E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 difference in the rates of graded pulmonary exacerbations, in patients with bronchiectasis treated with inhaled mannitol compared to placebo control. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the difference in: -Quality of Life as measured by the St. Georges Respiratory Questionnaire (SGRQ). -Antibiotic use prescribed for treated pulmonary exacerbations. Such antibiotic use parameters to be ananlyzed will include number of discrete courses; days on antibiotics; and time to antibiotic need. -Sputum volume. -Daytime sleepiness scores. -Lung functions (FEV1, FVC, FEV1/FVC. FEF25-75 values). -(Exploratory) to investigate the difference in the number of hospitalisations due to pulmonary exacerbations. To evaluate the difference in other graded exacerbation parameters (time to first exacerbation and duration of exacerbation). To monitor the safety profile of inhaled mannitol compared with placebo control in subjects with bronchiectasis by investigating adverse events, airway reactivity, hematology, clinical chemistry, sputum microbiology and vital signs. To compare health status and utility scores (cost effectiveness). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written informed consent. Documented evidence of confirmed diagnosis of bronchiectasis. Aged 18 to 85 years inclusive. FEV1 >= 40% and <= 85% predicted and >= 1.0L. Clinician documented history of at least 2 exacerbations requiring antibiotic treatment, in the 12 months prior to study, and at least 4 in 2 years prior to study. SGRQ score >= 30 24 hour sputum production >=10g Chronic sputum production >= 15mL per day on majority of days in 3 months prior to study. Ability to perform techniques necessary to measure lung function. |
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E.4 | Principal exclusion criteria |
Investigators, site personnel directly affiliated with the study, or immediate families. Bronchiectasis as a result of cystic fibrosis, focal endobronchial lesion or otherwise curable causes. Terminally ill or listed for transplantation, end stage interstitial lung disease. Use of hypertonic saline in the 14 days before, or use during study. Any previous use of mannitol for more than one day. Significant episode of haemoptysis (>60mL) in the 6 months prior to study. Rescue antibiotics in the 4 weeks prior to study. Any of the following in the 3 months prior to study: smoking; myocardial infarction;cerebral vascular accident; major ocular, abdominal, chest or brain surgery. Known cerebral, aortic or abdominal aneurysm. Actively treated mycobacterium tuberculosis or non active infection requiring treatment. Unstable ABPA requiring steroid therapy. Active malignancy. Breast feeding or pregnant or planning to become pregnant or using unreliable contraception. Participation in another study. Known intolerance to mannitol or B agonists. Uncontrolled hypertension. Any condition deemed by the Investigator to put the patient at risk or seriously confound the study result. Previous screen failure for this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Pulmonary exacerbation rates (graded exacerbations). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Placebo = sub therapeutic control |
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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 | 23 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 |
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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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |