Trial Outcomes & Findings for A Study of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing Interstitial Lung Disease (NCT NCT03099187)

Last Updated: 2021-01-13

Results Overview

Rate of decline in FVC was measured in mL by daily handheld spirometer. The analyses were repeated due to an additional independent review of the home spirometry data.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

253 participants

Primary outcome timeframe

Up to Week 24

Results posted on

2021-01-13

Participant Flow

Participant milestones

Participant milestones
Measure	Pirfenidone Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Open-Label Treatment (Pirfenidone) After participants completed the double-blind treatment period and the follow-up visit at Week 28, they were offered the option to receive open-label pirfenidone within the trial protocol in a safety follow-up period of up to 12 months. A final follow-up visit was performed at the end of the safety period, 28 days after the last open-label dose.	Open-Label Treatment (Placebo) After participants completed the double-blind treatment period and the follow-up visit at Week 28, they were offered the option to receive open-label pirfenidone within the trial protocol in a safety follow-up period of up to 12 months. A final follow-up visit was performed at the end of the safety period, 28 days after the last open-label dose.
Double-blind Treatment STARTED	127	126	0	0
Double-blind Treatment COMPLETED	94	110	0	0
Double-blind Treatment NOT COMPLETED	33	16	0	0
12-month Safety Follow-up STARTED	0	0	94	110
12-month Safety Follow-up COMPLETED	0	0	75	84
12-month Safety Follow-up NOT COMPLETED	0	0	19	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Pirfenidone Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Open-Label Treatment (Pirfenidone) After participants completed the double-blind treatment period and the follow-up visit at Week 28, they were offered the option to receive open-label pirfenidone within the trial protocol in a safety follow-up period of up to 12 months. A final follow-up visit was performed at the end of the safety period, 28 days after the last open-label dose.	Open-Label Treatment (Placebo) After participants completed the double-blind treatment period and the follow-up visit at Week 28, they were offered the option to receive open-label pirfenidone within the trial protocol in a safety follow-up period of up to 12 months. A final follow-up visit was performed at the end of the safety period, 28 days after the last open-label dose.
Double-blind Treatment Adverse Event	19	1	0	0
Double-blind Treatment Death	1	3	0	0
Double-blind Treatment Lack of Efficacy	1	0	0	0
Double-blind Treatment Physician Decision	2	1	0	0
Double-blind Treatment Withdrawal by Subject	9	4	0	0
Double-blind Treatment Lung transplantation	0	1	0	0
Double-blind Treatment Non-compliance with study drug	0	2	0	0
Double-blind Treatment Disease progression	0	1	0	0
Double-blind Treatment Randomization error	0	2	0	0
Double-blind Treatment Non-compliance with Protocol procedure	1	1	0	0
12-month Safety Follow-up Adverse Event	0	0	5	12
12-month Safety Follow-up Death	0	0	7	9
12-month Safety Follow-up Lung transplantation	0	0	2	1
12-month Safety Follow-up Lost to Follow-up	0	0	1	0
12-month Safety Follow-up Symptomatic deterioration	0	0	1	1
12-month Safety Follow-up Withdrawal by Subject	0	0	3	2
12-month Safety Follow-up Due to hospitalization	0	0	0	1

Baseline Characteristics

A Study of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing Interstitial Lung Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24. After participants completed the double-blind treatment period and the follow-up visit at Week 28, they were offered the option to receive open-label pirfenidone within the trial protocol in a safety follow-up period of up to 12 months. A final follow-up visit was performed at the end of the safety period, 28 days after the last open-label dose.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24. After participants completed the double-blind treatment period and the follow-up visit at Week 28, they were offered the option to receive open-label pirfenidone within the trial protocol in a safety follow-up period of up to 12 months. A final follow-up visit was performed at the end of the safety period, 28 days after the last open-label dose.	Total n=253 Participants Total of all reporting groups
Age, Continuous	68.0 Years STANDARD_DEVIATION 10.1 • n=93 Participants	67.7 Years STANDARD_DEVIATION 9.2 • n=4 Participants	67.8 Years STANDARD_DEVIATION 9.6 • n=27 Participants
Sex: Female, Male Female	57 Participants n=93 Participants	57 Participants n=4 Participants	114 Participants n=27 Participants
Sex: Female, Male Male	70 Participants n=93 Participants	69 Participants n=4 Participants	139 Participants n=27 Participants
Race/Ethnicity, Customized Hispanic or Latino	7 Participants n=93 Participants	9 Participants n=4 Participants	16 Participants n=27 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	115 Participants n=93 Participants	112 Participants n=4 Participants	227 Participants n=27 Participants
Race/Ethnicity, Customized Not reported	5 Participants n=93 Participants	5 Participants n=4 Participants	10 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Asian	5 Participants n=93 Participants	0 Participants n=4 Participants	5 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Race/Ethnicity, Customized Other	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized White	120 Participants n=93 Participants	123 Participants n=4 Participants	243 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to Week 24

Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses. Only participants for whom data were collected are included in the analysis.

Rate of decline in FVC was measured in mL by daily handheld spirometer. The analyses were repeated due to an additional independent review of the home spirometry data.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period Primary Analysis in 2019	-17.9 milliliter (mL) Interval -311.7 to 275.9	116.6 milliliter (mL) Interval -451.9 to 685.2
Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period Final Analysis in 2020	-90.3 milliliter (mL) Interval -157.0 to -23.7	125.6 milliliter (mL) Interval -458.4 to 709.6

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

FVC was measured in liter (L) by spirometry. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Change in Percent Predicted FVC Baseline (Day 1)	73.95 Percent predicted (%) Standard Deviation 18.815	73.95 Percent predicted (%) Standard Deviation 19.974
Change in Percent Predicted FVC Week 4	74.04 Percent predicted (%) Standard Deviation 19.009	74.55 Percent predicted (%) Standard Deviation 21.223
Change in Percent Predicted FVC Week 8	73.98 Percent predicted (%) Standard Deviation 19.324	73.50 Percent predicted (%) Standard Deviation 20.168
Change in Percent Predicted FVC Week 12	73.96 Percent predicted (%) Standard Deviation 19.493	73.91 Percent predicted (%) Standard Deviation 20.856
Change in Percent Predicted FVC Week 16	74.56 Percent predicted (%) Standard Deviation 20.299	72.65 Percent predicted (%) Standard Deviation 22.479
Change in Percent Predicted FVC Week 20	73.94 Percent predicted (%) Standard Deviation 21.000	71.99 Percent predicted (%) Standard Deviation 21.673
Change in Percent Predicted FVC Week 24	72.95 Percent predicted (%) Standard Deviation 20.819	73.55 Percent predicted (%) Standard Deviation 22.383

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

FVC was measured in liter (L) by spirometry. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Change in FVC Baseline	2.36 Liter (L) Standard Deviation 0.793	2.38 Liter (L) Standard Deviation 0.747
Change in FVC Week 4	2.37 Liter (L) Standard Deviation 0.818	2.37 Liter (L) Standard Deviation 0.786
Change in FVC Week 8	2.37 Liter (L) Standard Deviation 0.822	2.36 Liter (L) Standard Deviation 0.816
Change in FVC Week 12	2.37 Liter (L) Standard Deviation 0.820	2.35 Liter (L) Standard Deviation 0.773
Change in FVC Week 16	2.41 Liter (L) Standard Deviation 0.860	2.31 Liter (L) Standard Deviation 0.782
Change in FVC Week 20	2.40 Liter (L) Standard Deviation 0.866	2.30 Liter (L) Standard Deviation 0.796
Change in FVC Week 24	2.37 Liter (L) Standard Deviation 0.863	2.34 Liter (L) Standard Deviation 0.773

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.

Categorical change in FVC was measured both by daily spirometry as well as by spirometry during clinical visits. Only the site spirometry data were used as the daily spirometry data were not normally distributed. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Categorical Change in FVC of >5% Primary Analysis in 2019	47 Number of Participants	74 Number of Participants
Categorical Change in FVC of >5% Final Analysis in 2020	47 Number of Participants	73 Number of Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Categorical Change in FVC of >10% Primary Analysis in 2019	18 Number of Participants	34 Number of Participants
Categorical Change in FVC of >10% Final Analysis in 2020	18 Number of Participants	33 Number of Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

The DLco is a pulmonary function test that measures the capacity for the lung to carry out gas exchange between the inhaled breath and the pulmonary capillary blood vessels and the DLco %-predicted represents the DLco expressed as a percentage of the expected normal valued based on the participant's age, height, gender and ethnicity.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) Baseline (Day 1)	46.19 % predicted Standard Deviation 12.403	49.57 % predicted Standard Deviation 13.931
Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) Change from Baseline at Week 12 (Primary Analysis in 2019)	-0.52 % predicted Standard Deviation 6.193	-0.56 % predicted Standard Deviation 8.807
Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) Change from Baseline at Week 24 (Primary Analysis in 2019)	-0.65 % predicted Standard Deviation 7.113	-2.47 % predicted Standard Deviation 8.833
Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) Change from Baseline at Week 12 (Final Analysis in 2020)	-0.52 % predicted Standard Deviation 6.193	-0.89 % predicted Standard Deviation 9.407
Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) Change from Baseline at Week 24 (Final Analysis in 2020)	-0.65 % predicted Standard Deviation 7.113	-2.48 % predicted Standard Deviation 8.893

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Comparison of 6-minute walk distance before beginning and after completing study therapy.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Change in 6-minute Walk Distance (6MWD) Baseline	391.6 meter (m) Standard Deviation 114.93	394.0 meter (m) Standard Deviation 108.09
Change in 6-minute Walk Distance (6MWD) Change from Baseline at Week 12	-14.8 meter (m) Standard Deviation 66.23	-7.7 meter (m) Standard Deviation 57.60
Change in 6-minute Walk Distance (6MWD) Change from Baseline at Week 24	-2.0 meter (m) Standard Deviation 68.11	-26.7 meter (m) Standard Deviation 79.32

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

University of California, San Diego Shortness of Breath Questionnaire (SOBQ) consists of 24-item on a scale of 0 to 5 with 0=not at all and 5=maximal or unable to do because of breathlessness. The total scores were calculated by summation of the 24 items scores and transformed into 0-100, with 0= poor quality of life , and 100= excellent quality of life.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Change in University of California, San Diego-Shortness of Breath Questionnaire Score Baseline	44.17 Scores on a Scale Standard Deviation 25.204	48.89 Scores on a Scale Standard Deviation 23.441
Change in University of California, San Diego-Shortness of Breath Questionnaire Score Change from Baseline at Week 12	1.47 Scores on a Scale Standard Deviation 19.707	2.24 Scores on a Scale Standard Deviation 18.617
Change in University of California, San Diego-Shortness of Breath Questionnaire Score Change from Baseline at Week 24	5.21 Scores on a Scale Standard Deviation 18.701	5.30 Scores on a Scale Standard Deviation 22.078

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

The Leicester Cough Questionnaire is a patient-reported questionnaire evaluating the impact of cough on quality of life. The questionnaire comprises 19 items. Each item assesses symptoms, or the impact of symptoms, over the last 2 weeks on a seven-point Likert scale. Scores in three domains (physical, psychological and social) were calculated as a mean for each domain (range 1 to 7). A total score (range 3 to 21) was also calculated by adding the domain scores together. Higher scores indicate better quality of life.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Change in Score in Leicester Cough Questionnaire Score Baseline	16.13 Scores on a Scale Standard Deviation 3.711	15.15 Scores on a Scale Standard Deviation 3.928
Change in Score in Leicester Cough Questionnaire Score Change from Baseline at Week 12 (Primary Analysis in 2019)	0.35 Scores on a Scale Standard Deviation 2.903	-0.23 Scores on a Scale Standard Deviation 3.654
Change in Score in Leicester Cough Questionnaire Score Change from Baseline at Week 24 (Primary Analysis in 2019)	0.36 Scores on a Scale Standard Deviation 2.889	0.04 Scores on a Scale Standard Deviation 3.702
Change in Score in Leicester Cough Questionnaire Score Change from Baseline at Week 12 (Final Analysis in 2020)	0.35 Scores on a Scale Standard Deviation 2.903	-0.23 Scores on a Scale Standard Deviation 3.654
Change in Score in Leicester Cough Questionnaire Score Change from Baseline at Week 24 (Final Analysis in 2020)	0.35 Scores on a Scale Standard Deviation 2.884	0.04 Scores on a Scale Standard Deviation 3.702

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Cough VAS are 100-mm linear scales on which participants indicate the severity of their cough; 0 mm represents no cough and 100 mm the worst cough ever.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Change in Cough Visual Analog Scale (VAS) Score Baseline	35.60 millimeter (mm) Standard Deviation 27.497	37.18 millimeter (mm) Standard Deviation 26.270
Change in Cough Visual Analog Scale (VAS) Score Change from Baseline at Week 12	-4.33 millimeter (mm) Standard Deviation 20.017	3.32 millimeter (mm) Standard Deviation 26.429
Change in Cough Visual Analog Scale (VAS) Score Change from Baseline at Week 24	-2.52 millimeter (mm) Standard Deviation 26.720	0.78 millimeter (mm) Standard Deviation 30.121

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

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: Symptoms (respiratory symptoms and severity); Activity (activities that cause or are limited by breathlessness); Impacts (social functioning and psychological disturbances due to airway disease). Each component sub-scores are calculated from the summed weights for the positive responses to questions. 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. It is calculated by summing all positive responses in the questionnaire and expressing the result as a percentage of the total weight for the questionnaire.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Symptoms sub-score - Baseline	49.28 Scores of a Scale Standard Deviation 21.687	53.10 Scores of a Scale Standard Deviation 21.450
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Change from Baseline in Symptoms sub-score at Week 12	-2.60 Scores of a Scale Standard Deviation 19.173	0.86 Scores of a Scale Standard Deviation 16.212
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Change from Baseline in Symptoms sub-score at Week 24	-1.69 Scores of a Scale Standard Deviation 19.186	-0.66 Scores of a Scale Standard Deviation 15.407
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Activities sub-score - Baseline	63.93 Scores of a Scale Standard Deviation 20.388	66.96 Scores of a Scale Standard Deviation 18.615
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Change from Baseline in Activities sub-score at Week 12	1.17 Scores of a Scale Standard Deviation 13.376	1.13 Scores of a Scale Standard Deviation 13.704
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Change from Baseline in Activities sub-score at Week 24	1.25 Scores of a Scale Standard Deviation 14.629	2.22 Scores of a Scale Standard Deviation 13.110
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Impacts sub-score - Baseline	37.12 Scores of a Scale Standard Deviation 20.484	41.47 Scores of a Scale Standard Deviation 20.520
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Change from Baseline in Impacts sub-score at Week 12	0.29 Scores of a Scale Standard Deviation 16.826	0.33 Scores of a Scale Standard Deviation 13.888
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Change from Baseline in Impacts sub-score at Week 24	-0.18 Scores of a Scale Standard Deviation 13.884	1.07 Scores of a Scale Standard Deviation 17.539
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Total score - Baseline	47.37 Scores of a Scale Standard Deviation 18.465	51.46 Scores of a Scale Standard Deviation 17.699
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Change from Baseline in Total score at Week 12	-0.17 Scores of a Scale Standard Deviation 13.633	0.53 Scores of a Scale Standard Deviation 11.724
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) Change from Baseline in Total score at Week 24	0.05 Scores of a Scale Standard Deviation 12.549	0.85 Scores of a Scale Standard Deviation 13.383

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.

Participants with non-elective hospitalization are reported.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause All-cause hospitalization	16 Number of Participants	13 Number of Participants
Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause Respiratory-related hospitalization	5 Number of Participants	5 Number of Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.

Percentage of participants with acute exacerbation arereported.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Percentage of Participants With Investigator-reported Acute Exacerbations	3.9 Percentage of Participants	5.6 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.

Time to first investigator reported acute exacerbations from start of treatment are reported.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Time to First Investigator-reported Acute Exacerbations	NA Weeks The end point could not be analyzed due to the limited number of events.	NA Weeks The end point could not be analyzed due to the limited number of events.

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.

PFS is defined as the time to the first occurrence of a \>10% absolute decline in percent predicted FVC, a \>50 m decline of 6MWD, or death.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Progression-free Survival (PFS)	25.14 Week Interval 24.14 to The end point could not be analyzed due to the limited number of events.	24.71 Week Interval 24.14 to The end point could not be analyzed due to the limited number of events.

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.

PFS is defined as the time to the first occurrence of a \>10% relative decline in percent predicted FVC, non-elective respiratory hospitalization, or death.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Progression-free Survival (PFS)	NA Week Interval 24.86 to The median was not reached in this analysis, thus an estimate cannot be calculated. In order to calculate the median time at least 50% of participants should report an event and this is not the case in this analysis due to low event number.	NA Week Interval 24.14 to The median was not reached in this analysis, thus an estimate cannot be calculated. In order to calculate the median time at least 50% of participants should report an event and this is not the case in this analysis due to low event number.

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.

Time to first documented death from start of treatment is reported.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Time to Death From Any Cause	NA Week The end point could not be analyzed due to the limited number of events.	NA Week The end point could not be analyzed due to the limited number of events.

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.

Time to first documented death due to respiratory diseases from start of treatment will be reported.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=126 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Time to Death From Respiratory Diseases	NA Week The end point could not be analyzed due to the limited number of events.	NA Week The end point could not be analyzed due to the limited number of events.

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 28

Population: The safety population was defined as all participants with at least one intake of pirfenidone or placebo, i.e., at least one record in the drug-log of the double-blind period with a non-zero dose. Participants in the safety population were assigned to a treatment arm according to the actual treatment they received.

An adverse event is any untoward medical occurrence in a subject 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

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=124 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	120 Participants	101 Participants

SECONDARY outcome

Timeframe: From administration of the first dose of study drug to Week 24

Number of participants with dose reduction and treatment interruptions are reported.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=124 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period Participants with at least one dose modification	51 Number of Participants	34 Number of Participants
Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period Participants with at least one dose interruption	40 Number of Participants	12 Number of Participants

SECONDARY outcome

Timeframe: From the Follow-up Visit at Week 28 through the follow-up period of 12 Months

Number of participants with dose reduction and treatment interruptions are reported.

Outcome measures

Outcome measures
Measure	Pirfenidone n=94 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=110 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up Participants with at least one dose modification	41 Number of Participants	60 Number of Participants
Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up Participants with at least one dose interruption	24 Number of Participants	34 Number of Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 24

Number of participants withdrawn from trial treatment or trial discontinuations are reported.

Outcome measures

Outcome measures
Measure	Pirfenidone n=127 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=124 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the Double-Blind Period	25 Number of Participants	12 Number of Participants

SECONDARY outcome

Timeframe: From the Follow-up Visit at Week 28 through the follow-up period of 12 Months

Number of participants withdrawn from trial treatment or trial discontinuations are reported.

Outcome measures

Outcome measures
Measure	Pirfenidone n=94 Participants Participants received pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.	Placebo n=110 Participants Participants received matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the 12-month Safety Follow-up	19 Number of Participants	26 Number of Participants

Adverse Events

Pirfenidone

Serious events: 18 serious events

Other events: 107 other events

Deaths: 4 deaths

Placebo

Serious events: 20 serious events

Other events: 81 other events

Deaths: 7 deaths

Open-Label Treatment (Pirfenidone)

Serious events: 26 serious events

Other events: 64 other events

Deaths: 7 deaths

Open-Label Treatment (Placebo)

Serious events: 27 serious events

Other events: 86 other events

Deaths: 9 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