Inhaled Mannitol as a Mucoactive Therapy for Bronchiectasis

Inclusion criteria

• Have given written informed consent to participate in this study in accordance with local regulations
• Have documented evidence of confirmed diagnosis of (non-cystic fibrosis) bronchiectasis by computed tomography (CT), High resolution computed tomography (HRCT) or bronchogram
• Be aged 18 - 85 years inclusive, male and female
• Have FEV1 (Forced expiratory volume in one second) ≥ 40% and ≤85% predicted* and ≥1.0L (*according to NHANES III predicted tables) measured at Visit 0A (V0A)
• Clinician documented history of at least 2 pulmonary exacerbations, each requiring antibiotic therapy, in the last 12 months prior to Visit 0A (V0A) and a total of at least 4 in the last 2 years prior to Visit 0A
• Have a total SGRQ (St George's respiratory questionnaire) score of ≥30 at Visit 0B (V0B)
• Have a production of ≥10g of sputum at Visit 0B Have reported chronic sputum production of ≥1 tablespoon (15mL) per day on the majority of days in the 3 months prior to Visit 0A
• Be able to perform all the techniques necessary to measure lung function
• Have FEV1 ≥40% predicted* and ≥1.0L (*according to NHANES III 1999 predicted tables) measured at V0B (Baseline result prior to MTT (Mannitol Tolerance Test) administration)

Exclusion criteria

• Be investigators, site personnel directly affiliated with this study, or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biologically or legally adopted.
• Have bronchiectasis as a consequence of cystic fibrosis or focal endobronchial lesion or otherwise curable causes (e.g. foreign body aspiration)
• Be considered "terminally ill" or listed for transplantation
• Be using hypertonic saline in the 14 days prior to commencing Visit 0B or thereafter at any time during the study
• Have previously used inhaled mannitol (Bronchitol) for more than a day
• Have had a significant episode of hemoptysis (>60 mL) in the previous 6 months
• Have had rescue antibiotics in the 4 weeks prior to V0B (chronic background antibiotic therapy accepted)
• Have smoked within the last 3 months and must not smoke during their participation in the study
• Have had a myocardial infarction in the three months prior to Visit 0A
• Have had a cerebral vascular accident in the three months prior to Visit 0A
• Have had major ocular surgery in the three months prior to Visit 0A
• Have had major abdominal, chest or brain surgery in the three months prior to Visit 0A
• Have a known cerebral, aortic or abdominal aneurysm
• Have actively treated Mycobacterium tuberculosis
• Have actively treated or unstable nontuberculous mycobacterial (NTM)infection or be under consideration for NTM treatment in the next 12 months
• Have unstable Allergic bronchopulmonary aspergillosis (ABPA) requiring steroid therapy (≤5mg dose oral steroids in stable ABPA accepted)
• Have end stage interstitial lung disease
• Have active malignancy including melanoma (other skin carcinomas exempted). Remissions from any malignancy ≥2 years also exempted
• Be breast feeding or pregnant, or plan to become pregnant while in the study
• Be using an unreliable form of contraception (female subjects at risk of pregnancy only)
• Be participating in another investigational drug study, parallel to, or within 4 weeks of Visit 0A
• Have a known intolerance to mannitol or β2-agonists
• Have uncontrolled hypertension - e.g. for adults: systolic blood pressure (BP) > 190 and or diastolic BP > 100
• Subject has a condition or is in a situation which in the Investigator's opinion may put the subject at significant risk, may confound results or may interfere significantly with the patient's participation in the study
• Have previously been screen failed for the study (exceptions - see section 3.3.2 Eligibility Criteria - Rescreening)