Clinical trial NCT02598193: Safety and Tolerability Study of Pirfenidone in Combination With Nintedanib in Participants With Idiopathic Pulmonary Fibrosis (IPF)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-11-05
Enrollment: 89
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With Adverse Events and Serious Adverse Events
timeFrame: Baseline up to Week 28
measure: Percentage of Participants Who Discontinue Pirfenidone, Nintedanib, or Both Study Treatments Because of Adverse Events Before the Week 24 Visit
timeFrame: Baseline up to Week 24
measure: Total Number of Participant Days of Combination Treatment With Pirfenidone and Nintedanib
timeFrame: Baseline up to Week 24
measure: Total Number of Days From the Initiation of Combination Treatment to Discontinuation of Pirfenidone, Nintedanib, or Both Study Treatments
timeFrame: Baseline up to Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA;Division of Pulmonary & Critical Care/ Department of Medic
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine ; Pulmonary/Critical Care Medicine
state: California
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Chesterfield
country: United States
facility: Cardio-Pulmonary Associates of St. Luke's Hospital
state: Missouri
city: Omaha
country: United States
facility: Creighton University
state: Nebraska
city: Summit
country: United States
facility: Atlantic Respiratory Institute
state: New Jersey
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Greensboro
country: United States
facility: Pulmonix LLC
state: North Carolina
city: Cincinnati
country: United States
facility: UC Health Clinical Trials Office
state: Ohio
city: Portland
country: United States
facility: John A. Butler, M.D. - Oregon Pulmonary Associates
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC); MUSC Pulmonary
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Falls Church
country: United States
facility: Inova Health Care Services; Advanced Lung Disease Transplant Program
state: Virginia
city: Calgary
country: Canada
facility: South Health Campus/Alberta Health Services/ University of Calgary
state: Alberta
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Hellerup
country: Denmark
facility: Gentofte Hospital, Lungemedicinsk Afdeling
city: Bobigny
country: France
facility: Hopital Avicenne; Pneumologie
city: Bron
country: France
facility: Hopital Louis Pradel; Pneumologie
city: Rennes
country: France
facility: Hopital de Pontchaillou; Service de Pneumologie
city: Coswig
country: Germany
facility: Fachkrankenhaus Coswig GmbH Zentrum f.Pneumologie Beatmungsmedizin Thorax-u.Gefäßchirurgie
city: Essen
country: Germany
facility: Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie
city: Fulda
country: Germany
facility: Klinikum Fulda gAG; Universitätsmedizin Marburg, Campus Fulda
city: Monza
country: Italy
facility: ASST DI MONZA; U O Clinica Pneumologica
state: Lombardia
city: Orbassano
country: Italy
facility: A.O. Universitaria San Luigi Gonzaga di Orbassano; Malattie Apparato Respiratorio (MAR2)
state: Piemonte
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana; U.O. Pneumologia
state: Toscana
city: Siena
country: Italy
facility: A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare
state: Toscana
city: Nieuwegein
country: Netherlands
facility: Antonius Ziekenhuis; Dept of Lung Diseases
city: Rotterdam
country: Netherlands
facility: Erasmus MC; Afdeling Longziekten
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge ; Servicio de Neumologia
state: Barcelona
city: Coslada (Madrid)
country: Spain
facility: Hospital del Henares; Medicina Interna. Unidad de Neumología
state: Madrid
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias; Servicio de Neumologia
state: Tenerife
city: Leon
country: Spain
facility: Complejo Asistencial Universitario de Leon; Pneumology
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa; Servicio de Neumologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio; Servicio de Neumologia
city: Valencia
country: Spain
facility: Hospital General Universitario De Valencia; Servicio de Neumologia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.