Trial Outcomes & Findings for Efficacy, Safety, and Tolerability Study of Pirfenidone in Combination With Sildenafil in Participants With Advanced Idiopathic Pulmonary Fibrosis (IPF) and Intermediate or High Probability of Group 3 Pulmonary Hypertension (NCT NCT02951429)

Last Updated: 2020-11-12

Results Overview

Disease Progression defined as relative decline in 6-minute walking distance (6MWD) from baseline (defined as \>25% from baseline or 15-25% from baseline associated with worsening oxygen saturation, worsening Borg score, or increased oxygen requirements), respiratory-related non-elective hospitalizations, or all-cause mortality.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

177 participants

Primary outcome timeframe

Baseline up to Week 52

Results posted on

2020-11-12

Participant Flow

Written informed consent for participation in the study was obtained before performing any study-specific screening tests or evaluations.

Participant milestones

Participant milestones
Measure	Pirfenidone+Sildenafil Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Overall Study STARTED	88	89
Overall Study COMPLETED	16	6
Overall Study NOT COMPLETED	72	83

Reasons for withdrawal

Reasons for withdrawal
Measure	Pirfenidone+Sildenafil Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Overall Study Adverse Event	3	7
Overall Study Death	28	36
Overall Study Lack of Efficacy	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Lung Transplantation	9	6
Overall Study Other	1	3
Overall Study Progressive Disease	1	1
Overall Study Withdrawal by Subject	7	11
Overall Study Participant ongoing in the study	23	17

Baseline Characteristics

Efficacy, Safety, and Tolerability Study of Pirfenidone in Combination With Sildenafil in Participants With Advanced Idiopathic Pulmonary Fibrosis (IPF) and Intermediate or High Probability of Group 3 Pulmonary Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.	Total n=177 Participants Total of all reporting groups
Age, Continuous	68.2 Years STANDARD_DEVIATION 7.7 • n=5 Participants	68.9 Years STANDARD_DEVIATION 7.1 • n=7 Participants	68.6 Years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	24 Participants n=7 Participants	43 Participants n=5 Participants
Sex: Female, Male Male	69 Participants n=5 Participants	65 Participants n=7 Participants	134 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	78 Participants n=5 Participants	79 Participants n=7 Participants	157 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	85 Participants n=5 Participants	88 Participants n=7 Participants	173 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Percentage of Participants With Disease Progression, as Determined by Relevant Decline in 6 Minute Walk Distance (6MWD) of At Least (>=) 15 Percent (%) From Baseline, Respiratory-Related Non-Elective Hospitalization, or Death From Any Cause	72.7 Percentage of Participants	69.7 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Time to First Occurrence of Disease Progression	26.00 Weeks Interval 20.57 to 38.14	25.43 Weeks Interval 13.0 to 37.71

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52.

Disease Progression defined as relative decline in 6MWD from baseline (defined as \>25% from baseline or 15-25% from baseline associated with worsening oxygen saturation, worsening Borg score, or increased oxygen requirements), respiratory-related non-elective hospitalizations, or all-cause mortality. In case participant had more than one event as described in the endpoint definition the second, third etc event was counted as well for the calculation of the endpoint.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Time to Multiple Occurrence of Disease Progression Events	20.57 Weeks Interval 13.14 to 26.43	13.29 Weeks Interval 12.71 to 23.29

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Percentage of Participants With Decline From Baseline in 6-minute Walking Distance (6MWD) of >= 15%	53.4 Percentage	50.6 Percentage

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Time to First Occurrence of Relevant ≥15% Decline From Baseline in 6-minute Walking Distance (6MWD)	39.00 Weeks Interval 27.86 to 52.14	38.71 Weeks Interval 25.14 to 52.57

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52.

N.A. = non-calculable

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Time to Respiratory-Related Non-Elective Hospitalization From Baseline to Week 52	54.29 Weeks Interval 36.29 to Insufficient number of participants with events.	NA Weeks Interval 42.14 to Insufficient number of participants with events.

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52.

N.A. = non-calculable

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Time to All-Cause Non-Elective Hospitalization	47.57 Weeks Interval 28.0 to Insufficient number of participants with events	49.86 Weeks Interval 32.0 to Insufficient number of participants with events

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Time to Death From Any Cause	NA Weeks Interval 54.43 to Insufficient number of participants with events	NA Weeks Insufficient number of participants with events

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Percentage of Participants With Lung Transplantation	10.2 Percentage	6.7 Percentage

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Time to Respiratory-Related Death	NA Weeks Interval 54.43 to Insufficient number of participants with events	NA Weeks Insufficient number of participants with events

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=38 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=29 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Peak Tricuspid Regurgitation Velocity	-0.014 m/s Standard Deviation 0.6326	0.103 m/s Standard Deviation 0.6699

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=41 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=30 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Pulmonary Artery Pressure (PAPs)	2.0 mmHg Standard Deviation 15.65	3.6 mmHg Standard Deviation 22.38

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=30 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=27 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Tricuspid Annular Plane Systolic Excursion (TAPSE)	-0.204 cm Standard Deviation 0.4170	-0.146 cm Standard Deviation 0.4453

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=29 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=24 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Right Ventricle Basal Diameter	0.462 cm Standard Deviation 1.2305	0.095 cm Standard Deviation 1.2875

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=24 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=22 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Inferior Vena Cava Diameter	-0.05 cm Standard Deviation 0.595	-0.09 cm Standard Deviation 0.540

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=43 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=30 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Left Ventricular Ejection Fraction (LVEF)	1.22 Percentage Standard Deviation 9.166	-0.85 Percentage Standard Deviation 5.767

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=43 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=29 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline to Week 52 in Carbon Monoxide Diffusing Capacity/ Pulmonary Diffusing Capacity (DLCO)	-2.918 Percentage Predicted Standard Deviation 6.2296	-2.440 Percentage Predicted Standard Deviation 8.2820

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=45 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=33 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline to Week 52 in Forced Vital Capacity (FVC)	-2.761 Percentage Predicted Standard Deviation 7.8044	-1.616 Percentage Predicted Standard Deviation 11.1158

SECONDARY outcome

Timeframe: Week 52

Population: Participants with data available at week 52.

The World Health Organisation (WHO) functional class system defines the severity of an participant's symptoms. Class II - Participants with Pulmonary Hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue breathlessness, fatigue (tiredness), or activities that can cause chest pain, dizziness or even black outs. Class III - Participants with Pulmonary Hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue breathlessness, fatigue (tiredness), or activities that can cause chest pain, dizziness or even black outs. Class IV - participants with pulmonary hypertension with inability to carry out any physical activity without symptoms. These participants manifest signs of right heart failure, breathlessness and /or fatigue, which may even be present at rest. Discomfort is increased by any physical activity.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=49 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=36 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Percentage of Participants by World Health Organization (WHO) Functional Class at Week 52 Class II	19.3 Percentage	13.5 Percentage
Percentage of Participants by World Health Organization (WHO) Functional Class at Week 52 Class III	33.0 Percentage	24.7 Percentage
Percentage of Participants by World Health Organization (WHO) Functional Class at Week 52 Class IV	3.4 Percentage	1.1 Percentage
Percentage of Participants by World Health Organization (WHO) Functional Class at Week 52 Missing	0 Percentage	1.1 Percentage

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=44 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=28 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Level (pg/mL) at Week 52	110.1 pg/mL) Standard Deviation 612.98	605.9 pg/mL) Standard Deviation 1273.19

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in participants with diseases of airways obstruction. Three component scores are calculated, where the higher the component result the worse the condition: Symptoms concerned with the effect of respiratory symptoms, their frequency and severity (range: 0-16.61) Activity concerned with activities that cause or are limited by breathlessness (range: 0-30.31) Impacts covers a range of aspects concerned with social functioning and psychological disturbances resulting from airway disease (range: 0- 53.08) Total score summaries the impact of disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=41 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=31 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
St. George's Respiratory Questionnaire (SGRQ) Changes From Baseline at Week 52 Total score	6.149 Units on a scale Standard Deviation 12.3407	11.437 Units on a scale Standard Deviation 12.5187
St. George's Respiratory Questionnaire (SGRQ) Changes From Baseline at Week 52 Symptoms component score	2.498 Units on a scale Standard Deviation 19.6074	8.261 Units on a scale Standard Deviation 19.5558
St. George's Respiratory Questionnaire (SGRQ) Changes From Baseline at Week 52 Activities component score	3.997 Units on a scale Standard Deviation 15.4341	10.871 Units on a scale Standard Deviation 14.5246
St. George's Respiratory Questionnaire (SGRQ) Changes From Baseline at Week 52 Impacts component score	8.417 Units on a scale Standard Deviation 15.0040	12.118 Units on a scale Standard Deviation 15.3487

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

The UCSD-SOBQ is a respiratory questionnaire and it assesses dyspnea associated with activities of daily living (ADL). Participants indicate severity of SOB on a 6-point scale in 21 ADL. Three additional questions ask about fear of harm from overexertion, limitations and fear caused by SOB. A total score ranges from 0 to 120, with higher scores indicating greater impairment.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=35 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=25 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Changes From Baseline at Week 52	12.5 Points on scale Standard Deviation 20.93	18.8 Points on scale Standard Deviation 19.68

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=42 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=30 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline in Distance Walked, 6-minute Walking Distance (6MWD) Test at Week 52	-52.9 meters Standard Deviation 121.07	-40.8 meters Standard Deviation 91.26

SECONDARY outcome

Timeframe: Baseline up to Week 52

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=42 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=30 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline in Oxygen Requirements, 6-minute Walking Distance (6MWD) Test at Week 52	0.6 L Standard Deviation 1.27	0.6 L Standard Deviation 1.43

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Participants with data available at week 52 to calculate a change from baseline.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=42 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=30 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Change From Baseline in Other 6-minute Walking Distance (6MWD) Parameters at Week 52 SpO2 before the test (at rest)	-0.5 Percentage Standard Deviation 4.63	-0.8 Percentage Standard Deviation 3.77
Change From Baseline in Other 6-minute Walking Distance (6MWD) Parameters at Week 52 SpO2 lowest during the test	-3.4 Percentage Standard Deviation 8.93	0.3 Percentage Standard Deviation 5.27
Change From Baseline in Other 6-minute Walking Distance (6MWD) Parameters at Week 52 SpO2 after the test	0.5 Percentage Standard Deviation 9.97	-2.3 Percentage Standard Deviation 6.67

SECONDARY outcome

Timeframe: Baseline up to Week 52 + 28 days

Population: Participants with AEs that started or worsened on or after first intake of randomized treatment until last positive dose + 28 days

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=88 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Percentage of Participants With Adverse Events	98.9 Percentage	93.3 Percentage

SECONDARY outcome

Timeframe: Week 52

Population: Participants with data available at week 52.

The Borg Scale rates participant's level of perceived exertion during any activity from 0-10, with 0 being no effort at all and 10 being maximal exertion.

Outcome measures

Outcome measures
Measure	Pirfenidone+Sildenafil n=42 Participants Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=30 Participants Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Borg Scale Result at the End of the Test at Week 52	0.9 Points on Scale Standard Deviation 3.00	0.7 Points on Scale Standard Deviation 3.24

Adverse Events

Pirfenidone+Sildenafil

Serious events: 54 serious events

Other events: 53 other events

Deaths: 28 deaths

Pirfenidone+Placebo

Serious events: 55 serious events

Other events: 58 other events

Deaths: 36 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

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

Measure	Pirfenidone+Sildenafil n=88 participants at risk Participants received pirfenidone along with sildenafil, orally, three times a day for 52 weeks.	Pirfenidone+Placebo n=89 participants at risk Participants received pirfenidone along with placebo matched to sildenafil, orally, three times a day for 52 weeks.
Gastrointestinal disorders Diarrhoea	12.5% 11/88 • Number of events 15 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	2.2% 2/89 • Number of events 2 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Gastrointestinal disorders Vomiting	5.7% 5/88 • Number of events 5 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	3.4% 3/89 • Number of events 3 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
General disorders Fatigue	9.1% 8/88 • Number of events 8 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	6.7% 6/89 • Number of events 6 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
General disorders Oedema peripheral	3.4% 3/88 • Number of events 4 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	5.6% 5/89 • Number of events 5 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Infections and infestations Bronchitis	6.8% 6/88 • Number of events 6 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	10.1% 9/89 • Number of events 15 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Infections and infestations Influenza	2.3% 2/88 • Number of events 2 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	5.6% 5/89 • Number of events 6 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Infections and infestations Respiratory tract infection	10.2% 9/88 • Number of events 11 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	4.5% 4/89 • Number of events 6 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Infections and infestations Upper respiratory tract infection	9.1% 8/88 • Number of events 9 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	2.2% 2/89 • Number of events 4 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Investigations Weight decreased	5.7% 5/88 • Number of events 5 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	3.4% 3/89 • Number of events 3 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Metabolism and nutrition disorders Decreased appetite	6.8% 6/88 • Number of events 6 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	10.1% 9/89 • Number of events 9 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Nervous system disorders Dizziness	5.7% 5/88 • Number of events 5 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	2.2% 2/89 • Number of events 2 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Nervous system disorders Headache	6.8% 6/88 • Number of events 7 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	2.2% 2/89 • Number of events 3 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Respiratory, thoracic and mediastinal disorders Cough	8.0% 7/88 • Number of events 9 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	10.1% 9/89 • Number of events 9 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 22/88 • Number of events 23 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	19.1% 17/89 • Number of events 18 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	9.1% 8/88 • Number of events 8 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	7.9% 7/89 • Number of events 10 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Skin and subcutaneous tissue disorders Pruritus	3.4% 3/88 • Number of events 3 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	5.6% 5/89 • Number of events 6 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.
Vascular disorders Hypotension	6.8% 6/88 • Number of events 7 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.	10.1% 9/89 • Number of events 10 • From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019. Total # of Deaths (all causes n= 64) represent deaths occurring during Double blind treatment period+4 week FU+additional safety follow up to the database snapshot of 11-Nov-2019.