Safety and Tolerability Study of Pirfenidone in Combination With Nintedanib in Participants With Idiopathic Pulmonary Fibrosis (IPF)

Phase 4

Completed

Conditions: Idiopathic Pulmonary Fibrosis

Interventions: Drug: Nintedanib
Drug: Pirfenidone

Registration Number: NCT02598193

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This clinical study will evaluate the safety and tolerability of combination treatment of nintedanib and pirfenidone in participants with IPF. Eligible participants must have received pirfenidone for at least 16 weeks on a stable dose. Nintedanib will be added on Day 1 of the study as a combination treatment for IPF for 24 weeks.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 89

Inclusion Criteria

Participants who are on pirfenidone for at least 16 weeks and on a stable dose (defined as 1602-2403 mg/day) for at least 28 days at the start of Screening; 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
Participants with percent predicted forced vital capacity (FVC) more than or equal to (>=) 50 percent (%) and percent predicted carbon monoxide diffusing capacity (DLco) >=30% at Screening
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of less than (<) 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 (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm during the treatment period and for at least 4 months after the final Follow-up Visit

Exclusion Criteria

Participants with clinical evidence of active infection
Participant with any new or ongoing moderate or severe adverse reaction considered by the Investigator to be related to pirfenidone, or an pirfenidone treatment interruption in the 28 days before the start of Screening
Any condition that is likely to result in death in the 12 months after the start of Screening
Lung transplantation anticipated or any planned significant surgical intervention
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 and/or severe renal impairment
History of gastrointestinal (GI) tract perforation, unstable or deteriorating cardiac or pulmonary disease (other than IPF), long QT syndrome, 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
Bleeding risk
Use of Cytochrome P450 (CYP) 1A2 (CYP1A2) inhibitors (for example, fluvoxamine, enoxacin) and/or use of inhibitors of P-glycoprotein (for example, ketoconazole, erythromycin) or CYP3A4 (for example, ketoconazole, erythromycin) or their inducers (for example, rifampicin, carbamazepine, phenytoin, St John's wort) in the 28 days before the start of Screening
Pregnancy or lactation
Hypersensitivity to peanuts and/or soy
Use of pirfenidone and/or nintedanib in a clinical study protocol in the 28 days before the start of screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pirfenidone+Nintedanib	Nintedanib	Participants with IPF will receive pirfenidone at 1602-2403 milligrams per day (mg/day) dose and nintedanib at the 200-300 mg/day dose up to 24 weeks.
Pirfenidone+Nintedanib	Pirfenidone	Participants with IPF will receive pirfenidone at 1602-2403 milligrams per day (mg/day) dose and nintedanib at the 200-300 mg/day dose up to 24 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Complete 24 Weeks of Combination Treatment on Pirfenidone at a Dose of 1602-2403 mg/Day and Nintedanib at a Dose of 200-300 mg/Day	Week 24

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events and Serious Adverse Events	Baseline up to Week 28	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Total Number of Participant Days of Combination Treatment With Pirfenidone and Nintedanib	Baseline up to Week 24
Percentage of Participants Who Discontinue Pirfenidone, Nintedanib, or Both Study Treatments Because of Adverse Events Before the Week 24 Visit	Baseline up to Week 24
Total Number of Days From the Initiation of Combination Treatment to Discontinuation of Pirfenidone, Nintedanib, or Both Study Treatments	Baseline up to Week 24

Trial Locations

Locations (38): Stanford University School of Medicine ; Pulmonary/Critical Care Medicine
🇺🇸
Stanford, California, United States
Mount Sinai School of Medicine
🇺🇸
New York, New York, United States
Inova Health Care Services; Advanced Lung Disease Transplant Program
🇺🇸
Falls Church, Virginia, United States
Hopital Avicenne; Pneumologie
🇫🇷
Bobigny, France
Hopital Louis Pradel; Pneumologie
🇫🇷
Bron, France
Gentofte Hospital, Lungemedicinsk Afdeling
🇩🇰
Hellerup, Denmark
Hopital de Pontchaillou; Service de Pneumologie
🇫🇷
Rennes, France
Fachkrankenhaus Coswig GmbH Zentrum f.Pneumologie Beatmungsmedizin Thorax-u.Gefäßchirurgie
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Coswig, Germany
Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie
🇩🇪
Essen, Germany
ASST DI MONZA; U O Clinica Pneumologica
🇮🇹
Monza, Lombardia, Italy
Klinikum Fulda gAG; Universitätsmedizin Marburg, Campus Fulda
🇩🇪
Fulda, Germany
Azienda Ospedaliero Universitaria Pisana; U.O. Pneumologia
🇮🇹
Pisa, Toscana, Italy
A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare
🇮🇹
Siena, Toscana, Italy
Hospital Universitario de Canarias; Servicio de Neumologia
🇪🇸
La Laguna, Tenerife, Spain
Hospital del Henares; Medicina Interna. Unidad de Neumología
🇪🇸
Coslada (Madrid), Madrid, Spain
Complejo Asistencial Universitario de Leon; Pneumology
🇪🇸
Leon, Spain
Hospital Universitario La Princesa; Servicio de Neumologia
🇪🇸
Madrid, Spain
Hospital General Universitario De Valencia; Servicio de Neumologia
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Valencia, Spain
Hospital Universitario Virgen del Rocio; Servicio de Neumologia
🇪🇸
Sevilla, Spain
University of Michigan Health System
🇺🇸
Ann Arbor, Michigan, United States
Medical University of South Carolina (MUSC); MUSC Pulmonary
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Charleston, South Carolina, United States
South Health Campus/Alberta Health Services/ University of Calgary
🇨🇦
Calgary, Alberta, Canada
Antonius Ziekenhuis; Dept of Lung Diseases
🇳🇱
Nieuwegein, Netherlands
Erasmus MC; Afdeling Longziekten
🇳🇱
Rotterdam, Netherlands
Hospital Universitari de Bellvitge ; Servicio de Neumologia
🇪🇸
Hospitalet de Llobregat, Barcelona, Spain
David Geffen School of Medicine at UCLA;Division of Pulmonary & Critical Care/ Department of Medic
🇺🇸
Los Angeles, California, United States
Cardio-Pulmonary Associates of St. Luke's Hospital
🇺🇸
Chesterfield, Missouri, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Sarasota Memorial Hospital
🇺🇸
Sarasota, Florida, United States
University Health Network
🇨🇦
Toronto, Ontario, Canada
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Pulmonix LLC
🇺🇸
Greensboro, North Carolina, United States
UC Health Clinical Trials Office
🇺🇸
Cincinnati, Ohio, United States
John A. Butler, M.D. - Oregon Pulmonary Associates
🇺🇸
Portland, Oregon, United States
A.O. Universitaria San Luigi Gonzaga di Orbassano; Malattie Apparato Respiratorio (MAR2)
🇮🇹
Orbassano, Piemonte, Italy
Columbia University Medical Center
🇺🇸
New York, New York, United States
Creighton University
🇺🇸
Omaha, Nebraska, United States
Atlantic Respiratory Institute
🇺🇸
Summit, New Jersey, United States