E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic Pulmonary Fibrosis (IPF)
Fibrosis Pulmonar Idiopática |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- to assess the efficacy of treatment with pirfenidone 2403 mg/d compared with placebo in patients with idiopathic pulmonary fibrosis - to assess the safety of treatment with pirfenidone 2403 mg/d compared with placebo in patients with idiopathic pulmonary fibrosis
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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
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E.4 | Principal 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 liver function test criteria above specified limits: total bilirubin >2.5 x upper limit of normal (ULN); aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) >2.5 x ULN; alkaline phosphatase >2.5 x ULN 24. Screening or Baseline ECG with a QTcB interval >500 msec 25. Prior use of pirfenidone or known hypersensitivity to any of the components of study treatment 26. Investigational therapy (i.e., agents that are not approved by local regulatory agencies) for any indication within 28 days prior to screening 27. The following therapies are excluded within 28 days prior to screening: a. Any cytotoxic/immunosuppressive agent including but not limited to corticosteroids, azathioprine, cyclophosphamide, methotrexate, and cyclosporine b. Any cytokine modulators (including but not limited to etanercept, infliximab) c. Any other therapy that has been investigated or used off-label as a treatment for IPF including but not limited to d-penicillamine, colchicine, bosentan, N-acetyl-cysteine (NAC), imatinib mesylate, and Interferon gamma-1b (IFN-γ 1b)
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E.5 End points |
E.5.1 | Primary end point(s) |
The absolute change in percent predicted FVC from baseline to week 60. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |