non-CF bronchiectasis (CF = cystic fibrosis) MedDRA version: 14.0 Level: PT Classification code 10006445 Term: Bronchiectasis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Promixin 1 million International Units (IU) Powder for Nebuliser Solution
Pharmaceutical Form: Powder for nebuliser solution
Other descriptive name: colistimethate sodium
Concentration un
Sponsors
Profile Pharma Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: At Screening (Visit 1) 1. Aged 18 years and over. 2. Have had P. aeruginosa grown from their sputum at least twice in the 12 months preceding the screening visit. 3. Be within 21 days of completing a course of anti-pseudomonal antibiotics for the successful treatment of an exacerbation. 4. Able and willing to give informed consent, following a detailed explanation of participation in the protocol and signed consent obtained. 5. Diagnosed with non-CF bronchiectasis by computerised tomography (CT) and recorded in the patient’s notes. At Randomisation/Baseline (Visit 2) 6. P. aeruginosa grown from patients’ sputa taken at Visit 1 (Screening). 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: At Screening (Visit 1) 1. Known, on history, to have cystic fibrosis (CF). 2. Known, on history, to have hypogammaglobulinaemia, inflammatory bowel disease, primary ciliary dyskinesia, myasthenia gravis and myloproliferative disease. 3. Confirmed, recent, active ABPA (allergic bronchopulmonary aspergillosis) 4. Significant immune suppression that would interfere with the interpretation of the study e.g. current active malignancy requiring treatment, post solid organ or bone marrow transplant. 5. Known, on history, to be HIV, Hepatitis B or C positive 6. Evidence of bronchoreactivity that may, in the opinion of the investigator, indicate that such patients will not be able to tolerate colistimethate sodium. 7. Not able to tolerate inhaled beta agonists. 8. Allergic to or unable to tolerate colistimethate sodium or other polymixins 9. Known, on history, to have received prophylactic inhaled colistimethate sodium prior to screening 10. Requiring therapy with steroids excepting a stable dose of 15 mg a day or less. 11. Taking anti tumour necrosis factor alpha products. 12. Taking chronic azithromycin therapy started within 6 months of visit 1. 13. Taking hypertonic saline 14. Pregnant or breast feeding or who plan to become pregnant over the next year or of child bearing potential and unwilling to use a reliable method of contraception (oral contraceptive pills (OCP) or barrier methods with a spermicidal preparation) throughout their involvement in the study. 15. In the opinion of the investigator are not suitable for inclusion for whatever reason. 16. Do not have access to a telephone for telephone contacts. At Randomisation/Baseline (Visit 2) patients who satisfy one or more of the following criteria will be withdrawn: 1. Use of inhaled antibiotics since screening. 2. A =15% fall in FEV1 within 30 minutes of receiving the first dose of IMP. 3. Haematology and biochemistry test results make the patient unsuitable for the study in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that inhaled Promixin, administered twice a day for up to 6 months, at a concentration of 1 MIU/mL via an I-neb with a 0.3 mL metering chamber, increases the time to a pulmonary exacerbation, compared to vehicle, in patients with non-cystic fibrosis bronchiectasis infected with P. aeruginosa susceptible to Promixin.;Secondary Objective: 1. To assess the safety of Promixin when administered for 6 months to patients with non-CF bronchiectasis infected with P. aeruginosa susceptible to Promixin compared to vehicle. 2. To assess the effect of Promixin on the weight of sputum produced in 24 hours compared to vehicle. 3. To assess the impact of Promixin on symptoms by means of the St. George’s Respiratory Questionnaire (SGRQ) compared to vehicle. 4. To assess the effect of inhaled Promixin on the flora of sputum and to quantify the effect on P. aeruginosa density compared to vehicle. 5. To assess patients’ compliance with the I-neb system and to explore if there is a correlation between compliance and outcome. 6. To assess the incidence of bronchospasm following inhalation of the Promixin compared to vehicle. 7. To assess the severity of exacerbation (requires intravenous antibiotics = severe / requires oral antibiotics = moderate). ;Primary end point(s): The time (in days), from Baseline/Visit 2 (first dose) for each individual patient, until he/she experiences an exacerbation. An exacerbation is defined as: •Presence of at least 3 of the following 8 signs or symptoms present for at least 24 hours: • Increased cough • Increased amount of sputum produced • Increased sputum purulence • haemoptysis • Increased dyspnoea • Icreased wheezing • Fever (temperature =38°C) • Malaise Plus: • It is clinically determined that the patient requires antibiotic therapy. Antibiotic therapy for exacerbations will be divided into those treated with: • oral antibiotics • intravenous antibiotics ;Timepoint(s) of evaluation of this end point: This stud | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Endpoints 1. Number of adverse events (AEs) reported. 2. Number of patients experiencing a =15% reduction in FEV1 in the 30 minutes post the first dose. 3. Number of serious AEs (SAEs) reported. 4. Number of suspected unexpected serious adverse reactions (SUSARs) reported. 5. Number of patients withdrawing due to AEs. 6. Incidence of strains of P. aeruginosa resistant to Promixin. Efficacy Endpoints 1. The difference in the weight in grams, of sputum expectorated in the 24 hours prior to Visits 2 and 3. 2. The qualitative flora of sputum, the quantification of the P. aeruginosa density as determined by the CFU count and the P. aeruginosa susceptibility to colistimethate sodium. 3. The difference in the total scores on the SGRQ to cover the inter-visit period. 4. The data collected by the “logging system” in the I-neb, that records information on the doses taken will be collected and used to determine compliance and explore if there is a correlation between compliance and outcome. ;Timepoint(s) of evaluation of this end point: The end of the study | — |
Countries
Ireland, Russian Federation, Ukraine, United Kingdom
Contacts
Public ContactRob Kenyon
Profile Pharma Ltd
Outcome results
None listed