Non-cystic fibrosis bronchiectasis chronically infected with Pseudomonas aeruginosa MedDRA version: 21.0 Level: PT Classification code 10006445 Term: Bronchiectasis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Zambon S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects can be included in the trial if they meet all the inclusion criteria listed below: 1) are able and willing to give informed consent, following a detailed explanation of participation in the protocol and signed consent obtained; 2) are aged 18 years or older of either gender; 3) are diagnosed with NCFB by computerised tomography (CT) or high resolution CT (HRCT) as recorded in the subject's notes and this is their predominant condition being treated; 4) had at least 2 NCFB pulmonary exacerbations requiring oral or inhaled antibiotics or 1 NCFB pulmonary exacerbation requiring intravenous antibiotics in the 12 months preceding the Screening Visit (Visit 1) and had no NCFB pulmonary exacerbation with or without treatment during the period between Visit 1 and Visit 2; 5) have a documented history of P. aeruginosa infection; 6) had 1 positive sputum culture for P. aeruginosa in the 12 months preceding the Screening Visit (but performed at least 30 days before the Screening Visit); 7) are clinically stable and have not required a change in pulmonary treatment for at least 30 days before the Screening Visit (Visit 1); 8) have pre-bronchodilator FEV1 =30% of predicted; 9) had a positive sputum culture for P. aeruginosa from an adequate sample taken at the Screening Visit (Visit 1) or during the screening period. 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 210 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 210
Exclusion criteria
Exclusion criteria: Subjects are not eligible for the trial if they meet one or more of the exclusion criteria listed below: 1) known bronchiectasis as a consequence of cystic fibrosis (CF); 2) known history of hypogammaglobulinaemia requiring treatment with immunoglobulin, unless fully replaced and considered immuno-competent by the Investigator; 3) myasthenia gravis or porphyria ; 4) severe cardiovascular disease such as severe uncontrolled hypertension, ischaemic heart disease or cardiac arrhythmia and any other conditions that would confound the evaluation of safety, in the opinion of the Investigator; 5) had major surgery in the 3 months prior to the Screening Visit (Visit 1) or planned inpatient major surgery during the study period; 6) receiving treatment for allergic bronchopulmonary aspergillosis (ABPA); 7) had massive haemoptysis (greater than or equal to 300 mL or requiring blood transfusion) in the preceding 4 weeks before the Screening Visit (Visit 1) or between Visit 1 and Visit 2; 8) predominant lung condition being chronic obstructive pulmonary disease (COPD), asthma or interstitial lung disease in the opinion of the Investigator; 9) respiratory failure that would compromise patient safety or confound the evaluation of safety or efficacy of the study in the opinion of the Investigator; 10) receiving long term oxygen therapy or non-invasive ventilation for the management of respiratory failure; 11) current active malignancy, except for basal cell carcinoma of the skin without metastases; 12) taking immunosuppressive medications (such as azathioprine, methotrexate, ciclosporine, tacrolimus, sirolimus, mycophenolate, rituximab), and/or anti-cytokine medications (such as anti IL-6 and antitumour alpha necrosis factor products) in the preceding year before the Screening Visit (Visit 1); 13) known history of human immunodeficiency virus (HIV); 14) current diagnosis or current treatment for non-tuberculous mycobacterium (NTM) lung disease or tuberculosis. 16) known or suspected to be allergic or unable to tolerate colistimethate sodium (intravenous or inhaled) or other polymixins, including previous evidence of bronchial hyperreactivity following inhaled colistimethate sodium; 17) treatment with long term (= 30 days) prednisone at a dose greater than 15 mg a day (or equivalent dose of any other corticosteroid) within six months of the Screening Visit (Visit 1) 18) new maintenance treatment with oral macrolides (e.g. azithromycin/erythromycin/clarithromycin) started within 30 days of the Screening Visit (Visit 1) and between Visit 1 and Visit 2; 19) use of any intravenous or intramuscular or oral or inhaled antipseudomonal antibiotic (except chronic oral macrolide treatment with a stable dose) within 30 days prior to the Screening Visit (Visit 1); 20) pregnant or breast feeding or plan to become pregnant over the next year or of child bearing potential and unwilling to use a reliable method of contraception for at least one month before randomisation and throughout their involvement in the trial; 21) significant abnormality in clinical evaluations and/or laboratory tests (physical examination, vital signs, haematology, clinical chemistry, clinically relevant impaired renal function, defined as serum creatinine levels =2.0x upper limit of normal, ECG) endangering the safe participation of the patient in the study at the Screening Visit (Visit 1) and during the study; 22) participated in another investigational, interventional trial within 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to investigate the effect of the use of inhaled colistimethate sodium, administered twice daily via the I-neb for 12 months, compared to placebo in subjects with NCFB chronically infected with P. aeruginosa on the frequency of pulmonary exacerbations.;Secondary Objective: The secondary objectives of the trial are to investigate the effect of the use of inhaled colistimethate sodium, administered twice daily via the Ineb for 12 months, compared to placebo in subjects with NCFB chronically infected with P. aeruginosa on: • the time to the first NCFB pulmonary exacerbation; •to investigate the effect of the use of inhaled colistimethate sodium, administered twice daily via the I-neb for 12 months, on the number of exacerbation-free days; • number of severe NCFB pulmonary exacerbations, defined as those requiring intravenous antibiotics and/or hospitalisation; • the time to the first NFCB severe pulmonary exacerbation; • Quality of Life; • pharmaco-economic evaluation; • P. aeruginosa density and susceptibility and the emergence of other bacterial colonies and any developing resistance to colistin; • Overall safety and tolerability.;Primary end point(s): Primary Efficacy Variable: Mean annual pulmonary exacerbation rate.;Timepoint(s) of evaluation of this end point: At 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Variables: • the time (in days) from the first dose of IMP until the first pulmonary exacerbation; • annualised number of pulmonary exacerbation-free days; • number of severe pulmonary exacerbations, defined as those requiring intravenous antibiotics and/or hospitalisation; • the time (in days) from the first dose of IMP until the first severe pulmonary exacerbation; • quality of life (QoL) as measured by the total score of the Saint George's Respiratory Questionnaire (SGRQ) and Quality of Life – Bronchiectasis (QOL B) questionnaire as well as changes in SGRQ and QOL-B from baseline to each post-baseline visit; • number of days of work absence due to pulmonary exacerbations; • P. aeruginosa density as determined by the mean change in log10 colony forming units (CFU)/g sputum from baseline (Visit 2) to Day 28 of treatment (Visit 3) as well as to Visits 5 and 7, inclusive. Safety Variables: • incidence of treatment emergent adverse events (TEAEs); • absolute changes in percent-predicted FEV1 from baseline (Visit 2) to end of treatment (Visit 7); • number of subjects experiencing bronchospasm clinically or spirometrically determined following IMP administration at the end of treatment; • P. aeruginosa resistance to colistin sulphate as determined by in-vitro susceptibility testing on sputum from Screening (Visit 1) to end of treatment (Visit 7) as well as on sputum from Exacerbation Visits and clinic visits due to pneumonia; • emergence of other bacterial colonies and any developing resistance in sputum from Screening (Visit 1) to End of Treatment (Visit 7); • haematology, clinical chemistry and renal function tests; • physical examination and vital signs data; • 12-lead electrocardiogram.;Timepoint(s) of evaluation of this end point: For timepoints, please refer protocol Section 18.2 Study Variables and Protocol Appendix 1 | — |
Countries
Australia, Belgium, France, Germany, Greece, Israel, Italy, Netherlands, New Zealand, Portugal, Spain, Switzerland, United Kingdom
Contacts
Public ContactDearbhla Hull
Zambon S.p.A.
Outcome results
None listed