Trial Outcomes & Findings for Safety and Tolerability Study of Pirfenidone in Combination With Nintedanib in Participants With Idiopathic Pulmonary Fibrosis (IPF) (NCT NCT02598193)

NCT ID: NCT02598193

Last Updated: 2018-06-13

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 89 participants
• Primary outcome timeframe: Week 24
• Results posted on: 2018-06-13

Participant Flow

Participants with idiopathic pulmonary fibrosis were recruited for this study.

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.

Participant milestones

Measure	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.
Overall Study STARTED	89
Overall Study COMPLETED	73
Overall Study NOT COMPLETED	16

Reasons for withdrawal

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

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Pirfenidone+Nintedanib n=89 Participants 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.
Age, Continuous	68.2 Years STANDARD_DEVIATION 6.82 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	71 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	74 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants
Race/Ethnicity, Customized White	84 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian/White	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.

Outcome measures

Measure	Pirfenidone+Nintedanib n=89 Participants 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.
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	77.5 Percentage of Participants Interval 67.4 to 85.7

SECONDARY outcome

Timeframe: Baseline up to Week 28

Population: Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.

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.

Outcome measures

Measure	Pirfenidone+Nintedanib n=89 Participants 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.
Percentage of Participants With Adverse Events and Serious Adverse Events Adverse Event	98.9 Percentage of Participants
Percentage of Participants With Adverse Events and Serious Adverse Events Serious Adverse Event	18.0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.

Outcome measures

Measure	Pirfenidone+Nintedanib n=13 Participants 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.
Percentage of Participants Who Discontinue Pirfenidone, Nintedanib, or Both Study Treatments Because of Adverse Events Before the Week 24 Visit	14.6 Percentage of Praticipants Interval 8.0 to 23.7

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.

Outcome measures

Measure	Pirfenidone+Nintedanib n=89 Participants 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.
Total Number of Participant Days of Combination Treatment With Pirfenidone and Nintedanib	13330 Participant Days

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.

Outcome measures

Measure	Pirfenidone+Nintedanib n=89 Participants 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.
Total Number of Days From the Initiation of Combination Treatment to Discontinuation of Pirfenidone, Nintedanib, or Both Study Treatments	149.8 Number of Days Standard Deviation 43.93

Adverse Events

Pirfenidone+Nintedanib

Serious events: 16 serious events

Other events: 83 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pirfenidone+Nintedanib n=89 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.4% 3/89 • Number of events 3 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	2.2% 2/89 • Number of events 2 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Infections and infestations Cholecystitis infective	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Infections and infestations Influenza	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Infections and infestations Pneumonia	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Infections and infestations Tracheobronchitis	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Gastrointestinal disorders Pancreatitis	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Hepatobiliary disorders Cholelithiasis	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Injury, poisoning and procedural complications Concussion	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Nervous system disorders Transient ischaemic attack	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Vascular disorders Deep vein thrombosis	1.1% 1/89 • Number of events 1 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.

Other adverse events

Measure	Pirfenidone+Nintedanib n=89 participants at risk 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.
Gastrointestinal disorders Diarrhoea	58.4% 52/89 • Number of events 184 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Gastrointestinal disorders Nausea	49.4% 44/89 • Number of events 70 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Gastrointestinal disorders Vomiting	32.6% 29/89 • Number of events 57 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Gastrointestinal disorders Dyspepsia	9.0% 8/89 • Number of events 8 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.9% 7/89 • Number of events 7 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Gastrointestinal disorders Abdominal pain upper	6.7% 6/89 • Number of events 7 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Respiratory, thoracic and mediastinal disorders Cough	22.5% 20/89 • Number of events 22 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.2% 10/89 • Number of events 10 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Nervous system disorders Headache	14.6% 13/89 • Number of events 22 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Nervous system disorders Dizziness	10.1% 9/89 • Number of events 9 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
General disorders Fatigue	15.7% 14/89 • Number of events 16 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
General disorders Non-cardiac chest pain	5.6% 5/89 • Number of events 6 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Infections and infestations Viral upper respiratory tract infection	10.1% 9/89 • Number of events 13 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Infections and infestations Upper respiratory tract infection	9.0% 8/89 • Number of events 9 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Metabolism and nutrition disorders Decreased appetite	15.7% 14/89 • Number of events 14 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.
Investigations Weight decreased	6.7% 6/89 • Number of events 6 • Baseline up to Week 28 Safety population included all participants who had received at least one dose of investigational medicinal product on or after Day 1.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER