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

• ClinicalTrials.gov Identifier: NCT03099187
• Recruitment Status: Completed
• First Posted: April 4, 2017
• Results First Posted: January 3, 2020
• Last Update Posted: January 13, 2021
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Lung Diseases, Interstitial
• Interventions: Drug: Pirfenidone; Drug: Placebo
• Enrollment: 253

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Pirfenidone	Placebo	Open-Label Treatment (Pirfenidone)	Open-Label Treatment (Placebo)
Arm/Group Description	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.	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.	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.
Period Title: Double-blind Treatment
Started	127	126	0	0
Completed	94	110	0	0
Not Completed	33	16	0	0
Reason Not Completed
Adverse Event	19	1	0	0
Death	1	3	0	0
Lack of Efficacy	1	0	0	0
Physician Decision	2	1	0	0
Withdrawal by Subject	9	4	0	0
Lung transplantation	0	1	0	0
Non-compliance with study drug	0	2	0	0
Disease progression	0	1	0	0
Randomization error	0	2	0	0
Non-compliance with Protocol procedure	1	1	0	0
Period Title: 12-month Safety Follow-up
Started	0	0	94	110
Completed	0	0	75	84
Not Completed	0	0	19	26
Reason Not Completed
Adverse Event	0	0	5	12
Death	0	0	7	9
Lung transplantation	0	0	2	1
Lost to Follow-up	0	0	1	0
Symptomatic deterioration	0	0	1	1
Withdrawal by Subject	0	0	3	2
Due to hospitalization	0	0	0	1

Baseline Characteristics

Arm/Group Title		Pirfenidone	Placebo	Total
Arm/Group Description		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.	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 of all reporting groups
Overall Number of Baseline Participants		127	126	253
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	127 participants	126 participants	253 participants
		68.0 (10.1)	67.7 (9.2)	67.8 (9.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	127 participants	126 participants	253 participants
	Female	57 44.9%	57 45.2%	114 45.1%
	Male	70 55.1%	69 54.8%	139 54.9%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	127 participants	126 participants	253 participants
	Hispanic or Latino	7 5.5%	9 7.1%	16 6.3%
	Not Hispanic or Latino	115 90.6%	112 88.9%	227 89.7%
	Not reported	5 3.9%	5 4.0%	10 4.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	127 participants	126 participants	253 participants
	American Indian or Alaskan Native	1 0.8%	0 0.0%	1 0.4%
	Asian	5 3.9%	0 0.0%	5 2.0%
	Black or African American	1 0.8%	2 1.6%	3 1.2%
	Other	0 0.0%	1 0.8%	1 0.4%
	White	120 94.5%	123 97.6%	243 96.0%

Outcome Measures

1. Primary Outcome

Title	Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period
Description	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.
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Pirfenidone	Placebo
Arm/Group Description:		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.	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.
Overall Number of Participants Analyzed		127	126
Mean (95% Confidence Interval); Unit of Measure: milliliter (mL)
Primary Analysis in 2019	Number Analyzed	124 participants	123 participants
		-17.9; (-311.7 to 275.9)	116.6; (-451.9 to 685.2)
Final Analysis in 2020	Number Analyzed	116 participants	116 participants
		-90.3; (-157.0 to -23.7)	125.6; (-458.4 to 709.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019. Mean FVC decline comparison between treatment groups using a Student's t-test with a two-sided significance level of 0.05
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6777
	Comments	p-value was not adjusted for multiplicity and is provided for descriptive purpose only
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Group Means
	Estimated Value	-134.6
	Confidence Interval	(2-Sided) 95%; -772.4 to 503.3
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020. Mean FVC decline comparison between treatment groups using a Student's t-test with a two-sided significance level of 0.05
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4682
	Comments	p-value was not adjusted for multiplicity and is provided for descriptive purpose only
	Method	Student's t-test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Group Means
	Estimated Value	-216.0
	Confidence Interval	(2-Sided) 95%; -803.6 to 371.7
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change in Percent Predicted FVC
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Pirfenidone	Placebo
Arm/Group Description:		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.	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.
Overall Number of Participants Analyzed		127	126
Mean (Standard Deviation); Unit of Measure: Percent predicted (%)
Baseline (Day 1)	Number Analyzed	127 participants	126 participants
		73.95 (18.815)	73.95 (19.974)
Week 4	Number Analyzed	120 participants	121 participants
		74.04 (19.009)	74.55 (21.223)
Week 8	Number Analyzed	115 participants	117 participants
		73.98 (19.324)	73.50 (20.168)
Week 12	Number Analyzed	110 participants	114 participants
		73.96 (19.493)	73.91 (20.856)
Week 16	Number Analyzed	103 participants	113 participants
		74.56 (20.299)	72.65 (22.479)
Week 20	Number Analyzed	102 participants	115 participants
		73.94 (21.000)	71.99 (21.673)
Week 24	Number Analyzed	101 participants	112 participants
		72.95 (20.819)	73.55 (22.383)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0383
	Comments	[Not Specified]
	Method	rank ANCOVA
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0239
	Comments	[Not Specified]
	Method	rank ANCOVA
	Comments	[Not Specified]

3. Secondary Outcome

Title	Change in FVC
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Pirfenidone	Placebo
Arm/Group Description:		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.	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.
Overall Number of Participants Analyzed		127	126
Mean (Standard Deviation); Unit of Measure: Liter (L)
Baseline	Number Analyzed	127 participants	126 participants
		2.36 (0.793)	2.38 (0.747)
Week 4	Number Analyzed	120 participants	121 participants
		2.37 (0.818)	2.37 (0.786)
Week 8	Number Analyzed	115 participants	117 participants
		2.37 (0.822)	2.36 (0.816)
Week 12	Number Analyzed	110 participants	114 participants
		2.37 (0.820)	2.35 (0.773)
Week 16	Number Analyzed	103 participants	113 participants
		2.41 (0.860)	2.31 (0.782)
Week 20	Number Analyzed	102 participants	115 participants
		2.40 (0.866)	2.30 (0.796)
Week 24	Number Analyzed	101 participants	112 participants
		2.37 (0.863)	2.34 (0.773)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0018
	Comments	p-value was not adjusted for multiplicity and was provided for descriptive purpose only
	Method	Student's t-test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Overall Mean Difference
	Estimated Value	95.3
	Confidence Interval	(2-Sided) 95%; 35.9 to 154.6
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0096
	Comments	p-value was not adjusted for multiplicity and was provided for descriptive purpose only
	Method	Student's t-test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Overall Mean Difference
	Estimated Value	84.3
	Confidence Interval	(2-Sided) 95%; 20.7 to 147.8
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Categorical Change in FVC of >5%
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	126
Measure Type: Number; Unit of Measure: Number of Participants
Primary Analysis in 2019	47	74
Final Analysis in 2020	47	73

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0006
	Comments	p-value was not adjusted for multiplicity and was provided for descriptive purpose only
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.69
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0009
	Comments	p-value was not adjusted for multiplicity and was provided for descriptive purpose only
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95%; 0.26 to 0.71
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Categorical Change in FVC of >10%
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	126
Measure Type: Number; Unit of Measure: Number of Participants
Primary Analysis in 2019	18	34
Final Analysis in 2020	18	33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0114
	Comments	p-value was not adjusted for multiplicity and was provided for descriptive purpose only
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; 0.23 to 0.84
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0168
	Comments	p-value was not adjusted for multiplicity and was provided for descriptive purpose only
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.88
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco)
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Pirfenidone	Placebo
Arm/Group Description:		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.	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.
Overall Number of Participants Analyzed		127	126
Mean (Standard Deviation); Unit of Measure: % predicted
Baseline (Day 1)	Number Analyzed	126 participants	125 participants
		46.19 (12.403)	49.57 (13.931)
Change from Baseline at Week 12 (Primary Analysis in 2019)	Number Analyzed	110 participants	107 participants
		-0.52 (6.193)	-0.56 (8.807)
Change from Baseline at Week 24 (Primary Analysis in 2019)	Number Analyzed	97 participants	110 participants
		-0.65 (7.113)	-2.47 (8.833)
Change from Baseline at Week 12 (Final Analysis in 2020)	Number Analyzed	110 participants	108 participants
		-0.52 (6.193)	-0.89 (9.407)
Change from Baseline at Week 24 (Final Analysis in 2020)	Number Analyzed	97 participants	111 participants
		-0.65 (7.113)	-2.48 (8.893)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0874
	Comments	p-value was not adjusted for multiplicity and was provided for descriptive purpose only
	Method	rank ANCOVA
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1191
	Comments	p-values are not adjusted for multiplicity and are provided for descriptive purpose only.
	Method	rank ANCOVA
	Comments	[Not Specified]

7. Secondary Outcome

Title	Change in 6-minute Walk Distance (6MWD)
Description	Comparison of 6-minute walk distance before beginning and after completing study therapy.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Pirfenidone	Placebo
Arm/Group Description:		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.	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.
Overall Number of Participants Analyzed		127	126
Mean (Standard Deviation); Unit of Measure: meter (m)
Baseline	Number Analyzed	127 participants	126 participants
		391.6 (114.93)	394.0 (108.09)
Change from Baseline at Week 12	Number Analyzed	108 participants	110 participants
		-14.8 (66.23)	-7.7 (57.60)
Change from Baseline at Week 24	Number Analyzed	99 participants	108 participants
		-2.0 (68.11)	-26.7 (79.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0395
	Comments	p-value was not adjusted for multiplicity and was provided for descriptive purpose only
	Method	rank ANCOVA
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0299
	Comments	p-value was not adjusted for multiplicity and was provided for descriptive purpose only
	Method	rank ANCOVA
	Comments	[Not Specified]

8. Secondary Outcome

Title	Change in University of California, San Diego-Shortness of Breath Questionnaire Score
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Pirfenidone	Placebo
Arm/Group Description:		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.	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.
Overall Number of Participants Analyzed		127	126
Mean (Standard Deviation); Unit of Measure: Scores on a Scale
Baseline	Number Analyzed	113 participants	114 participants
		44.17 (25.204)	48.89 (23.441)
Change from Baseline at Week 12	Number Analyzed	86 participants	100 participants
		1.47 (19.707)	2.24 (18.617)
Change from Baseline at Week 24	Number Analyzed	84 participants	102 participants
		5.21 (18.701)	5.30 (22.078)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7788
	Comments	[Not Specified]
	Method	rank ANCOVA
	Comments	Analysis of Covariance Changes from baseline to week 24 are compared between the treatment arms using a rank ANCOVA.
Method of Estimation	Estimation Parameter	Hodges-Lehmann Median Difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -5.00 to 5.00
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8289
	Comments	Analysis of Covariance Changes from baseline to week 24 or early discontinuation visit are compared between the treatment arms using a rank ANCOVA with change from baseline as outcome variable and standardized rank baseline value as covariate
	Method	rank ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hodges-Lehmann Median Difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -5.00 to 5.00
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Change in Score in Leicester Cough Questionnaire Score
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Pirfenidone	Placebo
Arm/Group Description:		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.	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.
Overall Number of Participants Analyzed		127	126
Mean (Standard Deviation); Unit of Measure: Scores on a Scale
Baseline	Number Analyzed	127 participants	125 participants
		16.13 (3.711)	15.15 (3.928)
Change from Baseline at Week 12 (Primary Analysis in 2019)	Number Analyzed	109 participants	114 participants
		0.35 (2.903)	-0.23 (3.654)
Change from Baseline at Week 24 (Primary Analysis in 2019)	Number Analyzed	100 participants	114 participants
		0.36 (2.889)	0.04 (3.702)
Change from Baseline at Week 12 (Final Analysis in 2020)	Number Analyzed	109 participants	114 participants
		0.35 (2.903)	-0.23 (3.654)
Change from Baseline at Week 24 (Final Analysis in 2020)	Number Analyzed	100 participants	114 participants
		0.35 (2.884)	0.04 (3.702)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1872
	Comments	p-value was not adjusted for multiplicity and was provided for descriptive purpose only
	Method	rank ANCOVA
	Comments	Analysis of Covariance Changes from baseline to week 24 are compared between the treatment arms using a rank ANCOVA.
Method of Estimation	Estimation Parameter	Hodges-Lehmann Median difference
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95%; -0.45 to 1.04
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2019
	Comments	Analysis of Covariance Changes from baseline to week 24 or early discontinuation visit are compared between the treatment arms using a rank ANCOVA with change from baseline as outcome variable and standardized rank baseline value as covariate.
	Method	rank ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hodges-Lehmann Median Difference
	Estimated Value	0.27
	Confidence Interval	(2-Sided) 95%; -0.48 to 1.02
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Change in Cough Visual Analog Scale (VAS) Score
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Pirfenidone	Placebo
Arm/Group Description:		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.	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.
Overall Number of Participants Analyzed		127	126
Mean (Standard Deviation); Unit of Measure: millimeter (mm)
Baseline	Number Analyzed	127 participants	125 participants
		35.60 (27.497)	37.18 (26.270)
Change from Baseline at Week 12	Number Analyzed	109 participants	113 participants
		-4.33 (20.017)	3.32 (26.429)
Change from Baseline at Week 24	Number Analyzed	100 participants	114 participants
		-2.52 (26.720)	0.78 (30.121)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2995
	Comments	[Not Specified]
	Method	rank ANCOVA
	Comments	Analysis of Covariance Changes from baseline to week 24 are compared between the treatment arms using a rank ANCOVA.
Method of Estimation	Estimation Parameter	Hodges-Lehmann Median Difference
	Estimated Value	-2.00
	Confidence Interval	(2-Sided) 95%; -10.00 to 4.00
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3372
	Comments	Analysis of Covariance Changes from baseline to week 24 or early discontinuation visit are compared between the treatment arms using a rank ANCOVA with change from baseline as outcome variable and standardized rank baseline value as covariate.
	Method	rank ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hodges-Lehmann Median Difference
	Estimated Value	-2.00
	Confidence Interval	(2-Sided) 95%; -10.00 to 4.00
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ)
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Pirfenidone	Placebo
Arm/Group Description:		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.	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.
Overall Number of Participants Analyzed		127	126
Mean (Standard Deviation); Unit of Measure: Scores of a Scale
Symptoms sub-score - Baseline	Number Analyzed	126 participants	125 participants
		49.28 (21.687)	53.10 (21.450)
Change from Baseline in Symptoms sub-score at Week 12	Number Analyzed	107 participants	114 participants
		-2.60 (19.173)	0.86 (16.212)
Change from Baseline in Symptoms sub-score at Week 24	Number Analyzed	99 participants	113 participants
		-1.69 (19.186)	-0.66 (15.407)
Activities sub-score - Baseline	Number Analyzed	123 participants	123 participants
		63.93 (20.388)	66.96 (18.615)
Change from Baseline in Activities sub-score at Week 12	Number Analyzed	106 participants	112 participants
		1.17 (13.376)	1.13 (13.704)
Change from Baseline in Activities sub-score at Week 24	Number Analyzed	97 participants	112 participants
		1.25 (14.629)	2.22 (13.110)
Impacts sub-score - Baseline	Number Analyzed	124 participants	123 participants
		37.12 (20.484)	41.47 (20.520)
Change from Baseline in Impacts sub-score at Week 12	Number Analyzed	107 participants	111 participants
		0.29 (16.826)	0.33 (13.888)
Change from Baseline in Impacts sub-score at Week 24	Number Analyzed	97 participants	112 participants
		-0.18 (13.884)	1.07 (17.539)
Total score - Baseline	Number Analyzed	123 participants	123 participants
		47.37 (18.465)	51.46 (17.699)
Change from Baseline in Total score at Week 12	Number Analyzed	106 participants	112 participants
		-0.17 (13.633)	0.53 (11.724)
Change from Baseline in Total score at Week 24	Number Analyzed	97 participants	112 participants
		0.05 (12.549)	0.85 (13.383)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1630
	Comments	[Not Specified]
	Method	rank ANCOVA
	Comments	Analysis of Covariance Changes from baseline to week 24 are compared between the treatment arms using a rank ANCOVA.
Method of Estimation	Estimation Parameter	Hodges-Lehmann Median Difference
	Estimated Value	-1.86
	Confidence Interval	(2-Sided) 95%; -5.06 to 1.38
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1851
	Comments	Analysis of Covariance Changes from baseline to week 24 or early discontinuation visit are compared between the treatment arms using a rank ANCOVA with change from baseline as outcome variable and standardized rank baseline value as covariate.
	Method	rank ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hodges-Lehmann Median Difference
	Estimated Value	-1.74
	Confidence Interval	(2-Sided) 95%; -5.00 to 1.55
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause
Description	Participants with non-elective hospitalization are reported.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	126
Measure Type: Number; Unit of Measure: Number of Participants
All-cause hospitalization	16	13
Respiratory-related hospitalization	5	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019. All-cause non-elective hospitalization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5922
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank tests based on the time to the first event are to compare the two treatment arms.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; 0.59 to 2.49
	Estimation Comments	Hazard ratios and corresponding 95% CI are calculated by applying Cox-proportional hazard models.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019. Respiratory non-elective hospitalization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8057
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank tests based on the time to the first event are to compare the two treatment arms.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.26 to 2.83
	Estimation Comments	Hazard ratios and corresponding 95% CI are calculated by applying Cox-proportional hazard models.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020. All-cause non-elective hospitalization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4613
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank tests based on the time to the first event are to compare the two treatment arms.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 0.63 to 2.73
	Estimation Comments	Hazard ratios and corresponding 95% CI are calculated by applying Cox-proportional hazard models

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020. Respiratory non-elective hospitalization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9523
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank tests based on the time to the first event are to compare the two treatment arms.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.30 to 3.59
	Estimation Comments	Hazard ratios and corresponding 95% CI are calculated by applying Cox-proportional hazard models.

13. Secondary Outcome

Title	Percentage of Participants With Investigator-reported Acute Exacerbations
Description	Percentage of participants with acute exacerbation arereported.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	126
Measure Type: Number; Unit of Measure: Percentage of Participants
	3.9	5.6

14. Secondary Outcome

Title	Time to First Investigator-reported Acute Exacerbations
Description	Time to first investigator reported acute exacerbations from start of treatment are reported.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	126
Median (95% Confidence Interval); Unit of Measure: Weeks
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

The end point could not be analyzed due to the limited number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7871
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.26 to 2.78
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	126
Median (95% Confidence Interval); Unit of Measure: Week
	25.14 [1]; (24.14 to NA)	24.71 [1]; (24.14 to NA)

[1]

The end point could not be analyzed due to the limited number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3660
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank tests based on the time to the first event are to compare the two treatment arms.
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.56 to 1.24
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4173
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank tests based on the time to the first event are to compare the two treatment arms.
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.26
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	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.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	126
Median (95% Confidence Interval); Unit of Measure: Week
	NA [1]; (24.86 to NA)	NA [1]; (24.14 to NA)

[1]

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.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Primary Analysis in 2019
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2726
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank tests based on the time to the first event are to compare the two treatment arms.
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.20
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	Final Analysis in 2020
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3386
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank tests based on the time to the first event are to compare the two treatment arms.
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.24
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Time to Death From Any Cause
Description	Time to first documented death from start of treatment is reported.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	126
Median (95% Confidence Interval); Unit of Measure: Week
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

The end point could not be analyzed due to the limited number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9969
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank tests based on the time to the first event are to compare the two treatment arms.
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.06 to 16.08
	Estimation Comments	[Not Specified]

18. Secondary Outcome

Title	Time to Death From Respiratory Diseases
Description	Time to first documented death due to respiratory diseases from start of treatment will be reported.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	126
Median (95% Confidence Interval); Unit of Measure: Week
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

The end point could not be analyzed due to the limited number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3231
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank tests based on the time to the first event are to compare the two treatment arms.

19. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Baseline (Day 1) to Week 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	124
Measure Type: Number; Unit of Measure: Participants
	120	101

20. Secondary Outcome

Title	Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period
Description	Number of participants with dose reduction and treatment interruptions are reported.
Time Frame	From administration of the first dose of study drug to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	124
Measure Type: Number; Unit of Measure: Number of Participants
Participants with at least one dose modification	51	34
Participants with at least one dose interruption	40	12

21. Secondary Outcome

Title	Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up
Description	Number of participants with dose reduction and treatment interruptions are reported.
Time Frame	From the Follow-up Visit at Week 28 through the follow-up period of 12 Months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Open-Label Treatment (Pirfenidone)	Open-Label Treatment (Placebo)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	94	110
Measure Type: Number; Unit of Measure: Number of Participants
Participants with at least one dose modification	41	60
Participants with at least one dose interruption	24	34

22. Secondary Outcome

Title	Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the Double-Blind Period
Description	Number of participants withdrawn from trial treatment or trial discontinuations are reported.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	127	124
Measure Type: Number; Unit of Measure: Number of Participants
	25	12

23. Secondary Outcome

Title	Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the 12-month Safety Follow-up
Description	Number of participants withdrawn from trial treatment or trial discontinuations are reported.
Time Frame	From the Follow-up Visit at Week 28 through the follow-up period of 12 Months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Open-Label Treatment (Pirfenidone)	Open-Label Treatment (Placebo)
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	94	110
Measure Type: Number; Unit of Measure: Number of Participants
	19	26

Adverse Events

Time Frame	Baseline (Day 1) to Week 28 in the double-blind period From the Follow-up Visit at Week 28 through the follow-up period of 12 Months in the open-label treatment period
Adverse Event Reporting Description	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.
Arm/Group Title	Pirfenidone		Placebo		Open-Label Treatment (Pirfenidone)		Open-Label Treatment (Placebo)
Arm/Group Description	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.		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.		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.
All-Cause Mortality
	Pirfenidone		Placebo		Open-Label Treatment (Pirfenidone)		Open-Label Treatment (Placebo)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	4/127 (3.15%)		7/124 (5.65%)		7/94 (7.45%)		9/110 (8.18%)
Serious Adverse Events
	Pirfenidone		Placebo		Open-Label Treatment (Pirfenidone)		Open-Label Treatment (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/127 (14.17%)		20/124 (16.13%)		26/94 (27.66%)		27/110 (24.55%)
Cardiac disorders
Acute myocardial infarction † 1	0/127 (0.00%)	0	1/124 (0.81%)	1	1/94 (1.06%)	1	0/110 (0.00%)	0
Atrial fibrillation † 1	0/127 (0.00%)	0	1/124 (0.81%)	1	3/94 (3.19%)	3	0/110 (0.00%)	0
Cardiac failure † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	1/94 (1.06%)	1	1/110 (0.91%)	1
Cardiac failure congestive † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	2/94 (2.13%)	2	1/110 (0.91%)	1
Cardio-respiratory arrest † 1	0/127 (0.00%)	0	1/124 (0.81%)	1	1/94 (1.06%)	1	0/110 (0.00%)	0
Pericarditis † 1	0/127 (0.00%)	0	1/124 (0.81%)	1	0/94 (0.00%)	0	0/110 (0.00%)	0
Congenital, familial and genetic disorders
Atrial septal defect † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Eye disorders
Retinal detachment † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Gastrointestinal disorders
Ileus † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	2	0/110 (0.00%)	0
General disorders
General physical health deterioration † 1	0/127 (0.00%)	0	1/124 (0.81%)	1	0/94 (0.00%)	0	0/110 (0.00%)	0
Polyp † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	0/110 (0.00%)	0
Sudden death † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Hepatobiliary disorders
Hepatic function abnormal † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Immune system disorders
Lung transplant rejection † 1	0/127 (0.00%)	0	1/124 (0.81%)	1	0/94 (0.00%)	0	0/110 (0.00%)	0
Infections and infestations
Campylobacter gastroenteritis † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Gastroenteritis † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Influenza † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Lower respiratory tract infection † 1	1/127 (0.79%)	1	1/124 (0.81%)	1	1/94 (1.06%)	1	4/110 (3.64%)	6
Parainfluenzae virus infection † 1	0/127 (0.00%)	0	1/124 (0.81%)	1	0/94 (0.00%)	0	0/110 (0.00%)	0
Pneumonia † 1	1/127 (0.79%)	1	3/124 (2.42%)	3	2/94 (2.13%)	2	6/110 (5.45%)	6
Respiratory tract infection † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	2/94 (2.13%)	2	0/110 (0.00%)	0
Respiratory tract infection bacterial † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Urinary tract infection † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Urosepsis † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Atypical pneumonia † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	0/110 (0.00%)	0
Bronchitis † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Clostridium difficile colitis † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Device related infection † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Gastroenteritis viral † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	0/110 (0.00%)	0
Infective exacerbation of chronic obstructive airways disease † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	0/110 (0.00%)	0
Pneumonia influenzal † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Pneumonia viral † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	0/110 (0.00%)	0
Respiratory tract infection viral † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	0/110 (0.00%)	0
Toxocariasis † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	0/110 (0.00%)	0
Varicella zoster pneumonia † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Varicella zoster virus infection † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Viral infection † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	0/110 (0.00%)	0
Injury, poisoning and procedural complications
Procedural pain † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Spinal compression fracture † 1	0/127 (0.00%)	0	1/124 (0.81%)	1	0/94 (0.00%)	0	0/110 (0.00%)	0
Spinal fracture † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Wrist fracture † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	0/127 (0.00%)	0	1/124 (0.81%)	1	0/94 (0.00%)	0	0/110 (0.00%)	0
Influenza A virus test positive † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Metabolism and nutrition disorders
Decreased appetite † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Gout † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Hyponatraemia † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Arthritis † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Adenocarcinoma of colon † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Nervous system disorders
Cerebrovascular accident † 1	1/127 (0.79%)	1	1/124 (0.81%)	1	0/94 (0.00%)	0	2/110 (1.82%)	2
Loss of consciousness † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Presyncope † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Spinal cord compression † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	0/110 (0.00%)	0
Syncope † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	1/110 (0.91%)	1
Transient ischaemic attack † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	1/110 (0.91%)	1
Product Issues
Device occlusion † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	1
Renal and urinary disorders
Renal failure † 1	0/127 (0.00%)	0	1/124 (0.81%)	1	0/94 (0.00%)	0	0/110 (0.00%)	0
Nephrolithiasis † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	0/110 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease † 1	1/127 (0.79%)	2	0/124 (0.00%)	0	1/94 (1.06%)	2	0/110 (0.00%)	0
Cough † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Dyspnoea † 1	1/127 (0.79%)	1	2/124 (1.61%)	2	2/94 (2.13%)	3	3/110 (2.73%)	3
Interstitial lung disease † 1	2/127 (1.57%)	2	4/124 (3.23%)	4	5/94 (5.32%)	7	3/110 (2.73%)	4
Pulmonary embolism † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	2/94 (2.13%)	3	0/110 (0.00%)	0
Pulmonary fibrosis † 1	1/127 (0.79%)	1	1/124 (0.81%)	1	0/94 (0.00%)	0	2/110 (1.82%)	2
Respiratory disorder † 1	1/127 (0.79%)	1	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Hypercapnia † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	4
Pleuritic pain † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	2/94 (2.13%)	2	1/110 (0.91%)	1
Pneumothorax † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	0/94 (0.00%)	0	1/110 (0.91%)	3
Pulmonary oedema † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	2/94 (2.13%)	2	0/110 (0.00%)	0
Respiratory failure † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	2/94 (2.13%)	2	2/110 (1.82%)	3
1 Term from vocabulary, MedDRA 21.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pirfenidone		Placebo		Open-Label Treatment (Pirfenidone)		Open-Label Treatment (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	107/127 (84.25%)		81/124 (65.32%)		64/94 (68.09%)		86/110 (78.18%)
Gastrointestinal disorders
Constipation † 1	7/127 (5.51%)	7	4/124 (3.23%)	4	6/94 (6.38%)	6	3/110 (2.73%)	5
Diarrhoea † 1	23/127 (18.11%)	27	23/124 (18.55%)	24	9/94 (9.57%)	16	15/110 (13.64%)	15
Dyspepsia † 1	17/127 (13.39%)	21	7/124 (5.65%)	7	5/94 (5.32%)	5	8/110 (7.27%)	9
Gastrooesophageal reflux disease † 1	10/127 (7.87%)	10	6/124 (4.84%)	7	7/94 (7.45%)	8	7/110 (6.36%)	7
Nausea † 1	40/127 (31.50%)	49	9/124 (7.26%)	10	15/94 (15.96%)	18	30/110 (27.27%)	39
Vomiting † 1	14/127 (11.02%)	17	6/124 (4.84%)	7	4/94 (4.26%)	6	18/110 (16.36%)	25
Abdominal pain † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	2/94 (2.13%)	2	8/110 (7.27%)	8
Abdominal pain upper † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	10/110 (9.09%)	12
General disorders
Fatigue † 1	21/127 (16.54%)	22	19/124 (15.32%)	20	5/94 (5.32%)	5	12/110 (10.91%)	14
Pyrexia † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	1/94 (1.06%)	1	8/110 (7.27%)	9
Infections and infestations
Bronchitis † 1	10/127 (7.87%)	11	3/124 (2.42%)	3	0/94 (0.00%)	0	0/110 (0.00%)	0
Lower respiratory tract infection † 1	8/127 (6.30%)	10	13/124 (10.48%)	16	9/94 (9.57%)	12	14/110 (12.73%)	15
Nasopharyngitis † 1	7/127 (5.51%)	8	6/124 (4.84%)	9	10/94 (10.64%)	11	11/110 (10.00%)	11
Respiratory tract infection † 1	11/127 (8.66%)	11	5/124 (4.03%)	7	8/94 (8.51%)	9	9/110 (8.18%)	15
Upper respiratory tract infection † 1	12/127 (9.45%)	15	9/124 (7.26%)	10	10/94 (10.64%)	10	4/110 (3.64%)	5
Urinary tract infection † 1	0/127 (0.00%)	0	0/124 (0.00%)	0	7/94 (7.45%)	9	3/110 (2.73%)	3
Investigations
Weight decreased † 1	11/127 (8.66%)	11	6/124 (4.84%)	6	2/94 (2.13%)	2	7/110 (6.36%)	7
Metabolism and nutrition disorders
Decreased appetite † 1	18/127 (14.17%)	22	11/124 (8.87%)	11	7/94 (7.45%)	8	13/110 (11.82%)	13
Musculoskeletal and connective tissue disorders
Back pain † 1	8/127 (6.30%)	8	3/124 (2.42%)	3	0/94 (0.00%)	0	0/110 (0.00%)	0
Nervous system disorders
Dizziness † 1	11/127 (8.66%)	13	13/124 (10.48%)	14	4/94 (4.26%)	4	8/110 (7.27%)	8
Headache † 1	13/127 (10.24%)	19	4/124 (3.23%)	5	3/94 (3.19%)	3	12/110 (10.91%)	12
Psychiatric disorders
Depression † 1	7/127 (5.51%)	7	0/124 (0.00%)	0	0/94 (0.00%)	0	0/110 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	19/127 (14.96%)	21	16/124 (12.90%)	17	10/94 (10.64%)	12	9/110 (8.18%)	9
Dyspnoea † 1	14/127 (11.02%)	16	22/124 (17.74%)	25	9/94 (9.57%)	10	8/110 (7.27%)	8
Skin and subcutaneous tissue disorders
Photosensitivity reaction † 1	8/127 (6.30%)	9	0/124 (0.00%)	0	2/94 (2.13%)	2	9/110 (8.18%)	12
Rash † 1	9/127 (7.09%)	12	7/124 (5.65%)	8	8/94 (8.51%)	10	16/110 (14.55%)	19
1 Term from vocabulary, MedDRA 21.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800 821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Molina-Molina M, Kreuter M, Cottin V, Corte TJ, Gilberg F, Kirchgaessler KU, Axmann J, Maher TM. Efficacy of Pirfenidone vs. Placebo in Unclassifiable Interstitial Lung Disease, by Surgical Lung Biopsy Status: Data From a post-hoc Analysis. Front Med (Lausanne). 2022 Jun 17;9:897102. doi: 10.3389/fmed.2022.897102. eCollection 2022.

Kreuter M, Maher TM, Corte TJ, Molina-Molina M, Axmann J, Gilberg F, Kirchgaessler KU, Cottin V. Pirfenidone in Unclassifiable Interstitial Lung Disease: A Subgroup Analysis by Concomitant Mycophenolate Mofetil and/or Previous Corticosteroid Use. Adv Ther. 2022 Feb;39(2):1081-1095. doi: 10.1007/s12325-021-02009-w. Epub 2021 Dec 22.

Maher TM, Corte TJ, Fischer A, Kreuter M, Lederer DJ, Molina-Molina M, Axmann J, Kirchgaessler KU, Samara K, Gilberg F, Cottin V. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2020 Feb;8(2):147-157. doi: 10.1016/S2213-2600(19)30341-8. Epub 2019 Sep 29.

Graney BA, Fischer A. Interstitial Pneumonia with Autoimmune Features. Ann Am Thorac Soc. 2019 May;16(5):525-533. doi: 10.1513/AnnalsATS.201808-565CME.

Maher TM, Corte TJ, Fischer A, Kreuter M, Lederer DJ, Molina-Molina M, Axmann J, Kirchgaessler KU, Cottin V. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: design of a double-blind, randomised, placebo-controlled phase II trial. BMJ Open Respir Res. 2018 Sep 4;5(1):e000289. doi: 10.1136/bmjresp-2018-000289. eCollection 2018.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03099187
• Other Study ID Numbers: MA39189; 2016-002744-17 ( EudraCT Number )
• First Submitted: March 31, 2017
• First Posted: April 4, 2017
• Results First Submitted: November 14, 2019
• Results First Posted: January 3, 2020
• Last Update Posted: January 13, 2021