E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-CF bronchiectasis and gram-negative endobronchial infection |
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E.1.1.1 | Medical condition in easily understood language |
Bronchiectasis and specific bacteria in the airways |
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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 | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070295 |
E.1.2 | Term | Infective exacerbation of bronchiectasis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
This study is designed to assess the safety and efficacy of aztreonam for inhalation solution/aztreonam 75 mg powder and solvent for nebuliser solution (AZLI) in subjects with non-CF bronchiectasis and gram negative endobronchial infection. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male/Female not less than 18 years old
• Bronchiectasis confirmed by documented computed tomography (CT) scan within 5 years prior to Visit 1, or by prior approval of the Medical Monitor without intervening lung resection
• Reported chronic sputum production on most days during the 4 weeks prior to Visit 1
• Positive sputum culture for target gram-negative organism(s) at Visit 1
• Documented history of positive sputum culture (or bronchoscopic culture) for a target gram-negative organism OR documented history of treatment with antibiotics with gram-negative coverage for an exacerbation of bronchiectasis within 5 years prior to Visit 1
• Chest X-Ray (CXR) obtained and interpreted at Visit 1 or between Visits 1 and 2, without significant acute findings (e.g., no new infiltrate). With prior approval of the Medical Monitor, a CXR obtained within 10 days prior to Visit 1 may be acceptable for study entry.
• Forced expiratory volume in one second (FEV1) not less than 20% predicted approximately 15 minutes post-bronchodilator at Visit 1
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E.4 | Principal exclusion criteria |
• Hospitalization within 14 days prior to Visit 1
• Reported episode of hemoptysis greater than 30 mL (~2 tablespoons) within 14 days prior to Visit 1, on the day of Visit 1, and from Visit 1 through Visit 2
• Antibiotics to treat respiratory symptoms (excluding chronic, stable treatment with a macrolide) within 14 days prior to Visit 1, on the day of Visit 1, and from Visit 1 through Visit 2
• Change in bronchodilator, inhaled corticosteroid, macrolide, or bronchial hygiene therapies within 28 days prior to Visit 1 and through study completion
• Change in systemic corticosteroid therapy within 28 days prior to Visit 1 and from Visit 1 through Visit 2. After Visit 2, systemic corticosteroid therapy (maximum of 14 days per course) will be allowed to treat worsening respiratory signs and/or symptoms.
• Previous treatment with or exposure to Cayston (AZLI)
• Serious adverse event between Visits 1 and 2
• History of cystic fibrosis (CF)
• Current treatment for nontuberculous mycobacteria (NTM) infection
• Active mycobacterium tuberculosis (MTB) infection within one year prior to Visit 1
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change in the Respiratory Symptoms score on the QOL-B from baseline to the end of placebo-controlled Course 1 (i.e., change from Day 0 [Visit 2] to Day 28 [Visit 4]). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change from Day 0 [Visit 2] to Day 28 [Visit 4] |
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E.5.2 | Secondary end point(s) |
•Change in the Respiratory Symptoms score on the QOL-B at the end of placebo-controlled Course 2 (Day 84 [Visit 6]) compared to baseline (Day 0 [Visit 2])
•Time to Protocol-Defined Exacerbation (PDE) prior to open label AZLI treatment
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Change from Day 0 [Visit 2] to Day 84 [Visit 6]
•Entire time from Day 0 [Visit 2] to Day 112 [Visit 7] |
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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 | No |
E.6.3 | Therapy | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Open label course of study drug for all subjects after the placebo-controlled courses |
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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 | 2 |
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 | 42 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Date of last study visit of last study subject. |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
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 |