Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00287729
• Collaborator: (none)
• Enrollment: 344
• Location: 1
• Arms: 2
• Duration (Months): 31
• Patients Per Site Per Month: 11.1

Study Details

Study Description

Brief Summary

The purposes of this study are to assess the efficacy of treatment with pirfenidone 2403 milligrams per day compared with placebo in patients with idiopathic pulmonary fibrosis (IPF)and to assess the safety of treatment with pirfenidone 2403 milligrams per day compared with placebo in patients with idiopathic pulmonary fibrosis.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Pirfenidone; Drug: Placebo	Phase 3

Detailed Description

This is a Phase 3, randomized, double-blind, placebo-controlled, safety and efficacy study of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF). Approximately 320 patients at approximately 50 centers will be randomly assigned (1:1) to receive pirfenidone 2403 milligrams or placebo equivalent administered in divided doses three times per day (TID) with food. The primary outcome variable will be the absolute change in percent predicted Forced Vital Capacity from Baseline to Week 72. Patients will be randomized by geographic region.

Patients will receive blinded study treatment from the time of randomization until the last patient randomized has been treated for 72 weeks. A Data Monitoring Committee (DMC) will periodically review safety and efficacy data to ensure patient safety.

After week 72, patients who meet the Progression of Disease (POD) definition, which is a ≥ 10% absolute decrease in percent predicted Forced Vital Capacity or a ≥ 15% absolute decrease in percent predicted carbon monoxide diffusing capacity (DLco), will be eligible to receive permitted idiopathic pulmonary fibrosis therapies in addition to their blinded study drug. Permitted idiopathic pulmonary therapies include corticosteroids, azathioprine, cyclophosphamide and N-acetyl-cysteine (with restrictions).

Study Design

• Study Type: Interventional
• Actual Enrollment: 344 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo Controlled, Phase 3 Study of the Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 2403 mg/day pirfenidone 2403 mg/day pirfenidone dose group.	Drug: Pirfenidone; 2403 mg/day given orally, and administered in divided doses three times daily with food, for the duration of the study.
Placebo Comparator: placebo Placebo equivalent.	Drug: Placebo; Placebo equivalent, given orally, and administered in divided doses three times daily with food, for the duration of the study.

Outcome Measures

Primary Outcome Measures

1. Absolute Change in Percent Predicted Forced Vital Capacity(FVC) [Baseline to week 72]

   Mean Change in Percent Predicted Forced Vital Capacity (FVC) as measured from baseline to week 72. It is calculated as the simple difference between baseline Percent Predicted FVC measurements and week 72 Percent Predicted FVC measurements.

Secondary Outcome Measures

1. Categorical Assessment of Absolute Change in Percent Predicted Forced Vital Capacity [Baseline to week 72]

   Based on the change in baseline percent predicted FVC at week 72, patients were assigned to 1 of 5 categories: mild decline (<10% but >=0% decline), moderate decline (<20% but >=10% decline), severe decline (>=20% decline), mild improvement (>0% but <10% improvement), or moderate improvement (>=10% improvement). Those who died or had a lung transplant before Week 72 were included in the severe decline category. The results indicate the number of patients who experience Categorical Change in Percent Predicted Forced Vital Capacity.

2. Progression-free Survival [Baseline to Week 72]

   Progression is defined as the first occurrence of a 10% absolute decline from baseline in percent predicted Forced Vital Capacity, a 15% absolute decline from baseline in percent predicted hemoglobin(Hgb)-corrected carbon monoxide diffusing capacity (DLco), or, death.

3. Change in the Six-Minute Walk Test (6MWT) Distance [Baseline to Week 72]

   The change from Baseline to week 72 in distance walked during the 6-Minute Walk Test. This measure was calculated as the simple difference between baseline distanced walked over 6 minutes and week 72 distance walked over 6 minutes as measured in meters (m).

4. Change in Worst Oxygen Saturation by Pulse Oximetry (SpO2) Measurement Observed During the 6-Minute Walk Test [Baseline to Week 72]

   The change from baseline to week 72 in worst oxygen saturation during the 6-Minute Walk Test as measure by Pulse Oximetry (SpO2) Level. It is calculated as the simple difference between baseline SpO2 measurements and week 72 SpO2 measurements.

5. Change in Percent Predicted Hemoglobin (Hb)-Corrected Carbon Monoxide Diffusing Capacity (DLco) of the Lungs [Baseline to Week 72]

   The change from baseline to week 72 in Percent Predicted Hemoglobin (Hb)-Corrected Carbon Monoxide Diffusing Capacity (DLco) of the Lungs. It is calculated as the simple difference between baseline DLco measurements and week 72 DLco measurements.

6. Change in Dyspnea Score [Baseline to Week 72]

   The mean change from baseline to week 72 in Dyspnea score was measured by the University of San Diego Shortness of Breath Questionnaire (UCSD SOBQ). The SOBQ is used to assess shortness of breath with various activities of daily living (for example, brushing ones teeth or mowing the lawn). Patients rated the severity of their shortness of breath experienced on an average day during the past week on a 6 point scale (0 to 5),with 0= not at all breathless, 4= severely breathless and 5= Maximally or unable to do because of breathlessness.

7. Worsening of IPF [Time to acute IPF exacerbation, IPF-related death, lung transplant or respiratory hospitalization, whichever comes first.]

   Worsening of IPF was defined by the occurrence of any of the following events: Acute IPF exacerbation, IPF-related death, Lung transplantation, or Respiratory hospitalization.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Primary Inclusion criteria:

• diagnosis of idiopathic pulmonary fibrosis

• 40 to 80 years of age

• Forced Vital Capacity ≥ 50% predicted value

• carbon monoxide diffusing capacity (DLco) ≥ 35% predicted value

• either Forced Vital Capacity or carbon monoxide diffusing capacity (DLco) ≤ 90% predicted value

• no improvement in past year

• able to walk 150 meters in 6 minutes and maintain saturation ≥ 83% while on no more than 6 liters per minute supplemental oxygen

Primary Exclusion criteria:

• unable to undergo pulmonary function testing

• evidence of significant obstructive lung disease or airway hyper-responsiveness

• in the clinical opinion of the investigator, the patient is expected to need and be eligible for a lung transplant within 72 weeks of randomization

• active infection

• liver disease

• cancer or other medical condition likely to result in death within 2 years

• diabetes

• pregnancy or lactation

• substance abuse

• personal or family history of long QT syndrome

• other IPF treatment

• unable to take study medication

• withdrawal from other IPF trials

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	InterMune, Inc.	Brisbane	California	United States	94005

Sponsors and Collaborators

• Genentech, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT00287729
• Other Study ID Numbers: PIPF-006; Capacity 1
• First Posted: Feb 7, 2006
• Last Update Posted: Apr 17, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Genentech, Inc.: Idiopathic; Pulmonary; Fibrosis; Lung; Pirfenidone; InterMune
• Additional relevant MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pirfenidone

Study Results

Participant Flow

Arm/Group Title	Pirfenidone (2403 mg/d)	Placebo
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day	placebo equivalent, given as 3 divided doses 3 times/day
Period Title: Overall Study
STARTED	171	173
COMPLETED	137	142
NOT COMPLETED	34	31

Baseline Characteristics

Arm/Group Title	Pirfenidone (2403 mg/d)	Placebo	Total
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day	placebo equivalent, given as 3 divided doses 3 times/day	Total of all reporting groups
Overall Participants	171	173	344
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	70 40.9%	61 35.3%	131 38.1%
>=65 years	101 59.1%	112 64.7%	213 61.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.8 (7.90)	67.0 (7.80)	66.9 (7.84)
Sex: Female, Male (Count of Participants)
Female	48 28.1%	49 28.3%	97 28.2%
Male	123 71.9%	124 71.7%	247 71.8%
Region of Enrollment (participants) [Number]
United States	148 86.5%	150 86.7%	298 86.6%
Europe	23 13.5%	22 12.7%	45 13.1%
Australia	0 0%	1 0.6%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Absolute Change in Percent Predicted Forced Vital Capacity(FVC)
Description	Mean Change in Percent Predicted Forced Vital Capacity (FVC) as measured from baseline to week 72. It is calculated as the simple difference between baseline Percent Predicted FVC measurements and week 72 Percent Predicted FVC measurements.
Time Frame	Baseline to week 72

Outcome Measure Data

Analysis Population Description

A modified intent-to-treat population of all randomized patients who received any amount of study drug is the primary population for efficacy and safety analyses. Missing FVC data due to death were assigned the worst rank and missing FVC data due to reasons other than death were imputed using the SSD method.

Arm/Group Title	Pirfenidone (2403 mg/d)	Placebo
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day	placebo equivalent, given as 3 divided doses 3 times/day
Measure Participants	171	173
Mean (Standard Deviation) [Change in Percent Predicted FVC]	-9 (19.58)	-10 (19.12)

2. Secondary Outcome

Title	Categorical Assessment of Absolute Change in Percent Predicted Forced Vital Capacity
Description	Based on the change in baseline percent predicted FVC at week 72, patients were assigned to 1 of 5 categories: mild decline (<10% but >=0% decline), moderate decline (<20% but >=10% decline), severe decline (>=20% decline), mild improvement (>0% but <10% improvement), or moderate improvement (>=10% improvement). Those who died or had a lung transplant before Week 72 were included in the severe decline category. The results indicate the number of patients who experience Categorical Change in Percent Predicted Forced Vital Capacity.
Time Frame	Baseline to week 72

Outcome Measure Data

Analysis Population Description

A modified intent-to-treat population of all randomized patients who received any amount of study drug is used as the primary population for all efficacy and safety analyses. Missing data were imputed by the SSD method if the patient was alive and imputed to 0% if the patient died before the protocol-specified time point.

Arm/Group Title	Pirfenidone (2403 mg/d)	Placebo
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day	placebo equivalent, given as 3 divided doses 3 times/day
Measure Participants	171	173
Decline >=20% or death or lung transplantation	20	23
Decline <20% but >= 10%	19	23
Decline <10% but > 0%	88	89
Improvement of >=0% but <10%	41	33
Improvement of >=10%	3	5

3. Secondary Outcome

Title	Progression-free Survival
Description	Progression is defined as the first occurrence of a 10% absolute decline from baseline in percent predicted Forced Vital Capacity, a 15% absolute decline from baseline in percent predicted hemoglobin(Hgb)-corrected carbon monoxide diffusing capacity (DLco), or, death.
Time Frame	Baseline to Week 72

Outcome Measure Data

Analysis Population Description

A modified intent-to-treat population of all randomized patients who received any amount of study drug is used as the primary population for efficacy and safety analyses.

Arm/Group Title	Pirfenidone (2403 mg/d)	Placebo
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day	placebo equivalent, given as 3 divided doses 3 times/day
Measure Participants	171	173
Death or Disease Progression	54	60
Decline in percent predicted FVC >=10%	31	41
Decline in percent predicted DLco >=15%	10	9
Death Before Disease Progression	13	10

4. Secondary Outcome

Title	Change in the Six-Minute Walk Test (6MWT) Distance
Description	The change from Baseline to week 72 in distance walked during the 6-Minute Walk Test. This measure was calculated as the simple difference between baseline distanced walked over 6 minutes and week 72 distance walked over 6 minutes as measured in meters (m).
Time Frame	Baseline to Week 72

Outcome Measure Data

Analysis Population Description

A modified intent-to-treat population of all randomized patients who received any amount of study drug is used as the primary population for efficacy and safety analyses. Missing data were imputed by the SSD method if the patient was alive and imputed to 0 meters if the patient had died before the protocol-specified time point.

Arm/Group Title	Pirfenidone (2403 mg/d)	Placebo
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day	placebo equivalent, given as 3 divided doses 3 times/day
Measure Participants	171	173
Mean (Standard Deviation) [Change in Distance Walked in Meters]	-45 (140)	-77 (128)

5. Secondary Outcome

Title	Change in Worst Oxygen Saturation by Pulse Oximetry (SpO2) Measurement Observed During the 6-Minute Walk Test
Description	The change from baseline to week 72 in worst oxygen saturation during the 6-Minute Walk Test as measure by Pulse Oximetry (SpO2) Level. It is calculated as the simple difference between baseline SpO2 measurements and week 72 SpO2 measurements.
Time Frame	Baseline to Week 72

Outcome Measure Data

Analysis Population Description

A modified intent-to-treat population of all randomized patients who received any amount of study drug is used as the primary population for efficacy and safety analyses. Missing data were imputed by the SSD method if the patient was alive and imputed to 83% if the patient died before the protocol-specified time point.

Arm/Group Title	Pirfenidone (2403 mg/d)	Placebo
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day	placebo equivalent, given as 3 divided doses 3 times/day
Measure Participants	171	173
Mean (Standard Deviation) [Change,Worst Oxygen Saturation (Percent)]	-1.9 (3.83)	-1.3 (6.63)

6. Secondary Outcome

Title	Change in Percent Predicted Hemoglobin (Hb)-Corrected Carbon Monoxide Diffusing Capacity (DLco) of the Lungs
Description	The change from baseline to week 72 in Percent Predicted Hemoglobin (Hb)-Corrected Carbon Monoxide Diffusing Capacity (DLco) of the Lungs. It is calculated as the simple difference between baseline DLco measurements and week 72 DLco measurements.
Time Frame	Baseline to Week 72

Outcome Measure Data

Analysis Population Description

A modified intent-to-treat population of all randomized patients who received any amount of study drug is used as the primary population for efficacy and safety analyses. Missing data were imputed by the SSD method if the patient was alive and imputed to 0% if the patient died before the protocol-specified time point.

Arm/Group Title	Pirfenidone (2403 mg/d)	Placebo
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day	placebo equivalent, given as 3 divided doses 3 times/day
Measure Participants	171	173
Mean (Standard Deviation) [Change in Percent Predicted DLco]	-9.8 (12.61)	-9.2 (13.24)

7. Secondary Outcome

Title	Change in Dyspnea Score
Description	The mean change from baseline to week 72 in Dyspnea score was measured by the University of San Diego Shortness of Breath Questionnaire (UCSD SOBQ). The SOBQ is used to assess shortness of breath with various activities of daily living (for example, brushing ones teeth or mowing the lawn). Patients rated the severity of their shortness of breath experienced on an average day during the past week on a 6 point scale (0 to 5),with 0= not at all breathless, 4= severely breathless and 5= Maximally or unable to do because of breathlessness.
Time Frame	Baseline to Week 72

Outcome Measure Data

Analysis Population Description

A modified intent-to-treat population of all randomized patients who received any amount of study drug is used as the primary population for efficacy and safety analyses. Missing data were imputed by the SSD method if the patient was alive and imputed to a score of 120 if the patient died before the protocol-specified time point.

Arm/Group Title	Pirfenidone (2403 mg/d)	Placebo
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day	placebo equivalent, given as 3 divided doses 3 times/day
Measure Participants	171	173
Mean (Standard Deviation) [Change in Dyspnea Score]	11.9 (24.72)	13.9 (27.89)

8. Secondary Outcome

Title	Worsening of IPF
Description	Worsening of IPF was defined by the occurrence of any of the following events: Acute IPF exacerbation, IPF-related death, Lung transplantation, or Respiratory hospitalization.
Time Frame	Time to acute IPF exacerbation, IPF-related death, lung transplant or respiratory hospitalization, whichever comes first.

Outcome Measure Data

Analysis Population Description

A modified intent-to-treat population of all randomized patients who received any amount of study drug is used as the primary population for efficacy and safety analyses.

Arm/Group Title	Pirfenidone (2403 mg/d)	Placebo
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day	placebo equivalent, given as 3 divided doses 3 times/day
Measure Participants	171	173
Woresening IPF	24	32
Acute IPF exacerbation	2	1
IPF-related death	3	6
Lung transplantation	2	2
Respiratory hospitalization	17	23
Patients Censored	146	141

Adverse Events

Arm/Group Title	Pirfenidone (2403 mg/d)		Placebo
Arm/Group Description	pirfenidone, total daily dose of 2403 mg/day, given as 3 divided doses 3 times/day		placebo equivalent, given as 3 divided doses 3 times/day
All Cause Mortality
	Pirfenidone (2403 mg/d)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pirfenidone (2403 mg/d)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/171 (31%)		51/173 (29.5%)
Cardiac disorders
Angina Pectoris	1/171 (0.6%)		1/173 (0.6%)
Angina Unstable	0/171 (0%)		1/173 (0.6%)
Atrial Fibrillation	2/171 (1.2%)		1/173 (0.6%)
Cardiac Failure Congestive	1/171 (0.6%)		1/173 (0.6%)
Coronary Artery Disease	6/171 (3.5%)		0/173 (0%)
Coronary Artery Stenosis	0/171 (0%)		1/173 (0.6%)
Myocardial Infarction	1/171 (0.6%)		0/173 (0%)
Sick Sinus Syndrome	2/171 (1.2%)		0/173 (0%)
Supraventricular Tachycardia	1/171 (0.6%)		0/173 (0%)
Ventricular Tachycardia	1/171 (0.6%)		0/173 (0%)
Gastrointestinal disorders
Colitis	2/171 (1.2%)		0/173 (0%)
Diverticular Perforation	1/171 (0.6%)		1/173 (0.6%)
Ileus	0/171 (0%)		1/173 (0.6%)
Pancreatitis	1/171 (0.6%)		0/173 (0%)
General disorders
Asthenia	0/171 (0%)		1/173 (0.6%)
Chest Pain	1/171 (0.6%)		0/173 (0%)
Multi Organ Failure	1/171 (0.6%)		0/173 (0%)
Non-Cardiac Chest Pain	0/171 (0%)		1/173 (0.6%)
Pyrexia	1/171 (0.6%)		0/173 (0%)
Hepatobiliary disorders
Cholelithiasis	1/171 (0.6%)		0/173 (0%)
Hepatitis	1/171 (0.6%)		0/173 (0%)
Infections and infestations
Abdominal Abscess	0/171 (0%)		1/173 (0.6%)
Bronchiectasis	0/171 (0%)		1/173 (0.6%)
Bronchitis	0/171 (0%)		5/173 (2.9%)
Bronchitis Viral	1/171 (0.6%)		0/173 (0%)
Cholecystitis Infective	1/171 (0.6%)		0/173 (0%)
Chronic Sinusitis	1/171 (0.6%)		0/173 (0%)
Clostridium Difficile Colitis	0/171 (0%)		1/173 (0.6%)
Diverticulitis	0/171 (0%)		1/173 (0.6%)
Lobar Pneumonia	7/171 (4.1%)		7/173 (4%)
Pneumonia	1/171 (0.6%)		0/173 (0%)
Respiratory Tract Infection	1/171 (0.6%)		0/173 (0%)
Septic Shock	1/171 (0.6%)		0/173 (0%)
Sinusitis	0/171 (0%)		1/173 (0.6%)
Urinary Tract Infection	1/171 (0.6%)		1/173 (0.6%)
Viral Infection	0/171 (0%)		1/173 (0.6%)
Viral Upper Respiratory Tract Infection	1/171 (0.6%)		0/173 (0%)
Injury, poisoning and procedural complications
Ankle Fracture	1/171 (0.6%)		0/173 (0%)
Concussion	0/171 (0%)		1/173 (0.6%)
Endotracheal Intubation Complication	1/171 (0.6%)		0/173 (0%)
Fall	2/171 (1.2%)		1/173 (0.6%)
Femur Fracture	1/171 (0.6%)		0/173 (0%)
Hip Fracture	2/171 (1.2%)		0/173 (0%)
Psychosis Postoperative	1/171 (0.6%)		0/173 (0%)
Radius Fracture	1/171 (0.6%)		0/173 (0%)
Spinal Compression Fracture	1/171 (0.6%)		0/173 (0%)
Investigations
Hepatic Enzyme Increased	0/171 (0%)		1/173 (0.6%)
Liver Function Test Abnormal	2/171 (1.2%)		0/173 (0%)
Weight Decreased	0/171 (0%)		1/173 (0.6%)
Metabolism and nutrition disorders
Pelvic Fracture	1/171 (0.6%)		0/173 (0%)
Dehydration	1/171 (0.6%)		0/173 (0%)
Diabetes Mellitus Inadequate Control	0/171 (0%)		1/173 (0.6%)
Hyperkalaemia	1/171 (0.6%)		0/173 (0%)
Hypoglycaemia	1/171 (0.6%)		0/173 (0%)
Hyponatraemia	1/171 (0.6%)		0/173 (0%)
Musculoskeletal and connective tissue disorders
Bursitis	1/171 (0.6%)		0/173 (0%)
Intervertebral Disc Protrusion	2/171 (1.2%)		0/173 (0%)
Myalgia	1/171 (0.6%)		0/173 (0%)
Osteoarthritis	0/171 (0%)		1/173 (0.6%)
Pathological Fracture	0/171 (0%)		1/173 (0.6%)
Rotator Cuff Syndrome	0/171 (0%)		1/173 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Cancer	1/171 (0.6%)		1/173 (0.6%)
Bladder Transitional Cell Carcinoma	0/171 (0%)		1/173 (0.6%)
Breast Cancer	0/171 (0%)		1/173 (0.6%)
Colon Cancer Stage II	1/171 (0.6%)		0/173 (0%)
Metastases to Bone	1/171 (0.6%)		0/173 (0%)
Metastases to Lung	1/171 (0.6%)		0/173 (0%)
Metastastic Neoplasm	0/171 (0%)		1/173 (0.6%)
Metastatic Squamous Cell Carcinoma	0/171 (0%)		1/173 (0.6%)
Ovarian Cancer	0/171 (0%)		1/173 (0.6%)
Pancreatic Carcinoma	1/171 (0.6%)		0/173 (0%)
Prostate Cancer	2/171 (1.2%)		0/173 (0%)
Small Cell Lung Cancer Stage Unspecified	1/171 (0.6%)		1/173 (0.6%)
Squamous Cell Carcinoma	0/171 (0%)		1/173 (0.6%)
Transitional Cell Carcinoma	0/171 (0%)		2/173 (1.2%)
Nervous system disorders
Apraxia	0/171 (0%)		1/173 (0.6%)
Carotid Artery Stenosis	1/171 (0.6%)		1/173 (0.6%)
Cerebrovascular Accident	1/171 (0.6%)		0/173 (0%)
Sciatica	0/171 (0%)		1/173 (0.6%)
Transient Ischaemic Attack	0/171 (0%)		1/173 (0.6%)
Psychiatric disorders
Mental Status Changes	0/171 (0%)		1/173 (0.6%)
Suicidal Ideation	1/171 (0.6%)		0/173 (0%)
Renal and urinary disorders
Bladder Neck Obstruction	1/171 (0.6%)		0/173 (0%)
Glomerulonephritis Rapidly Progressive	0/171 (0%)		1/173 (0.6%)
Mesangioproliferative Glomerulonephritis	0/171 (0%)		1/173 (0.6%)
Nephrolithiasis	2/171 (1.2%)		0/173 (0%)
Renal Failure Acute	2/171 (1.2%)		2/173 (1.2%)
Reproductive system and breast disorders
Benign Prostatic Hyperpasia	0/171 (0%)		1/173 (0.6%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	2/171 (1.2%)		3/173 (1.7%)
Chronic Obstructive Pulmonary Disease	0/171 (0%)		1/173 (0.6%)
Dyspnoea	1/171 (0.6%)		1/173 (0.6%)
Haemoptysis	0/171 (0%)		1/173 (0.6%)
Hypoxia	0/171 (0%)		2/173 (1.2%)
Idiopathic Pulmonary Fibrosis	13/171 (7.6%)		17/173 (9.8%)
Pleural Effusion	1/171 (0.6%)		0/173 (0%)
Pneumothorax	1/171 (0.6%)		1/173 (0.6%)
Productive Cough	1/171 (0.6%)		0/173 (0%)
Respiratory Arrest	0/171 (0%)		1/173 (0.6%)
Respiratory Distress	0/171 (0%)		1/173 (0.6%)
Respiratory Failure	4/171 (2.3%)		6/173 (3.5%)
Vascular disorders
Aortic Aneurysm	0/171 (0%)		1/173 (0.6%)
Hypertension	0/171 (0%)		2/173 (1.2%)
Hypotension	2/171 (1.2%)		1/173 (0.6%)
Malignant Hypertension	1/171 (0.6%)		0/173 (0%)
Thrombosis	1/171 (0.6%)		0/173 (0%)
Other (Not Including Serious) Adverse Events
	Pirfenidone (2403 mg/d)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	169/171 (98.8%)		170/173 (98.3%)
Metabolism and nutrition disorders
Anorexia	18/171 (10.5%)		6/173 (3.5%)
Decreased appetite	13/171 (7.6%)		9/173 (5.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	16/171 (9.4%)		11/173 (6.4%)
Back Pain	21/171 (12.3%)		15/173 (8.7%)
Musculoskeletal Pain	6/171 (3.5%)		9/173 (5.2%)
Pain in Extremity	11/171 (6.4%)		11/173 (6.4%)
Nervous system disorders
Dizziness	30/171 (17.5%)		18/173 (10.4%)
Headache	28/171 (16.4%)		25/173 (14.5%)
Psychiatric disorders
Anxiety	6/171 (3.5%)		10/173 (5.8%)
Depression	10/171 (5.8%)		7/173 (4%)
Insomnia	12/171 (7%)		11/173 (6.4%)
Respiratory, thoracic and mediastinal disorders
Cough	51/171 (29.8%)		54/173 (31.2%)
Dyspnoea	28/171 (16.4%)		34/173 (19.7%)
Idiopathic Pulmonary Fibrosis	31/171 (18.1%)		40/173 (23.1%)
Nasal Congestion	12/171 (7%)		14/173 (8.1%)
Pharyngolaryngeal pain	8/171 (4.7%)		11/173 (6.4%)
Postnasal Drip	7/171 (4.1%)		12/173 (6.9%)
Productive Cough	11/171 (6.4%)		3/173 (1.7%)
Respiratory Failure	5/171 (2.9%)		8/173 (4.6%)
Rhinitis Allergic	11/171 (6.4%)		4/173 (2.3%)
Skin and subcutaneous tissue disorders
Photosensitivity reaction	17/171 (9.9%)		4/173 (2.3%)
Pruritus	10/171 (5.8%)		8/173 (4.6%)
Rash	58/171 (33.9%)		22/173 (12.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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