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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02598193
Recruitment Status : Completed
First Posted : November 5, 2015
Results First Posted : June 13, 2018
Last Update Posted : June 13, 2018
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: Nintedanib Drug: Pirfenidone Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 89 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 14, 2016
Actual Primary Completion Date : May 16, 2017
Actual Study Completion Date : May 16, 2017

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 Name: Ofev

Drug: Pirfenidone
Participants with IPF will receive pirfenidone at 1602-2403 mg/day dose up to 24 weeks.
Other Name: Esbriet

Primary Outcome Measures :
  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 [ Time Frame: Week 24 ]

Secondary Outcome Measures :
  1. Percentage of Participants With Adverse Events and Serious Adverse Events [ Time Frame: 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.

  2. Percentage of Participants Who Discontinue Pirfenidone, Nintedanib, or Both Study Treatments Because of Adverse Events Before the Week 24 Visit [ Time Frame: Baseline up to Week 24 ]
  3. Total Number of Participant Days of Combination Treatment With Pirfenidone and Nintedanib [ Time Frame: Baseline up to Week 24 ]
  4. Total Number of Days From the Initiation of Combination Treatment to Discontinuation of Pirfenidone, Nintedanib, or Both Study Treatments [ Time Frame: Baseline up to Week 24 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02598193

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

Documents provided by Hoffmann-La Roche:
Statistical Analysis Plan  [PDF] May 17, 2017
Study Protocol  [PDF] June 21, 2016

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche Identifier: NCT02598193     History of Changes
Other Study ID Numbers: MA29895
2015-003280-11 ( EudraCT Number )
First Posted: November 5, 2015    Key Record Dates
Results First Posted: June 13, 2018
Last Update Posted: June 13, 2018
Last Verified: May 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Idiopathic Pulmonary Fibrosis
Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Interstitial
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents