Trial Outcomes & Findings for Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome (NCT NCT00001596)

Last Updated: 2017-10-16

Results Overview

Change from baseline in the Forced Vital Capacity (FVC) measurement at 36 months. FVC is the volume of air that can be forcibly blown out from the lungs after full inspiration. FVC is recorded as the percentage of predicted volume (predicted FVC volume is calculated based on subject's height, age, sex, and weight).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Measured at baseline and 36 months

Results posted on

2017-10-16

Participant Flow

Patients were enrolled at the NIH Clinical Center between September 2005 to March 2009.

Participant milestones

Participant milestones
Measure	Pirfenidone Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo Subjects received placebo (3 pills), three times daily.
Overall Study STARTED	23	12
Overall Study COMPLETED	6	2
Overall Study NOT COMPLETED	17	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Pirfenidone Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo Subjects received placebo (3 pills), three times daily.
Overall Study Death	1	0
Overall Study Withdrawal by Subject	3	1
Overall Study Study Termination	12	9
Overall Study Adverse Event	1	0

Baseline Characteristics

Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pirfenidone n=23 Participants Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=12 Participants Subjects received placebo (3 pills), three times daily.	Total n=35 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	12 Participants n=7 Participants	34 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	39.53 years STANDARD_DEVIATION 11.00 • n=5 Participants	43.97 years STANDARD_DEVIATION 8.02 • n=7 Participants	41.05 years STANDARD_DEVIATION 10.18 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	6 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	12 participants n=7 Participants	35 participants n=5 Participants
Forced Vital Capacity	72.77 % of predicted STANDARD_DEVIATION 8.12 • n=5 Participants	73.53 % of predicted STANDARD_DEVIATION 10.09 • n=7 Participants	73.03 % of predicted STANDARD_DEVIATION 8.70 • n=5 Participants
Total Lung Capacity	73.84 % of predicted volume STANDARD_DEVIATION 12.07 • n=5 Participants	73.28 % of predicted volume STANDARD_DEVIATION 10.09 • n=7 Participants	73.65 % of predicted volume STANDARD_DEVIATION 11.28 • n=5 Participants
Adjusted Diffusing Capacity of the Lung for Carbon Monoxide	67.82 % of predicted volume STANDARD_DEVIATION 15.94 • n=5 Participants	66.83 % of predicted volume STANDARD_DEVIATION 16.60 • n=7 Participants	67.48 % of predicted volume STANDARD_DEVIATION 15.93 • n=5 Participants
6 Minute Walk Test	517.39 meters STANDARD_DEVIATION 112.79 • n=5 Participants	526.87 meters STANDARD_DEVIATION 103.00 • n=7 Participants	520.65 meters STANDARD_DEVIATION 107.94 • n=5 Participants

PRIMARY outcome

Timeframe: Measured at baseline and 36 months

Population: Participants from the Intent to Treat population for whom data was available at baseline and 36 months.

Outcome measures

Outcome measures
Measure	Pirfenidone n=11 Participants Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=3 Participants Subjects received placebo (3 pills), three times daily.
Change in Forced Vital Capacity (36 Months)	-23.52 % of predicted volume Standard Deviation 24.32	-20.93 % of predicted volume Standard Deviation 25.59

SECONDARY outcome

Timeframe: Measured at baseline and 12 months

Population: Participants from the Intent to Treat population for whom data was available at baseline and 12 months.

Change from baseline in the Forced Vital Capacity (FVC) measurement at 12 months. FVC is the volume of air that can be forcibly blown out from the lungs after full inspiration. FVC is recorded as the percentage of predicted volume (predicted FVC volume is calculated based on subject's height, age, sex, and weight).

Outcome measures

Outcome measures
Measure	Pirfenidone n=18 Participants Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=12 Participants Subjects received placebo (3 pills), three times daily.
Change in Forced Vital Capacity (12 Months)	-7.27 % of predicted volume Standard Deviation 20.48	-3.55 % of predicted volume Standard Deviation 21.33

SECONDARY outcome

Timeframe: Measured at baseline and 36 months

Population: Participants from the Intent to Treat population for whom data is available at baseline and 36 months.

Change from baseline in Total Lung Capacity (TLC) measured at 36 months. TLC is the volume in the lungs at maximal inflation. TLC is recorded as the percentage of predicted volume based on subject's height, age, sex, and weight.

Outcome measures

Outcome measures
Measure	Pirfenidone n=11 Participants Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=3 Participants Subjects received placebo (3 pills), three times daily.
Change in Total Lung Capacity (36 Months)	-25.26 % of predicted volume Standard Deviation 24.42	-22.9 % of predicted volume Standard Deviation 23.69

SECONDARY outcome

Timeframe: Measured at baseline and 12 months

Population: Participants from the Intent to Treat population for whom data was available at baseline and 12 months.

Change from baseline in Total Lung Capacity (TLC) measured at 12 months. TLC is the volume in the lungs at maximal inflation. TLC is recorded as the percentage of predicted volume based on subject's height, age, sex, and weight.

Outcome measures

Outcome measures
Measure	Pirfenidone n=18 Participants Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=12 Participants Subjects received placebo (3 pills), three times daily.
Change in Total Lung Capacity (12 Months)	-8.96 % of predicted volume Standard Deviation 21.03	0.53 % of predicted volume Standard Deviation 21.27

SECONDARY outcome

Timeframe: Measured at baseline and 36 months

Population: Participants from the Intent to Treat population for whom data was available at baseline and 36 months.

Change from baseline in adjusted Diffusing Capacity of the lung for carbon monoxide (DLCOa) measured at 36 months. DLCOa measures gas uptake during a single inspiration in a standard time, adjusted for subject's hemoglobin levels.

Outcome measures

Outcome measures
Measure	Pirfenidone n=11 Participants Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=3 Participants Subjects received placebo (3 pills), three times daily.
Change in Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (36 Months)	-15.25 % of predicted volume Standard Deviation 29.89	-14.93 % of predicted volume Standard Deviation 29.74

SECONDARY outcome

Timeframe: Measured at baseline and 12 months

Population: Participants from the Intent to Treat population for whom data is available at baseline and 12 months.

Change from baseline in adjusted Diffusing Capacity of the lung for carbon monoxide (DLCOa) measured at 12 months. DLCOa measures gas uptake during a single inspiration in a standard time, adjusted for subject's hemoglobin levels.

Outcome measures

Outcome measures
Measure	Pirfenidone n=18 Participants Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=12 Participants Subjects received placebo (3 pills), three times daily.
Change in Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (12 Months)	-3.11 % of predicted volume Standard Deviation 26.47	-4.74 % of predicted volume Standard Deviation 25.97

SECONDARY outcome

Timeframe: Measured at baseline and 36 months

Population: Participants from the Intent to Treat population for whom data is available at baseline and 36 months.

Change from baseline of the 6 minute walk test (6MWT) at 36 months. The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.

Outcome measures

Outcome measures
Measure	Pirfenidone n=10 Participants Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=2 Participants Subjects received placebo (3 pills), three times daily.
Change in 6 Minute Walk Test (36 Months)	-232.86 meters Standard Deviation 284.26	-306.75 meters Standard Deviation 314.69

SECONDARY outcome

Timeframe: Measured at baseline and 12 months

Population: Participants from the Intent to Treat population for whom data is available at baseline and 12 months.

Change from baseline of the 6 minute walk test (6MWT) at 12 months. The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.

Outcome measures

Outcome measures
Measure	Pirfenidone n=16 Participants Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=12 Participants Subjects received placebo (3 pills), three times daily.
Change in 6 Minute Walk Test (12 Months)	-40.56 meters Standard Deviation 192.66	-17.21 meters Standard Deviation 201.21

Adverse Events

Pirfenidone

Serious events: 6 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pirfenidone n=23 participants at risk Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=12 participants at risk Subjects received placebo (3 pills), three times daily.
Investigations Blood creatinine phosphokinase increased	4.3% 1/23 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	8.3% 1/12 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Cardiac disorders Chest pain	8.7% 2/23 • Number of events 2 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Vascular disorders Deep vein thrombosis	4.3% 1/23 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Gastrointestinal disorders Haematochezia	4.3% 1/23 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Respiratory, thoracic and mediastinal disorders Respiratory failure	8.7% 2/23 • Number of events 2 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	8.3% 1/12 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.

Other adverse events

Additional Information

Dr. William A. Gahl

National Human Genome Research Institute

Phone: 301-402-2739

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Pirfenidone n=23 participants at risk Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.	Placebo n=12 participants at risk Subjects received placebo (3 pills), three times daily.
Gastrointestinal disorders Abdominal pain	0.00% 0/23 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	16.7% 2/12 • Number of events 2 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Musculoskeletal and connective tissue disorders Arthalgia	4.3% 1/23 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Cardiac disorders Chest pain	13.0% 3/23 • Number of events 3 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	8.3% 1/12 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Nervous system disorders Dizziness	17.4% 4/23 • Number of events 4 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Immune system disorders Drug eruption	8.7% 2/23 • Number of events 2 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Gastrointestinal disorders Dyspepsia	52.2% 12/23 • Number of events 12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	50.0% 6/12 • Number of events 6 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
General disorders Fatigue	8.7% 2/23 • Number of events 2 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/23 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	8.3% 1/12 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Gastrointestinal disorders Nausea	17.4% 4/23 • Number of events 4 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	8.3% 1/12 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Cardiac disorders Palpitations	13.0% 3/23 • Number of events 3 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Skin and subcutaneous tissue disorders Photosensitivity reaction	8.7% 2/23 • Number of events 2 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Skin and subcutaneous tissue disorders Rash	8.7% 2/23 • Number of events 2 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	16.7% 2/12 • Number of events 2 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Nervous system disorders Somnolence	4.3% 1/23 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Investigations Transaminases increased	4.3% 1/23 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Immune system disorders Urticaria	0.00% 0/23 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	8.3% 1/12 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Ear and labyrinth disorders Vertigo	4.3% 1/23 • Number of events 1 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	0.00% 0/12 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.
Gastrointestinal disorders Vomiting	0.00% 0/23 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.	16.7% 2/12 • Number of events 2 • Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.