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Trial record 2 of 4 for:    esbriet | scleroderma

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01933334
Recruitment Status : Completed
First Posted : September 2, 2013
Results First Posted : September 28, 2015
Last Update Posted : August 4, 2016
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Systemic Sclerosis
Intervention Drug: Pirfenidone
Enrollment 63
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pirfenidone: 2-Week Titration Group Pirfenidone: 4-Week Titration Group
Hide Arm/Group Description 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). 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).
Period Title: Overall Study
Started 32 31
Completed 27 29
Not Completed 5 2
Reason Not Completed
Adverse Event             5             1
Withdrawal by Subject             0             1
Arm/Group Title Pirfenidone: 2-Week Titration Group Pirfenidone: 4-Week Titration Group Total
Hide Arm/Group Description 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). 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 of all reporting groups
Overall Number of Baseline Participants 32 31 63
Hide Baseline Analysis Population Description
Safety population included all randomized participants who provided written informed consent and received at least one dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 31 participants 63 participants
49.3  (12.08) 51.9  (12.52) 50.6  (12.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 31 participants 63 participants
Female
26
  81.3%
26
  83.9%
52
  82.5%
Male
6
  18.8%
5
  16.1%
11
  17.5%
1.Primary Outcome
Title Percentage of Participants With Treatment-Emergent Adverse Events (AEs)
Hide Description 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.
Time Frame From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who provided written informed consent and received at least one dose of study treatment.
Arm/Group Title Pirfenidone: 2-Week Titration Group Pirfenidone: 4-Week Titration Group
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 32 31
Measure Type: Number
Unit of Measure: percentage of participants
96.9 96.8
2.Primary Outcome
Title Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
Hide Description 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.
Time Frame From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who provided written informed consent and received at least one dose of study treatment.
Arm/Group Title Pirfenidone: 2-Week Titration Group Pirfenidone: 4-Week Titration Group
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 32 31
Measure Type: Number
Unit of Measure: percentage of participants
9.4 0.0
3.Secondary Outcome
Title University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores
Hide Description 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.
Time Frame Baseline, Weeks 4, 8, 12, and 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. n = number of participants analyzed at specified time.
Arm/Group Title Pirfenidone: 2-Week Titration Group Pirfenidone: 4-Week Titration Group
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 32 31
Mean (Standard Deviation)
Unit of Measure: units on a scale
Reflux: Baseline (n=32, 31) 0.3398  (0.34083) 0.3347  (0.29117)
Reflux: Week 4 (n=32, 31) 0.4727  (0.43270) 0.3548  (0.36529)
Reflux: CFB Week 4 (n=32, 31) 0.1328  (0.36469) 0.0202  (0.26437)
Reflux: Week 8 (n=32, 31) 0.4660  (0.39881) 0.4389  (0.46573)
Reflux: CFB Week 8 (n=32, 31) 0.1261  (0.36875) 0.1043  (0.41664)
Reflux: Week 12 (n=27, 30) 0.4306  (0.41069) 0.3417  (0.33142)
Reflux: CFB Week 12 (n=27, 30) 0.0880  (0.35494) 0.0042  (0.26155)
Reflux: Week 16 (n=25, 28) 0.3950  (0.37270) 0.3348  (0.39682)
Reflux: CFB Week 16 (n=25, 28) 0.0750  (0.25259) -0.0045  (0.31820)
Distention/Bloating: Baseline (n=32, 31) 0.3984  (0.57100) 0.5968  (0.58693)
Distention/Bloating: Week 4 (n=32, 31) 0.6406  (0.65049) 0.4919  (0.65346)
Distention/Bloating: CFB Week 4 (n=32, 31) 0.2422  (0.41874) -0.1048  (0.50734)
Distention/Bloating: Week 8 (n=32,31) 0.5703  (0.60985) 0.4247  (0.57188)
Distention/Bloating: CFB Week 8 (n=32, 31) 0.1719  (0.47280) -0.1720  (0.43245)
Distention/Bloating: Week 12 (n=27, 30) 0.5370  (0.70610) 0.4250  (0.56152)
Distention/Bloating: CFB Week 12 (n=27, 30) 0.2130  (0.59929) -0.1833  (0.47766)
Distention/Bloating: Week 16 (n=25, 28) 0.4800  (0.61627) 0.4286  (0.48523)
Distention/Bloating: CFB Week 16 (n=25, 28) 0.1200  (0.45139) -0.1518  (0.45307)
Diarrhea: Baseline (n=32, 31) 0.3281  (0.48542) 0.2742  (0.48026)
Diarrhea: Week 4 (n=32, 31) 0.3125  (0.48775) 0.2258  (0.48026)
Diarrhea: CFB Week 4 (n=32, 31) -0.0156  (0.57480) -0.0484  (0.43503)
Diarrhea: Week 8 (n=32, 31) 0.2813  (0.37968) 0.3226  (0.55600)
Diarrhea: CFB Week 8 (n=32, 31) -0.0469  (0.46419) 0.0484  (0.58245)
Diarrhea: Week 12 (n=27, 30) 0.2778  (0.46685) 0.2000  (0.48423)
Diarrhea: CFB Week 12 (n=27, 30) -0.0556  (0.56045) -0.0667  (0.58329)
Diarrhea: Week 16 (n=25, 28) 0.3400  (0.51478) 0.2500  (0.51819)
Diarrhea: CFB Week 16 (n=25, 28) 0.0400  (0.57591) -0.0179  (0.61587)
Social Functioning: Baseline (n=32, 31) 0.1250  (0.28078) 0.1893  (0.43585)
Social Functioning: Week 4 (n=32, 31) 0.1563  (0.26072) 0.1775  (0.27199)
Social Functioning: CFB Week 4 (n=32, 31) 0.0313  (0.25893) -0.0118  (0.28143)
Social Functioning: Week 8 (n=32, 31) 0.1886  (0.31322) 0.1936  (0.33647)
Social Functioning: CFB Week 8 (n=32, 31) 0.0635  (0.29233) 0.0044  (0.37997)
Social Functioning: Week 12 (n=27, 30) 0.1173  (0.23488) 0.1944  (0.30028)
Social Functioning: CFB Week 12 (n=27, 30) 0.0432  (0.25154) -0.0011  (0.35730)
Social Functioning: Week 16 (n=25, 28) 0.0600  (0.13502) 0.1667  (0.27596)
Social Functioning: CFB Week 16 (n=25, 28) 0.0133  (0.16607) -0.0131  (0.40515)
Emotional Wellbeing: Baseline (n=32, 31) 0.0937  (0.26033) 0.1326  (0.41910)
Emotional Wellbeing: Week 4 (n=32, 30) 0.0937  (0.21697) 0.0778  (0.32516)
Emotional Wellbeing: CFB Week 4 (n=32, 30) 0.0000  (0.17831) -0.0593  (0.14808)
Emotional Wellbeing: Week 8 (n=32, 31) 0.1181  (0.33273) 0.0825  (0.29680)
Emotional Wellbeing: CFB Week 8 (n=32, 31) 0.0243  (0.11887) -0.0502  (0.19846)
Emotional Wellbeing: Week 12 (n=27, 30) 0.0493  (0.13182) 0.0852  (0.30979)
Emotional Wellbeing: CFB Week 12 (n=27, 30) 0.0123  (0.12055) -0.0482  (0.14786)
Emotional Wellbeing: Week 16 (n=25, 28) 0.0266  (0.08030) 0.0833  (0.39959)
Emotional Wellbeing: CFB Week 16 (n=25, 28) 0.0000  (0.10627) -0.0357  (0.12851)
Fecal Soilage: Baseline (n=32, 31) 0.0313  (0.17678) 0.1290  (0.42755)
Fecal Soilage: Week 4 (n=32, 31) 0.0313  (0.17678) 0.1290  (0.42755)
Fecal Soilage: CFB Week 4 (n=32, 31) 0.0000  (0.00000) 0.0000  (0.00000)
Fecal Soilage: Week 8 (n=32, 31) 0.0313  (0.17678) 0.1613  (0.45437)
Fecal Soilage: CFB Week 8 (n=32, 31) 0.0000  (0.00000) 0.0323  (0.17961)
Fecal Soilage: Week 12 (n=27, 30) 0.0370  (0.19245) 0.1333  (0.43417)
Fecal Soilage: CFB Week 12 (n=27, 30) 0.0370  (0.19245) 0.0000  (0.00000)
Fecal Soilage: Week 16 (n=25, 28) 0.0400  (0.20000) 0.1071  (0.41627)
Fecal Soilage: CFB Week 16 (n=25, 28) 0.0400  (0.20000) 0.0000  (0.00000)
Constipation: Baseline (n=32, 31) 0.2422  (0.40899) 0.1694  (0.26130)
Constipation: Week 4 (n=32, 30) 0.2656  (0.34159) 0.1500  (0.29066)
Constipation: CFB Week 4 (n=32, 30) 0.0234  (0.42293) -0.0250  (0.30336)
Constipation: Week 8 (n=32, 31) 0.2578  (0.39901) 0.1613  (0.46345)
Constipation: CFB Week 8 (n=32, 31) 0.0156  (0.25350) -0.0081  (0.38989)
Constipation: Week 12 (n=27, 30) 0.2407  (0.38904) 0.2111  (0.36075)
Constipation: CFB Week 12 (n=27, 30) 0.0370  (0.37148) 0.0528  (0.49008)
Constipation: Week 16 (n=25, 28) 0.1800  (0.29333) 0.1518  (0.27504)
Constipation: CFB Week 16 (n=25, 28) 0.0200  (0.37444) -0.0179  (0.42453)
Total Score: Baseline (n=32, 31) 0.2194  (0.24262) 0.2761  (0.32679)
Total Score: Week 4 (n=32, 31) 0.2845  (0.28528) 0.2432  (0.31264)
Total Score: CFB Week 4 (n=32, 31) 0.0651  (0.20058) -0.0330  (0.13591)
Total Score: Week 8 (n=32, 31) 0.2759  (0.26133) 0.2706  (0.29132)
Total Score: CFB Week 8 (n=32, 31) 0.0564  (0.15749) -0.0055  (0.20053)
Total Score: Week 12 (n=27, 30) 0.2416  (0.25329) 0.2299  (0.27136)
Total Score: CFB Week 12 (n=27, 30) 0.0564  (0.16790) -0.0492  (0.17709)
Total Score: Week 16 (n=25, 28) 0.2237  (0.19767) 0.2284  (0.26906)
Total Score: CFB Week 16 (n=25, 28) 0.0481  (0.14444) -0.0372  (0.20737)
Time Frame From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pirfenidone: 2-Week Titration Group Pirfenidone: 4-Week Titration Group
Hide Arm/Group Description 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). 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).
All-Cause Mortality
Pirfenidone: 2-Week Titration Group Pirfenidone: 4-Week Titration Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pirfenidone: 2-Week Titration Group Pirfenidone: 4-Week Titration Group
Affected / at Risk (%) Affected / at Risk (%)
Total   3/32 (9.38%)   0/31 (0.00%) 
Gastrointestinal disorders     
Small intestinal obstruction * 1  1/32 (3.13%)  0/31 (0.00%) 
Infections and infestations     
Bronchitis * 1  1/32 (3.13%)  0/31 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Interstitial lung disease * 1  1/32 (3.13%)  0/31 (0.00%) 
Pulmonary hypertension * 1  1/32 (3.13%)  0/31 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pirfenidone: 2-Week Titration Group Pirfenidone: 4-Week Titration Group
Affected / at Risk (%) Affected / at Risk (%)
Total   31/32 (96.88%)   30/31 (96.77%) 
Cardiac disorders     
Palpitations * 1  3/32 (9.38%)  2/31 (6.45%) 
Gastrointestinal disorders     
Abdominal distension * 1  4/32 (12.50%)  2/31 (6.45%) 
Abdominal pain * 1  1/32 (3.13%)  2/31 (6.45%) 
Abdominal pain upper * 1  1/32 (3.13%)  2/31 (6.45%) 
Constipation * 1  5/32 (15.63%)  2/31 (6.45%) 
Diarrhoea * 1  9/32 (28.13%)  10/31 (32.26%) 
Dry mouth * 1  2/32 (6.25%)  0/31 (0.00%) 
Dyspepsia * 1  4/32 (12.50%)  4/31 (12.90%) 
Flatulence * 1  2/32 (6.25%)  1/31 (3.23%) 
Gastrooesophageal reflux disease * 1  6/32 (18.75%)  7/31 (22.58%) 
Nausea * 1  16/32 (50.00%)  15/31 (48.39%) 
Stomach discomfort * 1  3/32 (9.38%)  4/31 (12.90%) 
Vomiting * 1  9/32 (28.13%)  9/31 (29.03%) 
General disorders     
Asthenia * 1  2/32 (6.25%)  5/31 (16.13%) 
Chest discomfort * 1  2/32 (6.25%)  0/31 (0.00%) 
Chills * 1  2/32 (6.25%)  0/31 (0.00%) 
Fatigue * 1  13/32 (40.63%)  10/31 (32.26%) 
Oedema peripheral * 1  3/32 (9.38%)  1/31 (3.23%) 
Pyrexia * 1  2/32 (6.25%)  0/31 (0.00%) 
Infections and infestations     
Gastroenteritis viral * 1  2/32 (6.25%)  0/31 (0.00%) 
Influenza * 1  1/32 (3.13%)  3/31 (9.68%) 
Nasopharyngitis * 1  3/32 (9.38%)  2/31 (6.45%) 
Pneumonia * 1  2/32 (6.25%)  0/31 (0.00%) 
Sinusitis * 1  0/32 (0.00%)  2/31 (6.45%) 
Upper respiratory tract infection * 1  1/32 (3.13%)  3/31 (9.68%) 
Urinary tract infection * 1  0/32 (0.00%)  2/31 (6.45%) 
Injury, poisoning and procedural complications     
Fall * 1  0/32 (0.00%)  3/31 (9.68%) 
Investigations     
Weight decreased * 1  3/32 (9.38%)  1/31 (3.23%) 
Metabolism and nutrition disorders     
Anorexia * 1  5/32 (15.63%)  2/31 (6.45%) 
Decreased appetite * 1  1/32 (3.13%)  2/31 (6.45%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  5/32 (15.63%)  4/31 (12.90%) 
Back pain * 1  5/32 (15.63%)  3/31 (9.68%) 
Joint swelling * 1  2/32 (6.25%)  0/31 (0.00%) 
Muscle spasms * 1  1/32 (3.13%)  2/31 (6.45%) 
Musculoskeletal pain * 1  0/32 (0.00%)  2/31 (6.45%) 
Myalgia * 1  0/32 (0.00%)  2/31 (6.45%) 
Pain in extremity * 1  1/32 (3.13%)  2/31 (6.45%) 
Nervous system disorders     
Dizziness * 1  5/32 (15.63%)  5/31 (16.13%) 
Headache * 1  14/32 (43.75%)  14/31 (45.16%) 
Hypoaesthesia * 1  2/32 (6.25%)  1/31 (3.23%) 
Psychiatric disorders     
Insomnia * 1  2/32 (6.25%)  5/31 (16.13%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  10/32 (31.25%)  4/31 (12.90%) 
Dysphonia * 1  1/32 (3.13%)  2/31 (6.45%) 
Dyspnoea * 1  3/32 (9.38%)  4/31 (12.90%) 
Skin and subcutaneous tissue disorders     
Erythema * 1  1/32 (3.13%)  2/31 (6.45%) 
Photosensitivity reaction * 1  2/32 (6.25%)  2/31 (6.45%) 
Pruritus * 1  4/32 (12.50%)  4/31 (12.90%) 
Rash * 1  8/32 (25.00%)  5/31 (16.13%) 
Vascular disorders     
Hot flush * 1  1/32 (3.13%)  2/31 (6.45%) 
Hypotension * 1  3/32 (9.38%)  0/31 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01933334     History of Changes
Other Study ID Numbers: PSSc-001
First Submitted: August 23, 2013
First Posted: September 2, 2013
Results First Submitted: August 25, 2015
Results First Posted: September 28, 2015
Last Update Posted: August 4, 2016