E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-CF bronchiectasis (CF = cystic fibrosis) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006445 |
E.1.2 | Term | Bronchiectasis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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-CF bronchiectasis infected with P. aeruginosa susceptible to Promixin. |
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E.2.2 | Secondary objectives of the trial |
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. 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 as detected by a reduced forced expiratory volume in 1 second (FEV1) following inhalation of the Promixin compared to vehicle. 7. To assess the severity of exacerbation (requires intravenous antibiotics = severe / requires oral antibiotics = moderate). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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). |
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E.4 | Principal 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 or myloproliferative disease. 3. Confirmed, recent, active allergic bronchopulmonary aspergillosis (ABPA). 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 have HIV, hepatitis B or hepatitis C. 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. 9. Known on history, to have received prophylactic inhaled colistimethate sodium prior to screening. (Note: Previous use of other inhaled anti-pseudomonal antibiotics, such as gentamycin and/or tobramycin, does not exclude a patient from the study) 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. New maintenance azithromycin therapy started with in 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: 17. Use of inhaled antibiotics since screening. 18. A ≥15% fall in FEV1 in the 30 minutes after receiving the first dose of IMP. 19. Haematology and biochemistry test results make the patient unsuitable for the study in the opinion of the investigator. |
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E.5 End points |
E.5.1 | 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 ♦ Increased 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 The start of the exacerbation will be taken as the first day that the defining symptoms occurred. The treatment of exacerbations will follow current treatment regimens used in the participating hospital. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is defined as completion of the trial procedures defined in the protocol by all participants (e.g. last follow-up visit or questionnaire) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |