A double-blind, placebo controlled, multicentre, clinical trial to investigate the efficacy and safety of 12 months of therapy with inhaled Promixin® (colistimethate sodium) in the treatment of subjects with non-cystic fibrosis bronchiectasis chronically infected with Pseudomonas aeruginosa (P. aeruginosa)

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2016-004558-13-FR
• Date of registration: 20/03/2017
• Prospective Registration: Yes
• Primary sponsor: Zambon S.p.A.
• Public title: A double-blind, placebo controlled, multicentre, clinical trial to investigate the efficacy and safety of 12 months of therapy with inhaled Promixin® (colistimethate sodium) in the treatment of subjects with non-cystic fibrosis bronchiectasis chronically infected with Pseudomonas aeruginosa (P. aeruginosa)
• Scientific title: A double-blind, placebo controlled, multicentre, clinical trial to investigate the efficacy and safety of 12 months of therapy with inhaled Promixin® (colistimethate sodium) in the treatment of subjects with non-cystic fibrosis bronchiectasis chronically infected with Pseudomonas aeruginosa (P. aeruginosa) - PROMIS II
• Date of first enrolment: 30/05/2017
• Target sample size: 264
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004558-13
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, France, Germany, Greece, Italy, Poland, Portugal, United States

Contacts

• Name: Regulatory Service
• Affiliation: Chiltern International Ltd

• Name: Regulatory Service
• Affiliation: Chiltern International Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects can be included in the trial if they meet all 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. Aged 18 years or older of either genders;
3. Diagnosed with non-CF bronchiectasis by computerised tomography (or high resolution CT) and recorded in the subject’s notes;
4. Had at least 2 NCFB pulmonary exacerbations requiring oral antibiotics or 1 pulmonary exacerbation requiring intravenous antibiotics in the 12 months preceding the Screening Visit (Visit 1);
5. 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);
6. Are clinically stable and have not required a change in pulmonary treatment for at least 30 days before the Screening Visit;
7. Have pre-bronchodilator FEV1 =30% of predicted;
8. Had a positive sputum culture for P. aeruginosa from an adequate sample taken at the Screening Visit (Visit 1).

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 132
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 132

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) or focal endobronchial lesion or otherwise curable causes (e.g. foreign body aspiration);
2. known history of hypogammaglobulinaemia requiring treatment with immunoglobulin, inflammatory bowel disease, primary ciliary dyskinesia, myasthenia gravis, porphyria or myeloproliferative disease, severe cardiovascular disease;
3. a major abdominal, chest or brain surgery in the 3 months prior to Screening Visit (Visit 1) or planned inpatient major surgery during the study period;
4. receiving treatment for allergic bronchopulmonary aspergillosis (ABPA);
5. massive haemoptysis (greater than or equal to 300 mL or requiring blood transfusion) in the preceding 4 weeks before Screening Visit (Visit 1);
6. predominant lung condition being chronic obstructive pulmonary disease (COPD) or asthma or interstitial lung disease in the opinion of the Investigator;
7. History of any of the following:
- listed for transplantation;
- any other significant active illness likely to affect the patient’s survival within 12 months;
- receiving long-term domiciliary oxygen therapy or non-invasive ventilation for the management of respiratory failure;
8. current active malignancy, except for basal cell carcinoma of the skin without metastases, history of solid organ or bone marrow transplant;
9. taking immunosuppressive medications such as azathioprine, methotrexate, ciclosporine, tacrolimus, sirolimus, mycophenolate, anti-cytokine medications, rituximab;
10. known history of human immunodeficiency virus (HIV), hepatitis B or C;
11. current diagnosis of Mycobacterium tuberculosis infection;
12. positive cultures for Mycobacterium abscessus complex, or Mycobacterium avium complex, or Mycobacterium xenopi, or Mycobacterium kansasii, or Mycobacterium malmoense or Mycobacterium simiae in the year preceding the Screening Visit (Visit 1);
13. current treatment for non-tuberculous mycobacterial (NTM) pulmonary infection or be under consideration for NTM treatment in the next 12 months;
14. current smokers or ex-smokers less than 6 months prior to Screening Visit (Visit 1);
15. evidence of bronchial hyperreactivity that may, in the opinion of the Investigator, indicate such subjects will not be able to tolerate colistimethate sodium;
16. known to be intolerant to inhaled beta agonists (bronchodilators);
17. known or suspected to be allergic or unable to tolerate colistimethate sodium or other polymixins;
18. therapy with long term (= 30 days) prednisone at stable dose greater than 15 mg a day (or equivalent dose of any other corticosteroid) prior to Screening Visit 1 (Visit 1);
19. new maintenance treatment with oral macrolides (azithromycin or erythromycin) started within 30 days of the Screening Visit (Visit 1);
20. use of any intravenous or intramuscular or oral or inhaled antipseudomonal antibiotic (except chronic macrolides azithromycin or erythromycin with a stable dose) within 30 days prior to Screening Visit (Visit 1);
21. 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 throughout their involvement in the trial;
22. Significant abnormality in clinical evaluations and/or laboratory tests (physical examination, vital signs, haematology, clinical chemistry, ECG) endang

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

Health Condition(s) or Problem(s) studied

Non-cystic fibrosis bronchiectasis chronically infected with Pseudomonas aeruginosa
MedDRA version: 19.1 Level: PT Classification code 10006445 Term: Bronchiectasis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Intervention(s)

Trade Name: Promixin, 1 million International Units (IU) Powder for Nebuliser Solution
Product Name: Colistimethate sodium
Pharmaceutical Form: Powder for nebuliser solution
INN or Proposed INN: COLISTIMETHATE SODIUM
CAS Number: 8068-28-8
Other descriptive name: Colistimethate Sodium
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 1000000-
Pharmaceutical form of the placebo: Nebuliser solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: To investigate if the use of inhaled Promixin® (colistimethate sodium), administered twice daily for 12 months, delays the time to the first pulmonary exacerbation compared to placebo in subjects with non–cystic fibrosis (CF) bronchiectasis chronically infected with P. aeruginosa.

Primary end point(s): The primary endpoint of this trial is the time (in days) from first dose of IMP until the first NCFB pulmonary exacerbation.

Secondary Objective: Not Applicable

Timepoint(s) of evaluation of this end point: • time to event evaluated during the entire treatment period

Secondary Outcome(s)

Secondary end point(s): Efficacy Endpoints
The secondary efficacy endpoints of this trial are:
• the yearly mean NCFB pulmonary exacerbation rate;
• the number of NCFB pulmonary exacerbations requiring intravenous antibiotics or oral antibiotics;
• the QoL as measured by the total scores of the SGRQ and QOL-B questionnaires;
• the time to first NCFB pulmonary exacerbation (in days) and the yearly mean pulmonary exacerbation rate considering adherent subjects only (adherent subjects are defined as taking at least 80% of the prescribed therapy, according recordings by the I-neb logging system);
• the P. aeruginosa density as determined by the mean change in log10 CFU/g sputum from baseline (Visit 2) to Day 28 of treatment (Visit 3).
• The average number of hospitalizations for pulmonary exacerbations.
• The number of subjects hospitalized for NCFB pulmonary exacerbations;
• The number of days of work absence

Safety Endpoints
The safety endpoints of this trial are:
• the incidence of TEAEs;
• the number of subjects experiencing bronchospasm clinically or spirometrically determined following IMP administration during clinic visit ;
• P. aeruginosa susceptibility to colistin at end of treatment (12 months [Visit 7]).
• Haematology and clinical chemistry;
• Physical examination and vital signs data;
• 12-lead Electrocardiogram.

Timepoint(s) of evaluation of this end point: Efficacy Endpoints
• yearly mean pulmonary exacerbation rate: from baseline to the End of the study
• number of pulmonary exacerbations requiring intravenous antibiotics..: from baseline to the End of the study
• QoL: from baseline (visit 2) to the End of the study
Safety Endpoints
• incidence of TEAEs: from baseline to the End of the study
• the number of subjects experiencing bronchospasm ...: from baseline to the End of the study
• monitoring subjects’ lung function: over the duration of the study by means of presalbutamol
• FEV1 and FVC measurements & physical/vital signs data: from baseline to the End of the study
• P. aeruginosa susceptibility to colistin: at End of the study
• Haematology, clinical chemistry & 12-ECG: at screening vist and at the end of the trial

Secondary ID(s)

Z7224L02

Source(s) of Monetary Support

Zambon SpA

Ethics review

Status: Approved
Approval date: 19/04/2017
Contact: