A Study of the Safety and Tolerability of Pirfenidone (Esbriet) in Combination with Nintedanib (Ofev) in Patients with Idiopathic Pulmonary Fibrosis

Phase 1

Conditions: Idiopathic Pulmonary Fibrosis (IPF)
MedDRA version: 19.0Level: PTClassification code 10021240Term: Idiopathic pulmonary fibrosisSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2015-003280-11-DK

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 80

Inclusion Criteria

•Male or female, and age 40 through 80 years old
•At the start of screening, on pirfenidone for at least 16 weeks and on a stable dose for at least 28 days (in this study, a stable dose will be defined as 1602–2403 mg/d); the dose must be expected to remain in that range throughout the study
•Documented diagnosis of IPF, per the Investigator per using the criteria of the 2011 American Thoracic Society / European Respiratory Society / Japanese Respiratory Society / Latin American Thoracic Association guidelines
•Pulmonary function test results at screening, percent predicted forced vital capacity (FVC) >=50% and percent predicted carbon monoxide diffusing capacity (DLco) >= 30%
•For women of childbearing potential: agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 3 months after the final Follow-up Visit
•For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm during the treatment period and for at least for at least 3 months after the final Follow-up Visit

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 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 44

Exclusion Criteria

•Clinical evidence of any active infection which according to the judgment of the investigator may interfere with study conduct, measurement of pulmonary function, or impact the course of IPF
•In the 28 days before the start of screening, any new or ongoing moderate or severe adverse reaction considered by the Investigator to be related to pirfenidone, or an pirfenidone treatment interruption > 7 days for any reason
•Any condition that is likely to result in death in the 12 months after the start of screening
•Lung transplantation anticipated in the 12 months after the start of screening
•Known hypersensitivity to the active substance or any excipient of either pirfenidone or nintedanib
•Mild (Child Pugh A), moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment
•Severe renal impairment, including end-stage renal disease requiring dialysis
•History or risk of gastrointestinal (GI) tract perforation
•History of unstable or deteriorating cardiac or pulmonary disease in the 6 months before the start of screening
•Electrocardiogram (ECG) with a heart-rate–corrected QT interval = 500 milliseconds (ms) at screening, or a family or personal history of long QT syndrome
•Bleeding risk: genetic predisposition to bleeding, a haemorrhagic event in the 12 months before the start of screening, or abnormal laboratory coagulation parameters. Patients who require fibrinolysis, full-dose therapeutic anticoagulation, high-dose antiplatelet therapy, or other therapy that may substantially increase bleeding risk are excluded
•Use of strong CYP1A2 inhibitors, inhibitors of P-glycoprotein or CYP3A4 or their inducers in the 28 days before the start of screening
•History of alcohol or substance abuse in the 2 years before the start of screening
•Use of any tobacco product in the 12 weeks before the start of screening, or an unwillingness to abstain from their use through the final Follow-up Visit

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Proportion of patients who complete 24 weeks of combination treatment on pirfenidone at a dose of 1602–2403 milligrams/day (mg/d) and nintedanib at a dose of 200–300 mg/d;Secondary Objective: •Proportion of patients who discontinue pirfenidone, nintedanib, or both study treatments because of adverse events before the Week 24 Visit<br>•Total number of patient days of combination treatment with pirfenidone at a dose of 1602–2403 mg/d and nintedanib at a dose of 200–300 mg/d<br>•Total number of days from the initiation of combination treatment to discontinuation of pirfenidone, nintedanib, or both study treatments<br>•Frequency and timing of adverse events (AE) and serious adverse events (SAEs)<br>;Primary end point(s): •Proportion of patients who complete 24 weeks of combination treatment on pirfenidone at a dose of 1602–2403 mg/d and nintedanib at a dose of 200–300 mg/d;Timepoint(s) of evaluation of this end point: •Up to 24 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Proportion of patients who discontinue pirfenidone, nintedanib, or both study treatments because of adverse events before the Week 24 Visit<br>2. Total number of patient days of combination treatment with pirfenidone and nintedanib<br>3. Total number of days from the initiation of combination treatment to discontinuation of pirfenidone, nintedanib, or both study treatments<br>4. Incidence of adverse events (AE) and Serious Adverse Events (SAEs)<br>;Timepoint(s) of evaluation of this end point: 1-3. Up to 24 weeks<br>4. Up to 35 days after completion of combination treatment (approximately 30 weeks)<br>

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