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

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02707640
• Other study ID #: WA29976
• Secondary ID: 2012-000564-14
• Status: Completed
• Phase: Phase 2
• First received: March 9, 2016
• Last updated: March 9, 2016
• Start date: August 2013
• Est. completion date: February 2015

Study information

• Verified date: March 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• Matching Placebo
Matching Placebo, oral administration, three times daily for 24 weeks.
• N-acetylcysteine
N-acetylcysteine, 600 mg, oral administration, three times daily for 24 weeks.
• Pirfenidone
Pirfenidone, at least 1602 mg/day, oral administration, for 32 weeks, beginning 8 weeks prior to administration of study medication.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of N-Acetylcysteine Treatment Discontinuations		From baseline up to 24 weeks	No
Primary	Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs)		Up to 34 weeks	No
Primary	Percentage of Participants with Treatment-Emergent Serious Adverse Events (SAEs)		Up to 34 weeks	No
Primary	Percentage of Treatment-Emergent Deaths for all Causes		Up to 34 weeks	No
Primary	Percentage of Treatment-Emergent Adverse Events Resulting in Permanent Discontinuation of Study Treatment		Up to 34 weeks	No
Primary	Percentage of Treatment-Emergent Adverse Events that Led to Dose Reduction or Temporary Discontinuation of Study Treatment		Up to 34 weeks	No
Primary	Percentage of Participants with N-Acetylcysteine Dose Reductions		From baseline up to 24 weeks	No