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

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Matching Placebo; Drug: Pirfenidone; Drug: N-acetylcysteine

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
  • Innsbruck, Austria, 6020
  • Salzburg, Austria, 5020
• Belgium
  • Bruxelles, Belgium, 1070
  • Leuven, Belgium, 3000
  • Mont-godinne, Belgium, 5530
• Denmark
  • Aarhus, Denmark, 8000
  • Hellerup, Denmark, 2900
  • Odense C, Denmark, 5000
• France
  • Bobigny, France, 93000
  • Brest, France, 29609
  • Bron, France, 69677
  • Dijon, France
  • Lille, France, 59037
  • Marseille cedex 20, France, 13915
  • Montpellier, France, 34295
  • Paris, France, 75877
  • Reims, France, 51092
  • Rennes, France, 35033
  • Toulouse, France, 31059
  • Tours, France, 37044
• Germany
  • Bad Berka, Germany, 99437
  • Bamberg, Germany
  • Berlin, Germany, 10117
  • Berlin, Germany, 13125
  • Berlin, Germany, 14165
  • Bochum, Germany, 44789
  • Bonn, Germany, 53127
  • Coswig, Germany, 01640
  • Donaustauf, Germany, 93093
  • Essen, Germany, 45239
  • Freiburg, Germany
  • Gießen, Germany, 35392
  • Greifswald, Germany, 17475
  • Hamburg, Germany
  • Heidelberg, Germany, 69126
  • Immenhausen, Germany, 34376
  • Magdeburg, Germany, 39120
  • Marburg, Germany, 35037
  • Muenchen, Germany, 81377
  • Münnerstadt, Germany
  • Solingen, Germany, 42699
  • Würzburg, Germany
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
  • Friuli-Venezia Giulia
    • Cattinara Trieste, Friuli-Venezia Giulia, Italy, 34149
    • Trieste, Friuli-Venezia Giulia, Italy, 34129
  • Lazio
    • Roma, Lazio, Italy, 00133
  • Liguria
    • Catania, Liguria, Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20142
    • Monza, Lombardia, Italy, 20900
  • Piemonte
    • Orbassano, Piemonte, Italy, 10043
  • Toscana
    • Pisa, Toscana, Italy, 56124
    • Siena, Toscana, Italy, 53100
  • Veneto
    • Padova, Veneto, Italy
• Sweden
  • Falun, Sweden, 79182
  • Lund, Sweden, 221 85
  • Stokholm, Solna, Sweden, 17176
  • Uppsala, Sweden, 751 85
• United Kingdom
  • Bristol, United Kingdom, BS10-5NB
  • Cambridge, United Kingdom, CB23 3RE
  • Exeter, United Kingdom, EX2 5DW
  • Leeds, United Kingdom, LS9 7TF
  • Liverpool, United Kingdom, L9 7AL
  • London, United Kingdom
  • London, United Kingdom, NW1 2BU
  • London, United Kingdom, SW3 6NP
  • Oxford, United Kingdom
  • Sheffield, United Kingdom
  • Southampton, United Kingdom, SO16 6YD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Matching Placebo	Drug: Matching Placebo; Matching Placebo, oral administration, three times daily for 24 weeks.; Drug: Pirfenidone; 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.
EXPERIMENTAL: N-Acetylcysteine	Drug: Pirfenidone; 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.; Drug: N-acetylcysteine; N-acetylcysteine, 600 mg, oral administration, three times daily for 24 weeks.
OTHER: Pirfenidone; Background therapy	Drug: Pirfenidone; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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		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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: March 9, 2016
• First Submitted That Met QC Criteria: March 9, 2016
• First Posted (ESTIMATE): March 14, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): May 20, 2016
• Last Update Submitted That Met QC Criteria: April 14, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Pirfenidone; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: WA29976; 2012-000564-14 (EUDRACT_NUMBER)