E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Bronchiectasis, which is a long-term condition that occurs when the small airways in the lungs become damaged and filled with phlegm, leading to frequent chest infections. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006445 |
E.1.2 | Term | Bronchiectasis |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 evaluate the safety and tolerability of Aztreonam lysine in bronchectasis |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of Aztreonam Lysine on time to first lung infection To determine the effect of Aztreonam lysine on the frequency of lung infections over 12 months To determine the effect of Aztreonam lysine on quality of life To determine the effect of Aztreonam lysine on lung function Bacterial load at the end of the first treatment cycle To determine the impact of Aztreonam lysine on the time to first lung infection, including all clinically treated lung infections To determine whether missing doses of the medicine reduces the effectiveness of the medicine To store blood and sputum samples for future studies into improving the diagnosis and treatment of bronchiectasis To determine the effect of Aztreonam lysine on different types of lung infections that affect people with bronchiectasis
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• ≥ 18 years of age • Able to give informed consent • Clinical diagnosis of Bronchiectasis • CT scan of the chest demonstrating bronchiectasis in 1 or more lobes • A history of at least 3 exacerbations in the previous 12 months • Bronchiectasis severity index score >4 • Pseudomonas aeruginosa or other Gram-negative respiratory pathogen detected in sputum or bronchoalveolar lavage on at least 1 occasion in the previous 12 months. • A sputum sample that is culture positive for P. aeruginosa or other Gram-negative respiratory pathogens sent at the screening visit and within 35 days of randomization. Pre-specified eligible organisms include Eschericia coli, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens, Achromobacter, Enterobacter and Stenotrophomonas maltophilia |
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E.4 | Principal exclusion criteria |
• Participant has cystic fibrosis • Immunodeficiency requiring replacement immunoglobulin. • Active tuberculosis or nontuberculous mycobacterial infection (defined as currently under treatment, or requiring treatment in the opinion of the investigator). • Recent significant haemoptysis (a volume requiring clinical intervention, within the previous 4 weeks). • Treatment with inhaled, systemic or nebulized anti-Pseudomonal antibiotics in the 28 days prior to randomization • Oral macrolides which have been taken for a period of less than 3 months prior to the start of the trial. • Treatment of an exacerbation and receiving antibiotic treatment within 4 weeks of randomization • Primary diagnosis of COPD associated with >20 pack years smoking history. • History of poorly controlled asthma or a history of bronchospasm with inhaled antibiotics. • Pregnant or lactating females. • Participants with FEV1 <30% predicted value at screening. • Previous history of intolerance to Aztreonam or bronchospasm reported with any other inhaled anti-bacterial. • Glomerular filtration rate (eGFR) below 30ml/min/1.73m2 or requiring dialysis. This will be determined at screening. • Use of any investigational drugs within five times of the elimination half-life after the last trial dose or within 30 days, whichever is longer. • Unstable co-morbidities (cardiovascular disease, active malignancy) which in the opinion of the investigator would make participation in the trial not in the participants best interest. • Long term oxygen therapy • Women of child bearing age or male partners of women of child bearing age and not practicing a method of acceptable birth control (see below) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Recording of adverse events, serious adverse events and trial treatment withdrawals between groups |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Reported at any time point in the trial. |
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E.5.2 | Secondary end point(s) |
1 Time to first exacerbation 2 Frequency of exacerbations 3 St. Georges Respiratory Questionnaire, Quality of Life Bronchiectasis Questionnaire, Bronchiectasis Health Questionnaire 4 FEV1 5 CFU/ml 6 Time to first exacerbation (protocol defined and non-protocol defined) 7 Compliance recorded and repeat measurement of efficacy end-points in those complying with >80% of doses 8 Biomarker measurement, Microbiome studies, Antibiotic resistance studies 9 Exacerbations subtyped into those associated with viruses, new bacteria or non-infectious exacerbations
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 Single event per participant over 12 months 2 Count data over 12 months 3 Continuous variables at 0, 1, 3, 6, and 12 months 4 Continuous variables at 0, 1, 3, 6, and 12 months 5 Baseline and end of 28 days 6 Up to 12 months 7 Compliance assessments at all trial visits 8 Future work 9 Count data over 12 months
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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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Database lock. We allow time after last patient last visit for final sample analysis, data verification and data cleaning prior to database lock. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 30 |