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

Idiopathic Pulmonary Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02598193
• Other study ID #: MA29895
• Secondary ID: 2015-003280-11
• Status: Completed
• Phase: Phase 4
• Start date: January 14, 2016
• Est. completion date: May 16, 2017

Study information

• Verified date: May 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: May 16, 2017
• Est. primary completion date: May 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• Nintedanib
Participants with IPF will receive nintedanib at the 200-300 mg/day dose up to 24 weeks.
• Pirfenidone
Participants with IPF will receive pirfenidone at 1602-2403 mg/day dose up to 24 weeks.

Locations

Country	Name	City	State
Canada	South Health Campus/Alberta Health Services/ University of Calgary	Calgary	Alberta
Canada	University Health Network	Toronto	Ontario
Denmark	Gentofte Hospital, Lungemedicinsk Afdeling	Hellerup
France	Hopital Avicenne; Pneumologie	Bobigny
France	Hopital Louis Pradel; Pneumologie	Bron
France	Hopital de Pontchaillou; Service de Pneumologie	Rennes
Germany	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
Italy	ASST DI MONZA; U O Clinica Pneumologica	Monza	Lombardia
Italy	A.O. Universitaria San Luigi Gonzaga di Orbassano; Malattie Apparato Respiratorio (MAR2)	Orbassano	Piemonte
Italy	Azienda Ospedaliero Universitaria Pisana; U.O. Pneumologia	Pisa	Toscana
Italy	A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare	Siena	Toscana
Netherlands	Antonius Ziekenhuis; Dept of Lung Diseases	Nieuwegein
Netherlands	Erasmus MC; Afdeling Longziekten	Rotterdam
Spain	Hospital del Henares; Medicina Interna. Unidad de Neumología	Coslada (Madrid)	Madrid
Spain	Hospital Universitari de Bellvitge ; Servicio de Neumologia	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario de Canarias; Servicio de Neumologia	La Laguna	Tenerife
Spain	Complejo Asistencial Universitario de Leon; Pneumology	Leon
Spain	Hospital Universitario La Princesa; Servicio de Neumologia	Madrid
Spain	Hospital Universitario Virgen del Rocio; Servicio de Neumologia	Sevilla
Spain	Hospital General Universitario De Valencia; Servicio de Neumologia	Valencia
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina (MUSC); MUSC Pulmonary	Charleston	South Carolina
United States	Cardio-Pulmonary Associates of St. Luke's Hospital	Chesterfield	Missouri
United States	UC Health Clinical Trials Office	Cincinnati	Ohio
United States	Inova Health Care Services; Advanced Lung Disease Transplant Program	Falls Church	Virginia
United States	Pulmonix LLC	Greensboro	North Carolina
United States	David Geffen School of Medicine at UCLA;Division of Pulmonary & Critical Care/ Department of Medic	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Creighton University	Omaha	Nebraska
United States	John A. Butler, M.D. - Oregon Pulmonary Associates	Portland	Oregon
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Stanford University School of Medicine ; Pulmonary/Critical Care Medicine	Stanford	California
United States	Atlantic Respiratory Institute	Summit	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Total Number of Participant Days of Combination Treatment With Pirfenidone and Nintedanib		Baseline up to Week 24
Secondary	Total Number of Days From the Initiation of Combination Treatment to Discontinuation of Pirfenidone, Nintedanib, or Both Study Treatments		Baseline up to Week 24