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

An Exploratory Multicenter, Open-Label, Single Arm Study of the Safety and Tolerability of Pirfenidone (Esbriet®) in Combination With Nintedanib (Ofev®) in Patients With Idiopathic Pulmonary Fibrosis

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Nintedanib; Drug: Pirfenidone

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3M 1M4
      • South Health Campus/Alberta Health Services/ University of Calgary
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network
• Denmark
  • Hellerup, Denmark, 2900
    • Gentofte Hospital, Lungemedicinsk Afdeling
• France
  • Bobigny, France, 93000
    • Hopital Avicenne; Pneumologie
  • Bron, France, 69677
    • Hopital Louis Pradel; Pneumologie
  • Rennes, France, 35033
    • Hopital de Pontchaillou; Service de Pneumologie
• Germany
  • Coswig, Germany, 01640
    • Fachkrankenhaus Coswig GmbH Zentrum f.Pneumologie Beatmungsmedizin Thorax-u.Gefäßchirurgie
  • Essen, Germany, 45239
    • Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie
  • Fulda, Germany, 36043
    • Klinikum Fulda gAG; Universitätsmedizin Marburg, Campus Fulda
• Italy
  • Lombardia
    • Monza, Lombardia, Italy, 20900
      • ASST DI MONZA; U O Clinica Pneumologica
  • Piemonte
    • Orbassano, Piemonte, Italy, 10043
      • A.O. Universitaria San Luigi Gonzaga di Orbassano; Malattie Apparato Respiratorio (MAR2)
  • Toscana
    • Pisa, Toscana, Italy, 56124
      • Azienda Ospedaliero Universitaria Pisana; U.O. Pneumologia
    • Siena, Toscana, Italy, 53100
      • A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare
• Netherlands
  • Nieuwegein, Netherlands, 3435 CM
    • Antonius Ziekenhuis; Dept of Lung Diseases
  • Rotterdam, Netherlands, 3000 CA
    • Erasmus MC; Afdeling Longziekten
• Spain
  • Leon, Spain, 24071
    • Complejo Asistencial Universitario de Leon; Pneumology
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa; Servicio de Neumologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Neumologia
  • Valencia, Spain, 46014
    • Hospital General Universitario De Valencia; Servicio de Neumologia
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08097
      • Hospital Universitari de Bellvitge ; Servicio de Neumologia
  • Madrid
    • Coslada (Madrid), Madrid, Spain, 28822
      • Hospital del Henares; Medicina Interna. Unidad de Neumología
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias; Servicio de Neumologia
• United States
  • California
    • Los Angeles, California, United States, 90095-1690
      • David Geffen School of Medicine at UCLA;Division of Pulmonary & Critical Care/ Department of Medic
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine ; Pulmonary/Critical Care Medicine
  • Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0666
      • University of Michigan Health System
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Cardio-Pulmonary Associates of St. Luke's Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Atlantic Respiratory Institute
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • PulmonIx LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • UC Health Clinical Trials Office
  • Oregon
    • Portland, Oregon, United States, 97225
      • John A. Butler, M.D. - Oregon Pulmonary Associates
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC); MUSC Pulmonary
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Health Care Services; Advanced Lung Disease Transplant Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Nintedanib; Participants with IPF will receive nintedanib at the 200-300 mg/day dose up to 24 weeks.; Other Names: Ofev; Drug: Pirfenidone; Participants with IPF will receive pirfenidone at 1602-2403 mg/day dose up to 24 weeks.; Other Names: Esbriet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events and Serious Adverse Events	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.	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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. Erratum In: Eur Respir J. 2018 Oct 4;52(4):

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2016
• Primary Completion (Actual): May 16, 2017
• Study Completion (Actual): May 16, 2017

Study Registration Dates

• First Submitted: November 4, 2015
• First Submitted That Met QC Criteria: November 4, 2015
• First Posted (Estimate): November 5, 2015

Study Record Updates

• Last Update Posted (Actual): June 13, 2018
• Last Update Submitted That Met QC Criteria: May 16, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Protein Kinase Inhibitors; Pirfenidone; Nintedanib
• Other Study ID Numbers: MA29895; 2015-003280-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No