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

NCT02707640 | Completed Phase 2 Results

• 2 other identifiers: WA299762012-000564-14
• Study Type: interventional
• Target: 123
• Locations: 8 countries
• Sites: 69

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.

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (7)

• 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)

Study Arms (3)

Matching Placebo

PLACEBO COMPARATOR

Drug: Matching Placebo; Drug: Pirfenidone

N-Acetylcysteine

EXPERIMENTAL

Drug: N-acetylcysteine; Drug: Pirfenidone

Pirfenidone

OTHER

Background therapy

Drug: Pirfenidone

Interventions

Matching Placebo DRUG

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

Matching Placebo

N-acetylcysteine DRUG

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

N-Acetylcysteine

Pirfenidone DRUG

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.

Matching Placebo; N-Acetylcysteine; Pirfenidone

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (69)

Unknown Facility

Graz, 8036, Austria

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Innsbruck, 6020, Austria

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Salzburg, 5020, Austria

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Brussels, 1070, Belgium

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Leuven, 3000, Belgium

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Mont-godinne, 5530, Belgium

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Aarhus, 8000, Denmark

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Hellerup, 2900, Denmark

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Odense C, 5000, Denmark

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Bobigny, 93000, France

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Brest, 29609, France

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Bron, 69677, France

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Dijon, France

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Lille, 59037, France

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Marseille, 13915, France

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Montpellier, 34295, France

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Paris, 75877, France

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Reims, 51092, France

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Rennes, 35033, France

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Toulouse, 31059, France

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Tours, 37044, France

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Bad Berka, 99437, Germany

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Bamberg, Germany

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Berlin, 10117, Germany

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Berlin, 13125, Germany

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Berlin, 14165, Germany

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Bochum, 44789, Germany

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Bonn, 53127, Germany

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Coswig, 01640, Germany

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Donaustauf, 93093, Germany

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Essen, 45239, Germany

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Freiburg im Breisgau, Germany

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Giessen, 35392, Germany

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Greifswald, 17475, Germany

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Hamburg, Germany

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Heidelberg, 69126, Germany

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Immenhausen, 34376, Germany

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Magdeburg, 39120, Germany

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Marburg, 35037, Germany

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München, 81377, Germany

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Münnerstadt, Germany

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Solingen, 42699, Germany

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Würzburg, Germany

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Napoli, Campania, 80131, Italy

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Cattinara Trieste, Friuli Venezia Giulia, 34149, Italy

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Trieste, Friuli Venezia Giulia, 34129, Italy

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Rome, Lazio, 00133, Italy

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Catania, Liguria, Italy

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Milan, Lombardy, 20142, Italy

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Monza, Lombardy, 20900, Italy

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Orbassano, Piedmont, 10043, Italy

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Pisa, Tuscany, 56124, Italy

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Siena, Tuscany, 53100, Italy

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Padua, Veneto, Italy

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Falun, 79182, Sweden

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Lund, 221 85, Sweden

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Stokholm, Solna, 17176, Sweden

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Uppsala, 751 85, Sweden

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Bristol, BS10-5NB, United Kingdom

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Cambridge, CB23 3RE, United Kingdom

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Exeter, EX2 5DW, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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Liverpool, L9 7AL, United Kingdom

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London, NW1 2BU, United Kingdom

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London, SW3 6NP, United Kingdom

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London, United Kingdom

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Oxford, United Kingdom

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Sheffield, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

Acetylcysteine; pirfenidone

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: March 14, 2016
• Study Start: August 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: May 20, 2016
• Results First Posted: May 20, 2016

Record last verified: 2016-04

Locations

BE (3); AU (3); FR (12); SE (4); IT (11); DE (22); GB (11); DK (3)