| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Idiopathic Pulmonary Fibrosis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Idiopathic Pulmonary Fibrosis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10021240 |
| E.1.2 | Term | Idiopathic pulmonary fibrosis |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• To compare the incidence of gastrointestinal AEs in patients treated with IPF, initiating pirfenidone for the first time, according to the type of diet (MUFA vs SFA). Gastrointestinal AEs rates between study groups will be evaluated during the first 16 weeks of pirfenidone treatment.
Any gastrointestinal AE related to pirfenidone treatment, including nausea, diarrhea, dyspepsia, reflux, vomiting, stomach discomfort, and abdominal distension, will be studied. |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the characteristics of the patients in both arms, including associated epidemiological parameters
• Severity (according to the Common Terminology Criteria {CTC} grading for Adverse Events version 4.0), frequency, duration of the gastrointestinal side effects, discontinuation of treatment, dose reduction and hospitalization due to these side effects.
• Specific variables of the diet that may interfere in gastric treatment-emergent side effects:
o Number of daily meals
o Method of cooking the food
o Use of butter/oil in cooking
o Quantity and variety of foods
• Other factors that may act on gastric function and drug absorption: weight, use of proton pump inhibitors (PPI), gastro-prokinetics (such as Cisapride, Domperidone, and Metoclopromide) |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Sub-study to evaluate the pharmacokinetics of pirfenidone according to type of diet in patients with idiopathic pulmonary fibrosis. |
|
| E.3 | Principal inclusion criteria |
• Signed Informed Consent Form
• Ability to comply with the study protocol in the opinion of the Investigator
• Age > 40 years
• Diagnosis of IPF at least 1 week prior to study baseline and no more than 5 years.
• Confirmation of IPF diagnosis by the Investigator of each Centre, in accordance with the 2011 international consensus guidelines (Raghu et al. 2011), at baseline.
• IPF that meet criteria for pirfenidone treatment initiation according to local reimbursement policy
• Approval of potential study participation by Central Committee (FFQ shows a clear diet predominance, MUFA or SFA).
Defined and regular diet for at least six months prior to baseline (i.e. no frequent changes in the type of diet).
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of <1% per year during the Treatment Period and for at least 58 days after the last dose of study treatment
o A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a post-menopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
o Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
o The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
• For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
o With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the Treatment Period and for at least 118 days after the last dose of trial treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period. |
|
| E.4 | Principal exclusion criteria |
• History of coexistent and clinically significant (in the opinion of the Investigator) COPD (including chronic bronchitis, emphysema), bronchiectasis, asthma, inadequately treated sleep-disordered breathing, or any clinically significant pulmonary diseases or disorders other than IPF.
• History of any connective tissue disease, including, but not limited to: rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, or mixed connective tissue disease
• History of clinically significant environmental exposure to agents known to cause pulmonary fibrosis, including asbestos, beryllium, silica, and other occupational dusts; amiodarone, nitrofurantoin, and other drugs; radiation; and birds, feathers, molds, and other inhaled antigens known to cause hypersensitivity pneumonitis
• Participation in any other investigational trial throughout the study
• Any serious medical condition that, in the opinion of the Investigator, may pose an additional risk in administering study treatment to the patient
• Certain laboratory abnormalities or findings at baseline, including:
o Total bilirubin > 5 of the upper limit of normal (ULN)
o AST/SGOT or ALT/SGPT >1.5 ULN
o Alkaline phosphatase >2.0 ULN
o Creatinine clearance <40 mL/min, calculated using the Cockcroft-Gault formula
• Pregnant or lactating, or intending to become pregnant during the study
• Pharmacological treatments (concomitant-therapy) at baseline that may cause patient gastrointestinal side effects
• Major gastro-intestinal disorders at baseline (gastric or bowel surgery, ulcus). Patients with gastroesophagic reflux or other minor digestive disorders can be included.
• Pregnant patients, or women of child-bearing potential, not using a reliable contraceptive method
• Planning to change the type of diet in the next 4 months
• Not able to follow a specific type of diet or cannot be allocated to a specific type of diet (MUFA vs SFA) by the Central Committee
• Previous intolerance or allergy to pirfenidone or hypersensitivity to the active substance or to any of the excipients |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• To compare the incidence of gastrointestinal AEs in patients treated with IPF, initiating pirfenidone for the first time, according to the type of diet (MUFA vs SFA). Gastrointestinal AEs rates between study groups will be evaluated during the first 16 weeks of pirfenidone treatment.
Any gastrointestinal AE related to pirfenidone treatment, including nausea, diarrhea, dyspepsia, reflux, vomiting, stomach discomfort, and abdominal distension, will be studied. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| Baseline characteristics of MUFA and SFA subjects will be described and evaluated using mean and standard deviation for continuous symmetric variables, median and interquartile range (Q1-Q3) for non-symmetric variables and absolute and relative frequencies for categorical variables. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| 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 | No |
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 6 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 18 |
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