Trial Outcomes & Findings for Safety and Tolerability of Pirfenidone in Participants With Systemic Sclerosis-Related Interstitial Lung Disease (SSc-ILD) (LOTUSS) (NCT NCT01933334)

NCT ID: NCT01933334

Last Updated: 2016-08-04

Results Overview

Percentage of participants who had treatment-emergent AEs, defined as newly occurring or worsening after first dose. Relatedness to (study drug) was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

From baseline up to 28 days after the last dose of study drug (last dose = Week 16)

Results posted on

2016-08-04

Participant Flow

Participant milestones

Participant milestones
Measure	Pirfenidone: 2-Week Titration Group Participants received one 267 milligrams (mg) oral pirfenidone capsule three times daily (TID) (801 mg per day \[mg/day\]) for 1 week followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 1 week (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 14 weeks (maintenance period).	Pirfenidone: 4-Week Titration Group Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 2 weeks followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 2 weeks (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 12 weeks (maintenance period).
Overall Study STARTED	32	31
Overall Study COMPLETED	27	29
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Pirfenidone: 2-Week Titration Group Participants received one 267 milligrams (mg) oral pirfenidone capsule three times daily (TID) (801 mg per day \[mg/day\]) for 1 week followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 1 week (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 14 weeks (maintenance period).	Pirfenidone: 4-Week Titration Group Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 2 weeks followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 2 weeks (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 12 weeks (maintenance period).
Overall Study Adverse Event	5	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Safety and Tolerability of Pirfenidone in Participants With Systemic Sclerosis-Related Interstitial Lung Disease (SSc-ILD) (LOTUSS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pirfenidone: 2-Week Titration Group n=32 Participants Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 1 week followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 1 week (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 14 weeks (maintenance period).	Pirfenidone: 4-Week Titration Group n=31 Participants Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 2 weeks followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 2 weeks (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 12 weeks (maintenance period).	Total n=63 Participants Total of all reporting groups
Age, Continuous	49.3 years STANDARD_DEVIATION 12.08 • n=99 Participants	51.9 years STANDARD_DEVIATION 12.52 • n=107 Participants	50.6 years STANDARD_DEVIATION 12.27 • n=206 Participants
Sex: Female, Male Female	26 Participants n=99 Participants	26 Participants n=107 Participants	52 Participants n=206 Participants
Sex: Female, Male Male	6 Participants n=99 Participants	5 Participants n=107 Participants	11 Participants n=206 Participants

PRIMARY outcome

Timeframe: From baseline up to 28 days after the last dose of study drug (last dose = Week 16)

Population: Safety population included all randomized participants who provided written informed consent and received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Pirfenidone: 2-Week Titration Group n=32 Participants Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 1 week followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 1 week (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 14 weeks (maintenance period).	Pirfenidone: 4-Week Titration Group n=31 Participants Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 2 weeks followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 2 weeks (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 12 weeks (maintenance period).
Percentage of Participants With Treatment-Emergent Adverse Events (AEs)	96.9 percentage of participants	96.8 percentage of participants

PRIMARY outcome

Timeframe: From baseline up to 28 days after the last dose of study drug (last dose = Week 16)

Population: Safety population included all randomized participants who provided written informed consent and received at least one dose of study treatment.

An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Pirfenidone: 2-Week Titration Group n=32 Participants Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 1 week followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 1 week (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 14 weeks (maintenance period).	Pirfenidone: 4-Week Titration Group n=31 Participants Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 2 weeks followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 2 weeks (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 12 weeks (maintenance period).
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)	9.4 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, and 16

Population: Safety population. n = number of participants analyzed at specified time.

UCLA SCTC GIT Scale 2.0 is a 34-item self-administered questionnaire to obtain participant's assessment of the frequency of GI symptoms in preceding 7 days and how symptoms affected his/her life. All but 2 items were scored on a 0 to 3 scale (0=better health, 3=worse health); remaining 2 items were scored as 0 (better health) and 1 (worse health). The 34 items are divided into seven scales (reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being, and constipation). Individual scale score was calculated as the average of the items in the scale. Individual scale score ranged from 0 to 3 for reflux, distention/bloating, fecal soilage, social functioning, and emotional well-being; 0 to 2 for diarrhea; and 0 to 2.5 for constipation. A total score was also calculated as the average of 6 of the 7 scales (omitting constipation) and ranged from 0 to 2.83. For individual and total scores 0 indicated better health and higher score indicates worse health.

Outcome measures

Outcome measures
Measure	Pirfenidone: 2-Week Titration Group n=32 Participants Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 1 week followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 1 week (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 14 weeks (maintenance period).	Pirfenidone: 4-Week Titration Group n=31 Participants Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 2 weeks followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 2 weeks (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 12 weeks (maintenance period).
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Constipation: Week 4 (n=32, 30)	0.2656 units on a scale Standard Deviation 0.34159	0.1500 units on a scale Standard Deviation 0.29066
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Constipation: CFB Week 4 (n=32, 30)	0.0234 units on a scale Standard Deviation 0.42293	-0.0250 units on a scale Standard Deviation 0.30336
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Constipation: Week 8 (n=32, 31)	0.2578 units on a scale Standard Deviation 0.39901	0.1613 units on a scale Standard Deviation 0.46345
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Constipation: CFB Week 8 (n=32, 31)	0.0156 units on a scale Standard Deviation 0.25350	-0.0081 units on a scale Standard Deviation 0.38989
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Constipation: Week 12 (n=27, 30)	0.2407 units on a scale Standard Deviation 0.38904	0.2111 units on a scale Standard Deviation 0.36075
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Constipation: CFB Week 12 (n=27, 30)	0.0370 units on a scale Standard Deviation 0.37148	0.0528 units on a scale Standard Deviation 0.49008
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Constipation: Week 16 (n=25, 28)	0.1800 units on a scale Standard Deviation 0.29333	0.1518 units on a scale Standard Deviation 0.27504
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Constipation: CFB Week 16 (n=25, 28)	0.0200 units on a scale Standard Deviation 0.37444	-0.0179 units on a scale Standard Deviation 0.42453
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Total Score: Baseline (n=32, 31)	0.2194 units on a scale Standard Deviation 0.24262	0.2761 units on a scale Standard Deviation 0.32679
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Total Score: Week 4 (n=32, 31)	0.2845 units on a scale Standard Deviation 0.28528	0.2432 units on a scale Standard Deviation 0.31264
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Total Score: CFB Week 4 (n=32, 31)	0.0651 units on a scale Standard Deviation 0.20058	-0.0330 units on a scale Standard Deviation 0.13591
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Total Score: Week 8 (n=32, 31)	0.2759 units on a scale Standard Deviation 0.26133	0.2706 units on a scale Standard Deviation 0.29132
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Total Score: CFB Week 8 (n=32, 31)	0.0564 units on a scale Standard Deviation 0.15749	-0.0055 units on a scale Standard Deviation 0.20053
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Total Score: Week 12 (n=27, 30)	0.2416 units on a scale Standard Deviation 0.25329	0.2299 units on a scale Standard Deviation 0.27136
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Total Score: CFB Week 12 (n=27, 30)	0.0564 units on a scale Standard Deviation 0.16790	-0.0492 units on a scale Standard Deviation 0.17709
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Total Score: Week 16 (n=25, 28)	0.2237 units on a scale Standard Deviation 0.19767	0.2284 units on a scale Standard Deviation 0.26906
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Total Score: CFB Week 16 (n=25, 28)	0.0481 units on a scale Standard Deviation 0.14444	-0.0372 units on a scale Standard Deviation 0.20737
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Reflux: Baseline (n=32, 31)	0.3398 units on a scale Standard Deviation 0.34083	0.3347 units on a scale Standard Deviation 0.29117
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Reflux: Week 4 (n=32, 31)	0.4727 units on a scale Standard Deviation 0.43270	0.3548 units on a scale Standard Deviation 0.36529
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Reflux: CFB Week 4 (n=32, 31)	0.1328 units on a scale Standard Deviation 0.36469	0.0202 units on a scale Standard Deviation 0.26437
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Reflux: Week 8 (n=32, 31)	0.4660 units on a scale Standard Deviation 0.39881	0.4389 units on a scale Standard Deviation 0.46573
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Reflux: CFB Week 8 (n=32, 31)	0.1261 units on a scale Standard Deviation 0.36875	0.1043 units on a scale Standard Deviation 0.41664
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Reflux: Week 12 (n=27, 30)	0.4306 units on a scale Standard Deviation 0.41069	0.3417 units on a scale Standard Deviation 0.33142
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Reflux: CFB Week 12 (n=27, 30)	0.0880 units on a scale Standard Deviation 0.35494	0.0042 units on a scale Standard Deviation 0.26155
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Reflux: Week 16 (n=25, 28)	0.3950 units on a scale Standard Deviation 0.37270	0.3348 units on a scale Standard Deviation 0.39682
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Reflux: CFB Week 16 (n=25, 28)	0.0750 units on a scale Standard Deviation 0.25259	-0.0045 units on a scale Standard Deviation 0.31820
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Distention/Bloating: Baseline (n=32, 31)	0.3984 units on a scale Standard Deviation 0.57100	0.5968 units on a scale Standard Deviation 0.58693
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Distention/Bloating: Week 4 (n=32, 31)	0.6406 units on a scale Standard Deviation 0.65049	0.4919 units on a scale Standard Deviation 0.65346
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Distention/Bloating: CFB Week 4 (n=32, 31)	0.2422 units on a scale Standard Deviation 0.41874	-0.1048 units on a scale Standard Deviation 0.50734
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Distention/Bloating: Week 8 (n=32,31)	0.5703 units on a scale Standard Deviation 0.60985	0.4247 units on a scale Standard Deviation 0.57188
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Distention/Bloating: CFB Week 8 (n=32, 31)	0.1719 units on a scale Standard Deviation 0.47280	-0.1720 units on a scale Standard Deviation 0.43245
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Distention/Bloating: Week 12 (n=27, 30)	0.5370 units on a scale Standard Deviation 0.70610	0.4250 units on a scale Standard Deviation 0.56152
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Distention/Bloating: CFB Week 12 (n=27, 30)	0.2130 units on a scale Standard Deviation 0.59929	-0.1833 units on a scale Standard Deviation 0.47766
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Distention/Bloating: Week 16 (n=25, 28)	0.4800 units on a scale Standard Deviation 0.61627	0.4286 units on a scale Standard Deviation 0.48523
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Distention/Bloating: CFB Week 16 (n=25, 28)	0.1200 units on a scale Standard Deviation 0.45139	-0.1518 units on a scale Standard Deviation 0.45307
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Diarrhea: Baseline (n=32, 31)	0.3281 units on a scale Standard Deviation 0.48542	0.2742 units on a scale Standard Deviation 0.48026
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Diarrhea: Week 4 (n=32, 31)	0.3125 units on a scale Standard Deviation 0.48775	0.2258 units on a scale Standard Deviation 0.48026
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Diarrhea: CFB Week 4 (n=32, 31)	-0.0156 units on a scale Standard Deviation 0.57480	-0.0484 units on a scale Standard Deviation 0.43503
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Diarrhea: Week 8 (n=32, 31)	0.2813 units on a scale Standard Deviation 0.37968	0.3226 units on a scale Standard Deviation 0.55600
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Diarrhea: CFB Week 8 (n=32, 31)	-0.0469 units on a scale Standard Deviation 0.46419	0.0484 units on a scale Standard Deviation 0.58245
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Diarrhea: Week 12 (n=27, 30)	0.2778 units on a scale Standard Deviation 0.46685	0.2000 units on a scale Standard Deviation 0.48423
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Diarrhea: CFB Week 12 (n=27, 30)	-0.0556 units on a scale Standard Deviation 0.56045	-0.0667 units on a scale Standard Deviation 0.58329
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Diarrhea: Week 16 (n=25, 28)	0.3400 units on a scale Standard Deviation 0.51478	0.2500 units on a scale Standard Deviation 0.51819
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Diarrhea: CFB Week 16 (n=25, 28)	0.0400 units on a scale Standard Deviation 0.57591	-0.0179 units on a scale Standard Deviation 0.61587
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Social Functioning: Baseline (n=32, 31)	0.1250 units on a scale Standard Deviation 0.28078	0.1893 units on a scale Standard Deviation 0.43585
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Social Functioning: Week 4 (n=32, 31)	0.1563 units on a scale Standard Deviation 0.26072	0.1775 units on a scale Standard Deviation 0.27199
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Social Functioning: CFB Week 4 (n=32, 31)	0.0313 units on a scale Standard Deviation 0.25893	-0.0118 units on a scale Standard Deviation 0.28143
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Social Functioning: Week 8 (n=32, 31)	0.1886 units on a scale Standard Deviation 0.31322	0.1936 units on a scale Standard Deviation 0.33647
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Social Functioning: CFB Week 8 (n=32, 31)	0.0635 units on a scale Standard Deviation 0.29233	0.0044 units on a scale Standard Deviation 0.37997
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Social Functioning: Week 12 (n=27, 30)	0.1173 units on a scale Standard Deviation 0.23488	0.1944 units on a scale Standard Deviation 0.30028
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Social Functioning: CFB Week 12 (n=27, 30)	0.0432 units on a scale Standard Deviation 0.25154	-0.0011 units on a scale Standard Deviation 0.35730
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Social Functioning: Week 16 (n=25, 28)	0.0600 units on a scale Standard Deviation 0.13502	0.1667 units on a scale Standard Deviation 0.27596
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Social Functioning: CFB Week 16 (n=25, 28)	0.0133 units on a scale Standard Deviation 0.16607	-0.0131 units on a scale Standard Deviation 0.40515
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Emotional Wellbeing: Baseline (n=32, 31)	0.0937 units on a scale Standard Deviation 0.26033	0.1326 units on a scale Standard Deviation 0.41910
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Emotional Wellbeing: Week 4 (n=32, 30)	0.0937 units on a scale Standard Deviation 0.21697	0.0778 units on a scale Standard Deviation 0.32516
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Emotional Wellbeing: CFB Week 4 (n=32, 30)	0.0000 units on a scale Standard Deviation 0.17831	-0.0593 units on a scale Standard Deviation 0.14808
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Emotional Wellbeing: Week 8 (n=32, 31)	0.1181 units on a scale Standard Deviation 0.33273	0.0825 units on a scale Standard Deviation 0.29680
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Emotional Wellbeing: CFB Week 8 (n=32, 31)	0.0243 units on a scale Standard Deviation 0.11887	-0.0502 units on a scale Standard Deviation 0.19846
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Emotional Wellbeing: Week 12 (n=27, 30)	0.0493 units on a scale Standard Deviation 0.13182	0.0852 units on a scale Standard Deviation 0.30979
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Emotional Wellbeing: CFB Week 12 (n=27, 30)	0.0123 units on a scale Standard Deviation 0.12055	-0.0482 units on a scale Standard Deviation 0.14786
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Emotional Wellbeing: Week 16 (n=25, 28)	0.0266 units on a scale Standard Deviation 0.08030	0.0833 units on a scale Standard Deviation 0.39959
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Emotional Wellbeing: CFB Week 16 (n=25, 28)	0.0000 units on a scale Standard Deviation 0.10627	-0.0357 units on a scale Standard Deviation 0.12851
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Fecal Soilage: Baseline (n=32, 31)	0.0313 units on a scale Standard Deviation 0.17678	0.1290 units on a scale Standard Deviation 0.42755
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Fecal Soilage: Week 4 (n=32, 31)	0.0313 units on a scale Standard Deviation 0.17678	0.1290 units on a scale Standard Deviation 0.42755
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Fecal Soilage: CFB Week 4 (n=32, 31)	0.0000 units on a scale Standard Deviation 0.00000	0.0000 units on a scale Standard Deviation 0.00000
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Fecal Soilage: Week 8 (n=32, 31)	0.0313 units on a scale Standard Deviation 0.17678	0.1613 units on a scale Standard Deviation 0.45437
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Fecal Soilage: CFB Week 8 (n=32, 31)	0.0000 units on a scale Standard Deviation 0.00000	0.0323 units on a scale Standard Deviation 0.17961
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Fecal Soilage: Week 12 (n=27, 30)	0.0370 units on a scale Standard Deviation 0.19245	0.1333 units on a scale Standard Deviation 0.43417
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Fecal Soilage: CFB Week 12 (n=27, 30)	0.0370 units on a scale Standard Deviation 0.19245	0.0000 units on a scale Standard Deviation 0.00000
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Fecal Soilage: Week 16 (n=25, 28)	0.0400 units on a scale Standard Deviation 0.20000	0.1071 units on a scale Standard Deviation 0.41627
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Fecal Soilage: CFB Week 16 (n=25, 28)	0.0400 units on a scale Standard Deviation 0.20000	0.0000 units on a scale Standard Deviation 0.00000
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores Constipation: Baseline (n=32, 31)	0.2422 units on a scale Standard Deviation 0.40899	0.1694 units on a scale Standard Deviation 0.26130

Adverse Events

Pirfenidone: 2-Week Titration Group

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

Pirfenidone: 4-Week Titration Group

Serious events: 0 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pirfenidone: 2-Week Titration Group n=32 participants at risk Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 1 week followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 1 week (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 14 weeks (maintenance period).	Pirfenidone: 4-Week Titration Group n=31 participants at risk Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 2 weeks followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 2 weeks (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 12 weeks (maintenance period).
Infections and infestations Bronchitis	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Small intestinal obstruction	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)

Other adverse events

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Pirfenidone: 2-Week Titration Group n=32 participants at risk Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 1 week followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 1 week (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 14 weeks (maintenance period).	Pirfenidone: 4-Week Titration Group n=31 participants at risk Participants received one 267 mg oral pirfenidone capsule TID (801 mg/day) for 2 weeks followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 2 weeks (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 12 weeks (maintenance period).
Cardiac disorders Palpitations	9.4% 3/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Abdominal distension	12.5% 4/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Abdominal pain	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Abdominal pain upper	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Constipation	15.6% 5/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Diarrhoea	28.1% 9/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	32.3% 10/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Dry mouth	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Dyspepsia	12.5% 4/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	12.9% 4/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Flatulence	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	3.2% 1/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Gastrooesophageal reflux disease	18.8% 6/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	22.6% 7/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Nausea	50.0% 16/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	48.4% 15/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Stomach discomfort	9.4% 3/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	12.9% 4/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Gastrointestinal disorders Vomiting	28.1% 9/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	29.0% 9/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
General disorders Asthenia	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	16.1% 5/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
General disorders Chest discomfort	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
General disorders Chills	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
General disorders Fatigue	40.6% 13/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	32.3% 10/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
General disorders Oedema peripheral	9.4% 3/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	3.2% 1/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
General disorders Pyrexia	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Infections and infestations Gastroenteritis viral	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Infections and infestations Influenza	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	9.7% 3/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Infections and infestations Nasopharyngitis	9.4% 3/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Infections and infestations Pneumonia	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Infections and infestations Sinusitis	0.00% 0/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Infections and infestations Upper respiratory tract infection	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	9.7% 3/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Infections and infestations Urinary tract infection	0.00% 0/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Injury, poisoning and procedural complications Fall	0.00% 0/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	9.7% 3/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Investigations Weight decreased	9.4% 3/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	3.2% 1/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Metabolism and nutrition disorders Anorexia	15.6% 5/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Metabolism and nutrition disorders Decreased appetite	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Musculoskeletal and connective tissue disorders Arthralgia	15.6% 5/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	12.9% 4/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Musculoskeletal and connective tissue disorders Back pain	15.6% 5/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	9.7% 3/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Musculoskeletal and connective tissue disorders Joint swelling	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Musculoskeletal and connective tissue disorders Muscle spasms	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Musculoskeletal and connective tissue disorders Pain in extremity	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Nervous system disorders Dizziness	15.6% 5/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	16.1% 5/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Nervous system disorders Headache	43.8% 14/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	45.2% 14/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Nervous system disorders Hypoaesthesia	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	3.2% 1/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Psychiatric disorders Insomnia	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	16.1% 5/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Respiratory, thoracic and mediastinal disorders Cough	31.2% 10/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	12.9% 4/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Respiratory, thoracic and mediastinal disorders Dysphonia	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.4% 3/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	12.9% 4/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Skin and subcutaneous tissue disorders Erythema	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Skin and subcutaneous tissue disorders Photosensitivity reaction	6.2% 2/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Skin and subcutaneous tissue disorders Pruritus	12.5% 4/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	12.9% 4/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Skin and subcutaneous tissue disorders Rash	25.0% 8/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	16.1% 5/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Vascular disorders Hot flush	3.1% 1/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	6.5% 2/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Vascular disorders Hypotension	9.4% 3/32 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	0.00% 0/31 • From baseline up to 28 days after the last dose of study drug (last dose = Week 16)