Clinical trial NCT02707640: A Study to Assess the Safety and Tolerability of N-Acetylcysteine When Administered With Pirfenidone to Participants With Idiopathic Pulmonary Fibrosis (IPF)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-03-14
Enrollment: 123
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants With Dose Reductions
timeFrame: From baseline up to 24 weeks
measure: Percentage of Participants With Early Treatment Discontinuations
timeFrame: From baseline up to 24 weeks
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Until 28 days from last dose of study treatment (Week 28)
measure: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: Until 28 days from last dose of study treatment (Week 28)
measure: Percentage of Participants With Treatment-Emergent Adverse Events Resulting in Permanent Discontinuation of Study Treatment
timeFrame: Until 28 days from last dose of study treatment (Week 28)
measure: Percentage of Participants With Treatment-Emergent Deaths of All Causes
timeFrame: Until 28 days from last dose of study treatment (Week 28)
measure: Percentage of Participants With Treatment-Emergent Adverse Events That Led to Dose Reduction or Temporary Discontinuation of Study Treatment
timeFrame: Until 28 days from last dose of study treatment (Week 28)
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Salzburg
country: Austria
city: Bruxelles
country: Belgium
city: Leuven
country: Belgium
city: Mont-godinne
country: Belgium
city: Aarhus
country: Denmark
city: Hellerup
country: Denmark
city: Odense C
country: Denmark
city: Bobigny
country: France
city: Brest
country: France
city: Bron
country: France
city: Dijon
country: France
city: Lille
country: France
city: Marseille cedex 20
country: France
city: Montpellier
country: France
city: Paris
country: France
city: Reims
country: France
city: Rennes
country: France
city: Toulouse
country: France
city: Tours
country: France
city: Bad Berka
country: Germany
city: Bamberg
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Bonn
country: Germany
city: Coswig
country: Germany
city: Donaustauf
country: Germany
city: Essen
country: Germany
city: Freiburg
country: Germany
city: Gießen
country: Germany
city: Greifswald
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: Immenhausen
country: Germany
city: Magdeburg
country: Germany
city: Marburg
country: Germany
city: Muenchen
country: Germany
city: Münnerstadt
country: Germany
city: Solingen
country: Germany
city: Würzburg
country: Germany
city: Napoli
country: Italy
state: Campania
city: Cattinara Trieste
country: Italy
state: Friuli-Venezia Giulia
city: Trieste
country: Italy
state: Friuli-Venezia Giulia
city: Roma
country: Italy
state: Lazio
city: Catania
country: Italy
state: Liguria
city: Milano
country: Italy
state: Lombardia
city: Monza
country: Italy
state: Lombardia
city: Orbassano
country: Italy
state: Piemonte
city: Pisa
country: Italy
state: Toscana
city: Siena
country: Italy
state: Toscana
city: Padova
country: Italy
state: Veneto
city: Falun
country: Sweden
city: Lund
country: Sweden
city: Stokholm, Solna
country: Sweden
city: Uppsala
country: Sweden
city: Bristol
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Exeter
country: United Kingdom
city: Leeds
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Oxford
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: