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Safety Study of Oral Pirfenidone in Patients With Pulmonary Fibrosis/Idiopathic Pulmonary Fibrosis

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ClinicalTrials.gov Identifier: NCT00080223
Recruitment Status : Completed
First Posted : March 26, 2004
Results First Posted : March 9, 2016
Last Update Posted : April 17, 2017
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Conditions Idiopathic Pulmonary Fibrosis
Pulmonary Fibrosis
Intervention Drug: Pirfenidone
Enrollment 83
Recruitment Details  
Pre-assignment Details Participants could enroll from Study PIPF-001 (a double-blind comparison of pirfenidone and prednisone in pulmonary fibrosis); individual-patient protocols (IPPs); investigator-sponsored Investigational New Drug applications (INDs) in idiopathic pulmonary fibrosis (IPF); and via an early access program (EAP) for participants with IPF.
Arm/Group Title Pirfenidone
Hide Arm/Group Description Pirfenidone was administered orally, in divided doses, three times daily at a maximum dose of up to 3600 milligram per day (mg/d). At the start of treatment in this study, doses for participants with no previous pirfenidone exposure and for those who took their last dose greater than (>) 4 weeks before enrollment were titrated to their maintenance dose based on body weight and tolerability. Dose titration was also required after a dosing interruption of >28 days. Pirfenidone was administered for a maximum duration of 604 weeks in this study.
Period Title: Overall Study
Started 83
Completed 7
Not Completed 76
Reason Not Completed
Adverse Event             23
Death             21
Withdrawal by Subject             13
Lung Transplantation             9
Non-compliance With Study Treatment             7
Participant unwilling to continue             2
Physician Decision             1
Arm/Group Title Pirfenidone
Hide Arm/Group Description Pirfenidone was administered orally, in divided doses, three times daily at a maximum dose of up to 3600 mg/d. At the start of treatment in this study, doses for participants with no previous pirfenidone exposure and for those who took their last dose >4 weeks before enrollment were titrated to their maintenance dose based on body weight and tolerability. Dose titration was also required after a dosing interruption of >28 days. Pirfenidone was administered for a maximum duration of 604 weeks in this study.
Overall Number of Baseline Participants 83
Hide Baseline Analysis Population Description
All treated participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 83 participants
68.5  (9.15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants
Female
23
  27.7%
Male
60
  72.3%
1.Primary Outcome
Title Percentage of Participants With a Treatment-Emergent Adverse Event (AE), Serious AE (SAE), Severe AE, Life-threatening AE, Death or Discontinuation Because of an AE
Hide Description An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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. AEs were classified as severe (Grade 3) in following cases: marked limitation in activity; some assistance usually required; medical intervention/ therapy required, hospitalization possible. Treatment-emergent AEs were those occurring on or after the first dosing day and up to 28 days after discontinuation of study treatment, and those occurring before treatment that worsened after the first study dose. AE included serious as well as non-serious AEs.
Time Frame Baseline to 28 days after the last dose of study treatment (maximum duration of treatment in study was 604 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Pirfenidone
Hide Arm/Group Description:
Pirfenidone was administered orally, in divided doses, three times daily at a maximum dose of up to 3600 mg/d. At the start of treatment in this study, doses for participants with no previous pirfenidone exposure and for those who took their last dose >4 weeks before enrollment were titrated to their maintenance dose based on body weight and tolerability. Dose titration was also required after a dosing interruption of >28 days. Pirfenidone was administered for a maximum duration of 604 weeks in this study.
Overall Number of Participants Analyzed 83
Measure Type: Number
Unit of Measure: percentage of participants
Any AE 98.8
SAE 59.0
Severe AE 36.1
Life-threatening AE 21.7
AEs leading to death 25.3
AE leading to study treatment discontinuation 43.4
2.Secondary Outcome
Title Percent Predicted Forced Vital Capacity (FVC)
Hide Description FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out from the lungs after full inspiration in the upright position, measured in liters. Predicted FVC is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (actual FVC value in liter)/(predicted FVC) * 100%
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants. "n" = participants who were evaluable for specified time point.
Arm/Group Title Pirfenidone
Hide Arm/Group Description:
Pirfenidone was administered orally, in divided doses, three times daily at a maximum dose of up to 3600 mg/d. At the start of treatment in this study, doses for participants with no previous pirfenidone exposure and for those who took their last dose >4 weeks before enrollment were titrated to their maintenance dose based on body weight and tolerability. Dose titration was also required after a dosing interruption of >28 days. Pirfenidone was administered for a maximum duration of 604 weeks in this study.
Overall Number of Participants Analyzed 83
Mean (Standard Deviation)
Unit of Measure: percent predicted FVC
Baseline (n=78) 67.7  (18.70)
Week 24 (n=71) 67.5  (17.11)
Week 48 (n=57) 68.7  (17.36)
Week 72 (n=50) 68.4  (16.20)
Week 96 (n=47) 67.9  (17.76)
Week 120 (n=44) 67.7  (18.03)
Week 144 (n=39) 66.1  (18.22)
Week 168 (n=35) 65.7  (17.74)
Week 192 (n=28) 67.8  (18.32)
Week 216 (n=28) 68.7  (21.97)
Week 240 (n=22) 65.3  (16.80)
Week 264 (n=15) 70.1  (13.26)
Week 288 (n=14) 76.6  (18.71)
Week 312 (n=14) 71.1  (14.03)
Week 336 (n=10) 64.9  (13.61)
Week 360 (n=7) 60.9  (15.00)
Week 384 (n=6) 68.4  (17.43)
Week 408 (n=4) 65.1  (11.84)
Week 432 (n=1) 61.5 [1]   (NA)
Week 456 (n=1) 78.4 [1]   (NA)
Week 480 (n=1) 80.9 [1]   (NA)
[1]
Standard deviation was not available as there was only 1 participant analyzed for this time point.
3.Secondary Outcome
Title Hemoglobin (Hgb)-Corrected Percent-Predicted Carbon Monoxide Diffusing Capacity (DLco)
Hide Description DLco is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. Predicted DLco is based on a formula using sex, age and height of a person. Predicted DLco = [Hbg-corrected DLco value (in milliliters per minute per millimeter mercury [mL/min/mmHg])/predicted DLco] * 100%
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants. "n" = participants who were evaluable for specified time point.
Arm/Group Title Pirfenidone
Hide Arm/Group Description:
Pirfenidone was administered orally, in divided doses, three times daily at a maximum dose of up to 3600 mg/d. At the start of treatment in this study, doses for participants with no previous pirfenidone exposure and for those who took their last dose >4 weeks before enrollment were titrated to their maintenance dose based on body weight and tolerability. Dose titration was also required after a dosing interruption of >28 days. Pirfenidone was administered for a maximum duration of 604 weeks in this study.
Overall Number of Participants Analyzed 83
Mean (Standard Deviation)
Unit of Measure: percent predicted DLco
Baseline (n=74) 38.0  (13.36)
Week 24 (n=65) 39.5  (13.56)
Week 48 (n=55) 37.1  (13.55)
Week 72 (n=49) 37.0  (12.01)
Week 96 (n=44) 38.0  (12.35)
Week 120 (n=41) 35.7  (12.55)
Week 144 (n=37) 38.5  (13.47)
Week 168 (n=33) 36.7  (12.98)
Week 192 (n=27) 37.2  (11.34)
Week 216 (n=28) 35.8  (11.31)
Week 240 (n=22) 35.5  (12.67)
Week 264 (n=15) 37.5  (9.69)
Week 288 (n=14) 42.9  (18.43)
Week 312 (n=14) 38.6  (9.54)
Week 336 (n=10) 33.7  (6.41)
Week 360 (n=7) 37.1  (11.19)
Week 384 (n=5) 38.3  (13.16)
Week 408 (n=4) 38.1  (9.41)
Week 432 (n=1) 33.9 [1]   (NA)
Week 456 (n=1) 11.6 [1]   (NA)
Week 480 (n=1) 38.9 [1]   (NA)
[1]
Standard deviation was not available as there was only 1 participant analyzed for this time point.
4.Secondary Outcome
Title Resting Oxygen Saturation by Pulse Oximetry (SpO2)
Hide Description SpO2 is the percentage of oxygen saturation in the blood. Oxygen level (oxygen saturation) of the blood was measured using pulse oximetry on room air.
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants. "n" = participants who were evaluable for specified time point.
Arm/Group Title Pirfenidone
Hide Arm/Group Description:
Pirfenidone was administered orally, in divided doses, three times daily at a maximum dose of up to 3600 mg/d. At the start of treatment in this study, doses for participants with no previous pirfenidone exposure and for those who took their last dose >4 weeks before enrollment were titrated to their maintenance dose based on body weight and tolerability. Dose titration was also required after a dosing interruption of >28 days. Pirfenidone was administered for a maximum duration of 604 weeks in this study.
Overall Number of Participants Analyzed 83
Mean (Standard Deviation)
Unit of Measure: percentage of oxygen saturation
Baseline (n=72) 94.5  (3.53)
Week 24 (n=55) 94.4  (4.14)
Week 48 (n=47) 94.8  (3.05)
Week 72 (n=41) 94.9  (3.01)
Week 96 (n=36) 94.9  (2.77)
Week 120 (n=35) 94.8  (2.46)
Week 144 (n=33) 94.8  (2.78)
Week 168 (n=25) 94.0  (3.18)
Week 192 (n=22) 94.9  (2.59)
Week 216 (n=23) 95.2  (2.33)
Week 240 (n=17) 95.5  (2.67)
Week 264 (n=11) 95.7  (1.56)
Week 288 (n=10) 94.6  (4.09)
Week 312 (n=11) 95.8  (2.48)
Week 336 (n=9) 94.4  (2.35)
Week 360 (n=7) 94.9  (4.02)
Week 384 (n=7) 94.0  (2.77)
Week 408 (n=6) 94.8  (2.86)
Week 432 (n=1) 95.0 [1]   (NA)
Week 456 (n=1) 97.0 [1]   (NA)
Week 480 (n=3) 95.0  (2.00)
[1]
Standard deviation was not available as there was only 1 participant analyzed for this time point.
5.Secondary Outcome
Title Overall Survival
Hide Description Survival was analyzed as time from first study dose to death (all-cause mortality) with surviving participants censored at their last available assessment.
Time Frame First dosing of study treatment until death (up to 604 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Pirfenidone
Hide Arm/Group Description:
Pirfenidone was administered orally, in divided doses, three times daily at a maximum dose of up to 3600 mg/d. At the start of treatment in this study, doses for participants with no previous pirfenidone exposure and for those who took their last dose >4 weeks before enrollment were titrated to their maintenance dose based on body weight and tolerability. Dose titration was also required after a dosing interruption of >28 days. Pirfenidone was administered for a maximum duration of 604 weeks in this study.
Overall Number of Participants Analyzed 83
Median (95% Confidence Interval)
Unit of Measure: weeks
508.7 [1] 
(264.14 to NA)
[1]
The upper limit of the 95% confidence interval was not calculable because of higher (>50%) number of censored participants.
Time Frame Baseline to 28 days after the last dose of study treatment (maximum duration of treatment in study was 604 weeks)
Adverse Event Reporting Description All treated participants
 
Arm/Group Title Pirfenidone
Hide Arm/Group Description Pirfenidone was administered orally, in divided doses, three times daily at a maximum dose of up to 3600 mg/d. At the start of treatment in this study, doses for participants with no previous pirfenidone exposure and for those who took their last dose >4 weeks before enrollment were titrated to their maintenance dose based on body weight and tolerability. Dose titration was also required after a dosing interruption of >28 days. Pirfenidone was administered for a maximum duration of 604 weeks in this study.
All-Cause Mortality
Pirfenidone
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Pirfenidone
Affected / at Risk (%)
Total   49/83 (59.04%) 
Blood and lymphatic system disorders   
Anaemia * 1  1/83 (1.20%) 
Cardiac disorders   
Acute myocardial infarction * 1  1/83 (1.20%) 
Angina pectoris * 1  1/83 (1.20%) 
Atrial fibrillation * 1  4/83 (4.82%) 
Atrial flutter * 1  1/83 (1.20%) 
Cardiac arrest * 1  1/83 (1.20%) 
Cardiac failure congestive * 1  2/83 (2.41%) 
Coronary artery disease * 1  3/83 (3.61%) 
Coronary artery occlusion * 1  1/83 (1.20%) 
Myocardial infarction * 1  2/83 (2.41%) 
Supraventricular tachycardia * 1  1/83 (1.20%) 
Ventricular fibrillation * 1  1/83 (1.20%) 
Gastrointestinal disorders   
Abdominal hernia * 1  1/83 (1.20%) 
Abdominal strangulated hernia * 1  1/83 (1.20%) 
Colitis ischaemic * 1  2/83 (2.41%) 
Diverticulum * 1  1/83 (1.20%) 
Nausea * 1  1/83 (1.20%) 
Oesophageal disorder * 1  1/83 (1.20%) 
General disorders   
Non-cardiac chest pain * 1  1/83 (1.20%) 
Infections and infestations   
Bronchitis * 1  3/83 (3.61%) 
Device related infection * 1  1/83 (1.20%) 
Gastroenteritis * 1  1/83 (1.20%) 
Influenza * 1  1/83 (1.20%) 
Lobar pneumonia * 1  1/83 (1.20%) 
Pneumonia * 1  9/83 (10.84%) 
Respiratory tract infection * 1  1/83 (1.20%) 
Sepsis * 1  1/83 (1.20%) 
Viral infection * 1  1/83 (1.20%) 
Injury, poisoning and procedural complications   
Chest injury * 1  1/83 (1.20%) 
Facial bones fracture * 1  1/83 (1.20%) 
Fall * 1  1/83 (1.20%) 
Hip fracture * 1  1/83 (1.20%) 
Humerus fracture * 1  1/83 (1.20%) 
Limb injury * 1  1/83 (1.20%) 
Pelvic fracture * 1  1/83 (1.20%) 
Radius fracture * 1  1/83 (1.20%) 
Ulna fracture * 1  1/83 (1.20%) 
Metabolism and nutrition disorders   
Hyponatraemia * 1  1/83 (1.20%) 
Starvation * 1  1/83 (1.20%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast cancer * 1  1/83 (1.20%) 
Lung squamous cell carcinoma stage unspecified * 1  2/83 (2.41%) 
Metastases to lymph nodes * 1  1/83 (1.20%) 
Metastatic neoplasm * 1  1/83 (1.20%) 
Non-small cell lung cancer * 1  1/83 (1.20%) 
Nervous system disorders   
Autonomic nervous system imbalance * 1  1/83 (1.20%) 
Cerebrovascular accident * 1  2/83 (2.41%) 
Dementia * 1  1/83 (1.20%) 
Encephalopathy * 1  1/83 (1.20%) 
Syncope * 1  1/83 (1.20%) 
Renal and urinary disorders   
Renal failure acute * 1  1/83 (1.20%) 
Reproductive system and breast disorders   
Benign prostatic hyperplasia * 1  1/83 (1.20%) 
Respiratory, thoracic and mediastinal disorders   
Acute respiratory failure * 1  1/83 (1.20%) 
Asthma * 1  1/83 (1.20%) 
Bronchospasm * 1  1/83 (1.20%) 
Chronic respiratory failure * 1  1/83 (1.20%) 
Dyspnoea * 1  4/83 (4.82%) 
Hypoxia * 1  1/83 (1.20%) 
Idiopathic pulmonary fibrosis * 1  15/83 (18.07%) 
Interstitial lung disease * 1  1/83 (1.20%) 
Pneumothorax * 1  2/83 (2.41%) 
Pulmonary alveolar haemorrhage * 1  1/83 (1.20%) 
Pulmonary embolism * 1  1/83 (1.20%) 
Respiratory arrest * 1  1/83 (1.20%) 
Respiratory failure * 1  6/83 (7.23%) 
Vascular disorders   
Shock * 1  1/83 (1.20%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pirfenidone
Affected / at Risk (%)
Total   81/83 (97.59%) 
Blood and lymphatic system disorders   
Anaemia * 1  5/83 (6.02%) 
Gastrointestinal disorders   
Abdominal discomfort * 1  7/83 (8.43%) 
Constipation * 1  10/83 (12.05%) 
Diarrhoea * 1  10/83 (12.05%) 
Dyspepsia * 1  7/83 (8.43%) 
Gastrooesophageal reflux disease * 1  10/83 (12.05%) 
Nausea * 1  40/83 (48.19%) 
Stomach discomfort * 1  5/83 (6.02%) 
Vomiting * 1  13/83 (15.66%) 
General disorders   
Asthenia * 1  8/83 (9.64%) 
Fatigue * 1  27/83 (32.53%) 
Oedema peripheral * 1  9/83 (10.84%) 
Pyrexia * 1  7/83 (8.43%) 
Infections and infestations   
Bronchitis * 1  12/83 (14.46%) 
Nasopharyngitis * 1  8/83 (9.64%) 
Respiratory tract infection * 1  6/83 (7.23%) 
Sinusitis * 1  11/83 (13.25%) 
Upper respiratory tract infection * 1  21/83 (25.30%) 
Urinary tract infection * 1  11/83 (13.25%) 
Injury, poisoning and procedural complications   
Contusion * 1  6/83 (7.23%) 
Skin laceration * 1  6/83 (7.23%) 
Investigations   
Weight decreased * 1  18/83 (21.69%) 
Metabolism and nutrition disorders   
Anorexia * 1  11/83 (13.25%) 
Decreased appetite * 1  14/83 (16.87%) 
Musculoskeletal and connective tissue disorders   
Back pain * 1  10/83 (12.05%) 
Myalgia * 1  6/83 (7.23%) 
Nervous system disorders   
Dizziness * 1  12/83 (14.46%) 
Headache * 1  14/83 (16.87%) 
Psychiatric disorders   
Anxiety * 1  10/83 (12.05%) 
Depression * 1  12/83 (14.46%) 
Insomnia * 1  15/83 (18.07%) 
Renal and urinary disorders   
Proteinuria * 1  5/83 (6.02%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  21/83 (25.30%) 
Dyspnoea * 1  23/83 (27.71%) 
Idiopathic pulmonary fibrosis * 1  21/83 (25.30%) 
Nasal congestion * 1  8/83 (9.64%) 
Pulmonary hypertension * 1  10/83 (12.05%) 
Skin and subcutaneous tissue disorders   
Photosensitivity reaction * 1  6/83 (7.23%) 
Pruritus * 1  5/83 (6.02%) 
Rash * 1  16/83 (19.28%) 
Vascular disorders   
Hypertension * 1  8/83 (9.64%) 
*
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-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00080223    
Other Study ID Numbers: PIPF-002
GA29989 ( Other Identifier: Hoffmann-La Roche )
First Submitted: March 24, 2004
First Posted: March 26, 2004
Results First Submitted: February 10, 2016
Results First Posted: March 9, 2016
Last Update Posted: April 17, 2017