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 is a chronic lung condition in which damage to the
airways causes abnormal dilation of one or more bronchi, leading to
pooling of mucus in affected areas |
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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 | 14.0 |
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 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 analyzed 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 to 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.5.1.1 | Timepoint(s) of evaluation of this end point |
This is a 52 week study and the primary end point will be measured
across the 52 weeks. |
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E.5.2 | Secondary end point(s) |
Efficacy
St George's Respiratory Questionnaire (SGRQ) scores
Courses of; days on; time to need for; oral, IV or inhaled antibiotics
prescribed for worsening respiratory
signs and symptoms related to a treated pulmonary exacerbation
Time to first graded exacerbation; duration of graded exacerbations
24 hour sputum volume
Change in daytime sleepiness scores
Change in FEV1, FVC, FEV1/FVC, FEF25-75 values
(Exploratory) Number of hospitalizations due to pulmonary
exacerbations
Safety
Adverse events
Airway reactivity following a mannitol tolerance test (MTT) (acute
decrease in FEV1 >20%)
Laboratory tests:
Complete blood count; electrolytes; creatinine and blood urea nitrogen;
and liver function tests
Qualitative sputum microbiology: disappearance or appearance of
pathogens
Vital signs and physical examination
Costs, Health Status, Utilities and Cost Effectiveness
Total costs incurred in intervention and placebo control groups
* Costs associated with inhaled mannitol
* Costs of antibiotic use and rescue medication
* Costs of hospitalizations and other secondary care services used
* Cost of primary and community care services used
Results from Health Utilities Index Questionnaire in intervention and
placebo control groups to derive:
* Health status
* Health related quality of life
* Utility scores
* Calculation of quality adjusted life years
Determination of cost-effectiveness ratios for intervention and placebo
control groups
* Sensitivity analysis, to assess extent to which variation in parameter
estimates affect cost effectiveness
ratios
* Analysis on the extent to which variation in parameters affects results
from the Health Utilities Index
Questionnaire |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
This is a 52 week study and the secondary end point will be measured
across the 52 weeks. |
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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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Placebo = sub-therapeutic control |
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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 | 3 |
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 | 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 |
Argentina |
Australia |
Belgium |
Chile |
Germany |
Netherlands |
New Zealand |
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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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 | 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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |