A Study to Assess the Safety and Tolerability of N-Acetylcysteine When Administered With Pirfenidone to Participants With Idiopathic Pulmonary Fibrosis (IPF)

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of the Safety and Tolerability of N-Acetylcysteine in Patients With Idiopathic Pulmonary Fibrosis With Background Treatment of Pirfenidone

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02707640

Enrollment

123

Registered

2016-03-14

Start date

2013-08-31

Completion date

2015-02-28

Last updated

2016-05-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Idiopathic Pulmonary Fibrosis

Brief summary

This is a Phase 2, randomized, double-blind, placebo-controlled safety and tolerability study of N-acetylcysteine or placebo in participants with mild to moderate idiopathic pulmonary fibrosis (IPF) receiving background pirfenidone therapy.

Interventions

DRUGMatching Placebo

Matching Placebo, oral administration, three times daily for 24 weeks.

DRUGN-acetylcysteine

N-acetylcysteine, 600 mg, oral administration, three times daily for 24 weeks.

DRUGPirfenidone

Pirfenidone, at least 1602 mg/day, oral administration, for 32 weeks, during the wash-out and screening period and for at least 8 weeks prior to randomization.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 80 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Dose Reductions	From baseline up to 24 weeks	Percentage of participants with dose reductions in N-Acetylcysteine and placebo cohorts during the 24-week treatment period.
Percentage of Participants With Early Treatment Discontinuations	From baseline up to 24 weeks	Percentage of participants with early treatment discontinuations in N-Acetylcysteine and placebo cohorts during the 24-week treatment period.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	Until 28 days from last dose of study treatment (Week 28)	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.
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)	Until 28 days from last dose of study treatment (Week 28)	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.
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	Until 28 days from last dose of study treatment (Week 28)	—
Percentage of Participants With Treatment-Emergent Adverse Events That Led to Dose Reduction or Temporary Discontinuation of Study Treatment	Until 28 days from last dose of study treatment (Week 28)	—

Countries

Austria, Belgium, Denmark, France, Germany, Italy, Sweden, United Kingdom

Participant flow

Participants by arm

Arm	Count
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.	60
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.	62
Total	122

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	4	2
Overall Study	Death	1	2
Overall Study	Participant's Personal Decision	1	2
Overall Study	Physician Decision	2	0
Overall Study	Sponsor Discretion	1	0
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	N-Acetylcysteine (NAC)	Placebo	Total
Age, Continuous	66.7 years STANDARD_DEVIATION 7.99	67.5 years STANDARD_DEVIATION 6.22	67.1 years STANDARD_DEVIATION 7.13
Sex: Female, Male Female	7 Participants	11 Participants	18 Participants
Sex: Female, Male Male	53 Participants	51 Participants	104 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	46 / 60	50 / 62
serious Total, serious adverse events	3 / 60	4 / 62

Outcome results

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.

Time frame: From baseline up to 24 weeks

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

Arm	Measure	Value (NUMBER)
N-Acetylcysteine (NAC)	Percentage of Participants With Dose Reductions	5 percentage of participants
Placebo	Percentage of Participants With Dose Reductions	4.8 percentage of participants

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.

Time frame: From baseline up to 24 weeks

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

Arm	Measure	Value (NUMBER)
N-Acetylcysteine (NAC)	Percentage of Participants With Early Treatment Discontinuations	14.8 percentage of participants
Placebo	Percentage of Participants With Early Treatment Discontinuations	11.3 percentage of participants

Primary