A Study to Assess the Safety and Tolerability of N-Acetyl... | NCT02707640

ID	Type	Description	Link
2012-000564-14	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Matching Placebo	Placebo Comparator		Drug: Matching Placebo Drug: Pirfenidone
N-Acetylcysteine	Experimental		Drug: N-acetylcysteine Drug: Pirfenidone
Pirfenidone	Other	Background therapy	Drug: Pirfenidone

Name	Type	Description	Arm Group Labels	Other Names
Matching Placebo	Drug	Matching Placebo, oral administration, three times daily for 24 weeks.	Matching Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Dose Reductions	Percentage of participants with dose reductions in N-Acetylcysteine and placebo cohorts during the 24-week treatment period.	From baseline up to 24 weeks
Percentage of Participants With Early Treatment Discontinuations	Percentage of participants with early treatment discontinuations in N-Acetylcysteine and placebo cohorts during the 24-week treatment period.	From baseline up to 24 weeks
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) is defined as any untoward medical occurrence in a participant who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment.	Until 28 days from last dose of study treatment (Week 28)
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)	A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of hospitalization, or results in disability/incapacity, or congenital anomaly/birth defect.	Until 28 days from last dose of study treatment (Week 28)
Percentage of Participants With Treatment-Emergent Adverse Events Resulting in Permanent Discontinuation of Study Treatment		Until 28 days from last dose of study treatment (Week 28)
Percentage of Participants With Treatment-Emergent Deaths of All Causes

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Clinical symptoms consistent with IPF of >=3 months' duration (relative to Day 1)
Must have been on a dose of pirfenidone not less than 1602 mg/day for at least 8 weeks prior to randomization at Day 1
Able to understand the importance of adherence to study treatment and the study protocol and willing to follow all study requirements, including the concomitant medication restrictions, throughout the study
Women of childbearing capacity were required to have a negative serum pregnancy test before treatment and must have agreed to maintain highly effective contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study
Diagnosis of usual interstitial pneumonia (UIP) or IPF by high-resolution computed tomography (HRCT) and surgical lung biopsy. Previous HRCT scans, typically and if available, one at the point of time of diagnosis and one more recent, made during the last year before study inclusion, will be used and assessed by a central Reading Committee

Exclusion Criteria:

Significant clinical worsening of IPF between screening and Day 1 of study, in the opinion of the investigator
Unlikely to comply with the requirements of this study, in the opinion of the investigator
Patient-reported cigarette smoking within 3 months of screening or unwilling to avoid use of tobacco products throughout the study
History of clinically significant environmental exposure known to cause pulmonary fibrosis (PF), including but not limited to drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds
Known cause of interstitial lung disease, including but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, and cryptogenic organizing pneumonia
Clinical diagnosis of any connective tissue disease, including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis
Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis (as a diffuse inflammation of connective tissue and or skin)
Any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 6 months (relative to Day 1). This does not include minor surgical procedures for localized cancer (e.g., basal cell carcinoma, squamous skin carcinoma)
History of severe hepatic impairment or end-stage liver disease
History of end-stage renal disease requiring dialysis
History of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous 6 months (relative to Day 1)
Any condition that, in the opinion of the investigator, may have been significantly exacerbated by the known side effects associated with the administration of N-acetylcysteine taken as a single medication
Suspected intolerance, allergy, or hypersensitivity to pirfenidone or any of its components
Known intolerance, allergy, or hypersensitivity to N-acetylcysteine or any of its components

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	N-Acetylcysteine (NAC)	Participants randomized to this arm were administered 600 milligram (mg) NAC orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	N-Acetylcysteine (NAC)	Participants randomized to this arm were administered 600 milligram (mg) NAC orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.
BG001	Placebo	Participants randomized to this arm were administered matching placebo orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Dose Reductions

Percentage of participants with dose reductions in N-Acetylcysteine and placebo cohorts during the 24-week treatment period.

mITT population included participants who received at least 1 dose of double-blind study medication (NAC or placebo).

Posted

Number

percentage of participants

From baseline up to 24 weeks

ID	Title	Description
OG000	N-Acetylcysteine (NAC)	Participants randomized to this arm were administered 600 milligram (mg) NAC orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.
OG001	Placebo	Participants randomized to this arm were administered matching placebo orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.

Units	Counts
Participants	OG00060 OG00162

Title

Denominators

Categories

Title	Measurements
	OG0005 OG0014.8

Primary

Percentage of Participants With Early Treatment Discontinuations

Percentage of participants with early treatment discontinuations in N-Acetylcysteine and placebo cohorts during the 24-week treatment period.

mITT population included participants who received at least 1 dose of double-blind study medication (NAC or placebo).

Posted

Number

percentage of participants

From baseline up to 24 weeks

ID	Title	Description
OG000	N-Acetylcysteine (NAC)	Participants randomized to this arm were administered 600 milligram (mg) NAC orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.
OG001	Placebo	Participants randomized to this arm were administered matching placebo orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.

Units	Counts

Primary

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) is defined as any untoward medical occurrence in a participant who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment.

mITT Population included participants who received at least 1 dose of double-blind study medication (NAC or placebo).

Posted

Number

percentage of participants

Until 28 days from last dose of study treatment (Week 28)

ID	Title	Description
OG000	N-Acetylcysteine (NAC)	Participants randomized to this arm were administered 600 milligram (mg) NAC orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.
OG001	Placebo	Participants randomized to this arm were administered matching placebo orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.

Primary

Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of hospitalization, or results in disability/incapacity, or congenital anomaly/birth defect.

mITT population included who received at least 1 dose of double-blind study medication (NAC or placebo).

Posted

Number

percentage of participants

Until 28 days from last dose of study treatment (Week 28)

ID	Title	Description
OG000	N-Acetylcysteine (NAC)	Participants randomized to this arm were administered 600 milligram (mg) NAC orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.
OG001	Placebo	Participants randomized to this arm were administered matching placebo orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.

Primary

Percentage of Participants With Treatment-Emergent Adverse Events Resulting in Permanent Discontinuation of Study Treatment

mITT population included who received at least 1 dose of double-blind study medication (NAC or placebo).

Posted

Number

percentage of participants

Until 28 days from last dose of study treatment (Week 28)

ID	Title	Description
OG000	N-Acetylcysteine (NAC)	Participants randomized to this arm were administered 600 milligram (mg) NAC orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.
OG001	Placebo	Participants randomized to this arm were administered matching placebo orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.

Units	Counts
Participants

Primary

Percentage of Participants With Treatment-Emergent Deaths of All Causes

mITT population included who received at least 1 dose of double-blind study medication (NAC or placebo).

Posted

Number

percentage of participants

Until 28 days from last dose of study treatment (Week 28)

ID	Title	Description
OG000	N-Acetylcysteine (NAC)	Participants randomized to this arm were administered 600 milligram (mg) NAC orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.
OG001	Placebo	Participants randomized to this arm were administered matching placebo orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.

Units	Counts
Participants

Primary

Percentage of Participants With Treatment-Emergent Adverse Events That Led to Dose Reduction or Temporary Discontinuation of Study Treatment

mITT population included who received at least 1 dose of double-blind study medication (NAC or placebo).

Posted

Number

percentage of participants

Until 28 days from last dose of study treatment (Week 28)

ID	Title	Description
OG000	N-Acetylcysteine (NAC)	Participants randomized to this arm were administered 600 milligram (mg) NAC orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.
OG001	Placebo	Participants randomized to this arm were administered matching placebo orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	N-Acetylcysteine (NAC)	Participants randomized to this arm were administered 600 milligram (mg) NAC orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.			3	60	46	60
EG001	Placebo	Participants randomized to this arm were administered matching placebo orally three times daily and a dose of pirfenidone of at least 1602 mg/day for 24 weeks. Participants were to be on a dose of pirfenidone of at least 1602 mg/day for a minimum of 8 weeks prior to randomization and were followed until 4 weeks after last study treatment dose.			4	62	50	62

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
CONTUSION	Injury, poisoning and procedural complications	MedDRA 11.0	Systematic Assessment	EG0000 affected60 at risk EG0011 affected62 at risk
FOREARM FRACTURE	Injury, poisoning and procedural complications	MedDRA 11.0	Systematic Assessment	EG0000 affected60 at risk EG0011 affected62 at risk
INTERVERTEBRAL DISC PROTRUSION	Musculoskeletal and connective tissue disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected60 at risk EG0010 affected62 at risk
LUNG NEOPLASM MALIGNANT	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.0	Systematic Assessment	EG0001 affected60 at risk EG0010 affected62 at risk
HEADACHE	Nervous system disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected60 at risk EG0010 affected62 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected60 at risk EG0010 affected62 at risk
IDIOPATHIC PULMONARY FIBROSIS	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected60 at risk EG0012 affected62 at risk
AORTIC ANEURYSM	Vascular disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected60 at risk EG0011 affected62 at risk
HYPERTENSION	Vascular disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected60 at risk EG0010 affected62 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0004 affected60 at risk EG0010 affected62 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0006 affected60 at risk EG0019 affected62 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0004 affected60 at risk EG0015 affected62 at risk
BRONCHITIS	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0004 affected60 at risk EG0013 affected62 at risk
INFLUENZA	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0003 affected60 at risk EG0011 affected62 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0007 affected60 at risk EG0017 affected62 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0003 affected60 at risk EG0015 affected62 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA 11.0	Systematic Assessment	EG0003 affected60 at risk EG0011 affected62 at risk
HEADACHE	Nervous system disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected60 at risk EG0015 affected62 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Systematic Assessment	EG0008 affected60 at risk EG0017 affected62 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Systematic Assessment	EG0003 affected60 at risk EG0014 affected62 at risk
PRODUCTIVE COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Systematic Assessment	EG0003 affected60 at risk EG0012 affected62 at risk
DRY SKIN	Skin and subcutaneous tissue disorders	MedDRA 11.0	Systematic Assessment	EG0003 affected60 at risk EG0010 affected62 at risk
PHOTOSENSITIVITY REACTION	Skin and subcutaneous tissue disorders	MedDRA 11.0	Systematic Assessment	EG0008 affected60 at risk EG0011 affected62 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA 11.0	Systematic Assessment	EG0002 affected60 at risk EG0016 affected62 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Graz		8036	Austria

ID	Term
D011658	Pulmonary Fibrosis
D017563	Lung Diseases, Interstitial
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D003545	Cysteine
D000603	Amino Acids, Sulfur
D013457	Sulfur Compounds
D009930	Organic Chemicals
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins