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

• ClinicalTrials.gov Identifier: NCT02598193
• Recruitment Status: Completed
• First Posted: November 5, 2015
• Results First Posted: June 13, 2018
• Last Update Posted: June 13, 2018
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: November 4, 2015
• First Posted Date: November 5, 2015
• Results First Submitted Date: May 16, 2018
• Results First Posted Date: June 13, 2018
• Last Update Posted Date: June 13, 2018
• Actual Study Start Date: January 14, 2016
• Actual Primary Completion Date: May 16, 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 16, 2018): 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 ]
• Original Primary Outcome Measures (submitted: November 4, 2015): 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: Up to Week 24 ]

Current Secondary Outcome Measures (submitted: May 16, 2018)

• 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.
• 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 ]
• Total Number of Participant Days of Combination Treatment With Pirfenidone and Nintedanib [ Time Frame: Baseline up to Week 24 ]
• 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 ]

Original Secondary Outcome Measures (submitted: November 4, 2015)

• Percentage of Participants with Adverse Events and Serious Adverse Events [ Time Frame: Up to Week 24 ]
• Percentage of Participants Who Discontinue Pirfenidone, Nintedanib, or Both Study Treatments Because of Adverse Events Before the Week 24 Visit [ Time Frame: Up to Week 24 ]
• Total Number of Participants Days of Combination Treatment With Pirfenidone and Nintedanib [ Time Frame: Up to Week 24 ]
• Total Number of Days From the Initiation of Combination Treatment to Discontinuation of Pirfenidone, Nintedanib, or Both Study Treatments [ Time Frame: Up to Week 24 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Idiopathic Pulmonary Fibrosis

Intervention

• 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

Study Arms

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.

Interventions:

• Drug: Nintedanib
• Drug: Pirfenidone

• 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). pii: 1800230. doi: 10.1183/13993003.00230-2018. Print 2018 Aug. Erratum in: Eur Respir J. 2018 Oct 4;52(4):.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 11, 2017): 89
• Original Estimated Enrollment (submitted: November 4, 2015): 80
• Actual Study Completion Date: May 16, 2017
• Actual Primary Completion Date: May 16, 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Denmark, France, Germany, Italy, Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT02598193
• Other Study ID Numbers: MA29895; 2015-003280-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2018