Please select the eligibility criteria that correspond to the clinical trial below.
Title: Long Term Administration of Inhaled Dry Powder Mannitol In Cystic Fibrosis - A Safety and Efficacy Study
Brief Summary: The purpose of this study is to determine the efficacy and safety of chronic treatment with inhaled dry powder mannitol in subjects with cystic fibrosis. Previous studies have demonstrated an improvement in lung function related to small airways obstruction and a significant improvement in respiratory symptoms and quality of life after a 2 week treatment with mannitol. This current study seeks to support these early findings and to extend the evidence to support its use as a mucoactive therapy in cystic fibrosis. In particular, the hypothesis that enhanced mucus clearance will improve the lung function and clinical presentation in this population, will be investigated. We also hypothesize that enhanced mucociliary clearance will result in a sustained reduction in mucus load, thus providing less opportunity for bacteria to proliferate, affording a reduction in antibiotic use and hospitalizations. The initial 6 month blinded phase will be followed with an additional 6 months of open label treatment.


Options:
A: Inclusion Criteria:

* Male and female patients, \>/= 6 years of age
* Confirmed diagnosis of cystic fibrosis (CF)
* Receiving Pulmozyme once daily chronically for treatment of CF for at least 6 months prior to screening
* Percent predicted FEV1 \>/= 40% at screening based on the Wang (males \< 18 years, females \< 16 years) or Hankinson (males \>/= 18 years, females \>/= 16 years) standardized equations
* Able to reproducibly perform spirometry testing and comply with study assessments

Exclusion Criteria:

* An acute respiratory infection or pulmonary exacerbation within 4 weeks prior to randomization
* Initiation of any new chronic therapy (e.g. inhaled corticosteroids, inhaled oral antibiotics, high-dose ibuprofen, hypertonic saline, ivacaftor) for respiratory disease within 4 weeks prior to randomization
* Changes in chest physiotherapy schedule within 4 weeks prior to randomization
* Hospitalization within 4 weeks prior to randomization
* Planned hospitalization during the 6-week study
* History of organ transplantation
* Participation in an investigational drug or device study within 30 day prior to screening
B: Inclusion Criteria:

1. Have given written informed consent to participate in this study in accordance with local regulations
2. Have a confirmed diagnosis of cystic fibrosis (positive sweat chloride value ≥ 60 mEq/L) and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype)
3. Be aged \> 6 years old
4. Have FEV1 \>40 % and \< 90% predicted
5. Be able to perform all the techniques necessary to measure lung function

Exclusion Criteria:

1. 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.
2. Be considered "terminally ill" or eligible for lung transplantation
3. Have had a lung transplant
4. Be using nebulized hypertonic saline in the 4 weeks prior to visit 1
5. Have had a significant episode of hemoptysis (\>60 mL) in the three months prior to enrolment
6. Have had a myocardial infarction in the three months prior to enrolment
7. Have had a cerebral vascular accident in the three months prior to enrolment
8. Have had major ocular surgery in the three months prior to enrolment
9. Have had major abdominal, chest or brain surgery in the three months prior to enrolment
10. Have a known cerebral, aortic or abdominal aneurysm
11. Be breast feeding or pregnant, or plan to become pregnant while in the study
12. Be using an unreliable form of contraception (female subjects at risk of pregnancy only)
13. Be participating in another investigative drug study, parallel to, or within 4 weeks of visit 0
14. Have a known allergy to mannitol
15. Be using beta blockers
16. Have uncontrolled hypertension - systolic BP \> 190 and / or diastolic BP \> 100
17. Have a condition or be 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
18. Be 'Mannitol Tolerance Test positive'

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C: Inclusion Criteria:

* Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride \> 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
* Informed consent and verbal assent (as appropriate) provided by the subject's parent or legal guardian and the subject
* 6-18 years of age at enrolment and able to perform reproducible spirometry
* Clinically stable at enrolment
* FEV1 % predicted ≥ 80 % as calculated by the Wang reference equations
* Ability to comply with medication use, study visits and study procedures

Exclusion Criteria:

* Respiratory culture positive for NTM or B. cepacia complex within past year or screening
* Use of intravenous antibiotics or oral quinolones within 14 days of screening
* Investigational drug use within 30 days of screening
* Physical findings at screening that would compromise the safety of the participant or the quality of the study data
D: Main Inclusion Criteria:

* Written informed consent
* Confirmed diagnosis of cystic fibrosis
* Aged \> 6 years
* FEV1 \>30 % and \< 90% predicted
* Able to perform all the techniques necessary to measure lung function

Main Exclusion Criteria:

* "Terminally ill" or listed for lung transplantation
* Had a lung transplant
* Using nebulised hypertonic saline
* Significant episode of haemoptysis (\>60 mL) in the three months prior to enrolment
* Recent myocardial infarction or cerebral vascular accident
* Breast feeding or pregnant, or plan to become pregnant while in the study participating in another investigative drug study, parallel to, or within 4 weeks of study entry
* Allergy or intolerance to mannitol
* Using beta blockers
* Have a condition or be 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

Answer: D