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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02598193

Enrollment

Registered

2015-11-05

Start date

2016-01-14

Completion date

2017-05-16

Last updated

2018-06-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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.

Interventions

DRUGNintedanib

Participants with IPF will receive nintedanib at the 200-300 mg/day dose up to 24 weeks.

DRUGPirfenidone

Participants with IPF will receive pirfenidone at 1602-2403 mg/day dose up to 24 weeks.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

40 Years to 80 Years

Healthy volunteers

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

Design outcomes

Primary

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

Measure	Time frame	Description
Percentage of Participants With Adverse Events and Serious Adverse Events	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	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	—

Countries

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

Participant flow

Recruitment details

Participants with idiopathic pulmonary fibrosis were recruited for this study.

Pre-assignment details

At the start of screening, participants were on pirfenidone for at least 16 weeks and on a stable dose (1602-2403 mg/d) for at least 28 days. A total of 109 participants were screened, 20 participants were screen failures and 89 were enrolled at 36 study centers in 8 countries.

Participants by arm

Arm	Count
Pirfenidone+Nintedanib Participants with idiopathic pulmonary fibrosis (IPF) received pirfenidone at 1602-2403 milligrams per day (mg/day) dose and nintedanib at the 200-300 mg/day dose up to 24 weeks.	89
Total	89

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	13
Overall Study	Does not want to take Nintedanib	1
Overall Study	Listed in active lung transplant list	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Pirfenidone+Nintedanib
Age, Continuous	68.2 Years STANDARD_DEVIATION 6.82
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	74 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants
Race/Ethnicity, Customized Asian	1 Participants
Race/Ethnicity, Customized Asian/White	1 Participants
Race/Ethnicity, Customized Black or African American	3 Participants
Race/Ethnicity, Customized White	84 Participants
Sex: Female, Male Female	18 Participants
Sex: Female, Male Male	71 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 89
other Total, other adverse events	83 / 89
serious Total, serious adverse events	16 / 89