an oral contraceptive (e.g oral contraception and a spermicide).
19.History of alcohol or substance abuse in the past 2 years
20.History of any condition or habit associated with altered consciousness and a risk of aspiration in the past

Study & Design

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