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

NCT ID: NCT02598193

Last Updated: 2018-06-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-14
• Study Completion Date: 2017-05-16

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.

Conditions

Idiopathic Pulmonary Fibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pirfenidone+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.

Group Type: EXPERIMENTAL

Nintedanib

Intervention Type: DRUG

Participants with IPF will receive nintedanib at the 200-300 mg/day dose up to 24 weeks.

Pirfenidone

Intervention Type: DRUG

Participants with IPF will receive pirfenidone at 1602-2403 mg/day dose up to 24 weeks.

Interventions

Nintedanib

Participants with IPF will receive nintedanib at the 200-300 mg/day dose up to 24 weeks.

Intervention Type: DRUG

Pirfenidone

Participants with IPF will receive pirfenidone at 1602-2403 mg/day dose up to 24 weeks.

Intervention Type: DRUG

Other Intervention Names

Ofev; Esbriet

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

David Geffen School of Medicine at UCLA;Division of Pulmonary & Critical Care/ Department of Medic

Los Angeles, California, United States

Stanford University School of Medicine ; Pulmonary/Critical Care Medicine

Stanford, California, United States

Sarasota Memorial Hospital

Sarasota, Florida, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Cardio-Pulmonary Associates of St. Luke's Hospital

Chesterfield, Missouri, United States

Creighton University

Omaha, Nebraska, United States

Atlantic Respiratory Institute

Summit, New Jersey, United States

Mount Sinai School of Medicine

New York, New York, United States

Columbia University Medical Center

New York, New York, 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

Medical University of South Carolina (MUSC); MUSC Pulmonary

Charleston, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Inova Health Care Services; Advanced Lung Disease Transplant Program

Falls Church, Virginia, United States

South Health Campus/Alberta Health Services/ University of Calgary

Calgary, Alberta, Canada

University Health Network

Toronto, Ontario, Canada

Gentofte Hospital, Lungemedicinsk Afdeling

Hellerup, , Denmark

Hopital Avicenne; Pneumologie

Bobigny, , France

Hopital Louis Pradel; Pneumologie

Bron, , France

Hopital de Pontchaillou; Service de Pneumologie

Rennes, , France

Fachkrankenhaus Coswig GmbH Zentrum f.Pneumologie Beatmungsmedizin Thorax-u.Gefäßchirurgie

Coswig, , Germany

Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie

Essen, , Germany

Klinikum Fulda gAG; Universitätsmedizin Marburg, Campus Fulda

Fulda, , Germany

ASST DI MONZA; U O Clinica Pneumologica

Monza, Lombardy, Italy

A.O. Universitaria San Luigi Gonzaga di Orbassano; Malattie Apparato Respiratorio (MAR2)

Orbassano, Piedmont, Italy

Azienda Ospedaliero Universitaria Pisana; U.O. Pneumologia

Pisa, Tuscany, Italy

A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare

Siena, Tuscany, Italy

Antonius Ziekenhuis; Dept of Lung Diseases

Nieuwegein, , Netherlands

Erasmus MC; Afdeling Longziekten

Rotterdam, , Netherlands

Hospital Universitari de Bellvitge ; Servicio de Neumologia

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital del Henares; Medicina Interna. Unidad de Neumología

Coslada (Madrid), Madrid, Spain

Hospital Universitario de Canarias; Servicio de Neumologia

San Cristóbal de La Laguna, Tenerife, Spain

Complejo Asistencial Universitario de Leon; Pneumology

León, , Spain

Hospital Universitario La Princesa; Servicio de Neumologia

Madrid, , Spain

Hospital Universitario Virgen del Rocio; Servicio de Neumologia

Seville, , Spain

Hospital General Universitario De Valencia; Servicio de Neumologia

Valencia, , Spain

Countries

United States; Canada; Denmark; France; Germany; Italy; Netherlands; Spain

References

Flaherty KR, Fell CD, Huggins JT, Nunes H, Sussman R, Valenzuela C, Petzinger U, Stauffer JL, Gilberg F, Bengus M, Wijsenbeek M. Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis. Eur Respir J. 2018 Aug 2;52(2):1800230. doi: 10.1183/13993003.00230-2018. Print 2018 Aug.

Reference Type: DERIVED

PMID: 29946005 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2015-003280-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MA29895

Identifier Type: -

Identifier Source: org_study_id