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

NCT02598193 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: MA298952015-003280-11
• Study Type: interventional
• Target: 89
• Locations: 8 countries
• Sites: 38

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percentage of Participants With Adverse Events and Serious Adverse Events

  Baseline up to Week 28

• 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 Participant Days of Combination Treatment With Pirfenidone and Nintedanib

  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

Study Arms (1)

Pirfenidone+Nintedanib

EXPERIMENTAL

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.

Drug: Nintedanib; Drug: Pirfenidone

Interventions

Nintedanib DRUG

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

Also known as: Ofev

Pirfenidone+Nintedanib

Pirfenidone DRUG

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

Also known as: Esbriet

Pirfenidone+Nintedanib

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (38)

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

Los Angeles, California, 90095-1690, United States

Location

Stanford University School of Medicine ; Pulmonary/Critical Care Medicine

Stanford, California, 94305, United States

Location

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109-0666, United States

Location

Cardio-Pulmonary Associates of St. Luke's Hospital

Chesterfield, Missouri, 63017, United States

Location

Creighton University

Omaha, Nebraska, 68131, United States

Location

Atlantic Respiratory Institute

Summit, New Jersey, 07901, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Pulmonix LLC

Greensboro, North Carolina, 27403, United States

Location

UC Health Clinical Trials Office

Cincinnati, Ohio, 45267, United States

Location

John A. Butler, M.D. - Oregon Pulmonary Associates

Portland, Oregon, 97225, United States

Location

Medical University of South Carolina (MUSC); MUSC Pulmonary

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Inova Health Care Services; Advanced Lung Disease Transplant Program

Falls Church, Virginia, 22042, United States

Location

South Health Campus/Alberta Health Services/ University of Calgary

Calgary, Alberta, T3M 1M4, Canada

Location

University Health Network

Toronto, Ontario, M5G 2N2, Canada

Location

Gentofte Hospital, Lungemedicinsk Afdeling

Hellerup, 2900, Denmark

Location

Hopital Avicenne; Pneumologie

Bobigny, 93000, France

Location

Hopital Louis Pradel; Pneumologie

Bron, 69677, France

Location

Hopital de Pontchaillou; Service de Pneumologie

Rennes, 35033, France

Location

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

Coswig, 01640, Germany

Location

Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie

Essen, 45239, Germany

Location

Klinikum Fulda gAG; Universitätsmedizin Marburg, Campus Fulda

Fulda, 36043, Germany

Location

ASST DI MONZA; U O Clinica Pneumologica

Monza, Lombardy, 20900, Italy

Location

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

Orbassano, Piedmont, 10043, Italy

Location

Azienda Ospedaliero Universitaria Pisana; U.O. Pneumologia

Pisa, Tuscany, 56124, Italy

Location

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

Siena, Tuscany, 53100, Italy

Location

Antonius Ziekenhuis; Dept of Lung Diseases

Nieuwegein, 3435 CM, Netherlands

Location

Erasmus MC; Afdeling Longziekten

Rotterdam, 3000 CA, Netherlands

Location

Hospital Universitari de Bellvitge ; Servicio de Neumologia

L'Hospitalet de Llobregat, Barcelona, 08097, Spain

Location

Hospital del Henares; Medicina Interna. Unidad de Neumología

Coslada (Madrid), Madrid, 28822, Spain

Location

Hospital Universitario de Canarias; Servicio de Neumologia

San Cristóbal de La Laguna, Tenerife, 38320, Spain

Location

Complejo Asistencial Universitario de Leon; Pneumology

León, 24071, Spain

Location

Hospital Universitario La Princesa; Servicio de Neumologia

Madrid, 28006, Spain

Location

Hospital Universitario Virgen del Rocio; Servicio de Neumologia

Seville, 41013, Spain

Location

Hospital General Universitario De Valencia; Servicio de Neumologia

Valencia, 46014, Spain

Location

Related Publications (1)

• 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.

  PMID: 29946005 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

nintedanib; pirfenidone

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2015
• First Posted: November 5, 2015
• Study Start: January 14, 2016
• Primary Completion: May 16, 2017
• Study Completion: May 16, 2017
• Last Updated: June 13, 2018
• Results First Posted: June 13, 2018

Record last verified: 2018-05

Locations

IT (4); NL (2); ES (7); DE (3); FR (3); US (16); CA (2); DK (1)