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

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2012-000564-14-AT
• Date of registration: 11/06/2013
• Prospective Registration: Yes
• Primary sponsor: InterMune International AG.
• Public 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
• Scientific 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 - PANORAMA
• Date of first enrolment: 19/07/2013
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000564-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

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

Contacts

• Name: Project Management
• Affiliation: Theorem Clinical Research GmbH

• Name: Project Management
• Affiliation: Theorem Clinical Research GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Clinical symptoms consistent with IPF of =3 months duration (relative to Day 1)
2. Diagnosis of IPF =3 months before Day 1 (and no more than 4 years ago). Diagnosis date is defined as the first instance in which a patient was informed of having IPF or there is documented evidence of UIP diagnosed by HRCT
3. Age =40 and 80 years inclusive, on Day 1
4. Diagnosis of UIP or IPF by HRCT and surgical lung biopsy (SLB). 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.
5. Extent of fibrotic changes (honeycombing, reticular changes) greater than the extent of emphysema on the HRCT scan
6. No features supporting an alternative diagnosis on SLB, transbronchial biopsy (TBB), or bronchoalveolar lavage (BAL), if available. (SLB, TBB and BAL are not required for entry into the study.)
7. Percent predicted FVC =50% and =90% at Screening, confirmed by central review
8. Percent predicted DLCO =30% and =90% corrected by hemoglobin, at Screening, confirmed by central review.
9. Forced expiratory volume in 1 second (FEV1)/FVC ratio =0.75 confirmed by central review

Must be on a dose of pirfenidone not less than 1602 mg/day for at least 8 weeks prior to randomization at Day 1.

10. Able to understand and sign a written informed consent form
11. 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
12. Women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree 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. If abstinence is not practiced, one of the two methods of birth control should be an oral contraceptive (e.g., oral contraceptive and a spermicide).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
1. Significant clinical worsening of IPF between Screen. and Day 1, in the opinion of the Inv.
2. Unlikely to comply with the requirements of this study, in the opinion of the Inv.
3. Patient-reported cigarette smoking within 3 months of Screen. or unwilling to avoid use of tobacco products throughout the study
4. Hist. 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
5. Known cause of interstitial lung disease, including but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, cryptogenic organizing pneumonia
6. Human immunodeficiency virus (HIV), viral hepatitis B or C
7. Clinical diagnosis of any connective tissue disease, including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis
8. 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)
9. In list for lung transplantation: expected to receive a lung transplant within 6 months from Day 1
10. Any hist. 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)
11. Any condition other than IPF that, in the opinion of the Inv., is likely to result in the death of the patient within the next 12 months
12. Hist. of severe hepatic impairment or end-stage liver disease
13. Hist. of end-stage renal disease requiring dialysis
14. Hist. of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous 6 months (relative to Day 1), including but not limited to the following:
a. Unstable angina pectoris or myocardial infarction
b. Congestive heart failure requiring hospitalization
c. Uncontrolled clinically significant arrhythmias
15. Any condition that, in the opinion of the Inv., might be significantly exacerbated by the known side effects associated with the administration of NAC taken as a single medication
16. Known or suspected presence of a peptic ulcer
17. Pregnancy or lactation
18. Hist. of alcohol or substance abuse in the past 2 years
19. Family or personal hist. of long QT syndrome
20. Any contraindications according to the current NAC-product SPC
21. Any of the following liver chemistry criteria above specified limits:
a. Total bilirubin above the upper limit of normal (ULN)
b. Aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) >2 x ULN
c. Alkaline phosphatase >2.5 x ULN
22. Creatinine clearance (CrCl) <30 mL/min, calculated using the Cockcroft-Gault formula
23. ECG with a heart-rate–corrected QT interval using Bazett’s formula (QTcB) >500 ms at Screening
24. Suspected intolerance, allergy, or hypersensitivity to NAC or any of its components
25. Known intolerance, allergy, or hypersensitivity to NAC or any of its components
26. Use of any of the following therapies within 28 days before randomization:
a. Any investigational therapy, defined as any drug that has not MA for any indication in the country of the participating site
b. Corticosteroids when used for the treatment of IPF (except for

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with Idiopathic Pulmonary Fibrosis (IPF)
MedDRA version: 17.0 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: Fluimucil® 600 mg effervescent tablets
Pharmaceutical Form: Effervescent tablet
INN or Proposed INN: ACETYLCYSTEINE
Other descriptive name: N-Acetylcysteine, (NAC)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Effervescent tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To assess the safety and tolerability of treatment with NAC (1800 mg/d) in patients with mild to moderate IPF on the background of pirfenidone therapy.

Secondary Objective: None

Timepoint(s) of evaluation of this end point: • Telephone interviews: W2, W8, W16, W20
• Review of AEs/SAEs, concomitant meds, supplemental O2 use: Screening and washout, D1, W2, W4, W8, W12, W16, W20, W24, Follow-up
• Changes in clinical laboratory findings: Screening and washout, D1, W4, W12, W24, follow-up
• Spirometry and 6MWT procedure and Borg scale, UCSD SOBQ, DLCO: screening (DLCO only), D1, W12, W24

Primary end point(s): • Tolerability assessment and safety: Review of AEs/SAEs, dose reductions and discontinuations, changes in clinical laboratory findings, and deaths
• Worsening of the disease: Spirometry, 6MWT procedure and DLCO
• IPF exacerbations

Secondary Outcome(s)

Secondary end point(s): not applicable

Timepoint(s) of evaluation of this end point: not applicable

Secondary ID(s)

2012-000564-14-BE

PIPF-023

Source(s) of Monetary Support

InterMune International AG.