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: 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
B: Inclusion Criteria:

1. Confirmed diagnosis of cystic fibrosis (sweat test/genotype)
2. Aged 8 years or older
3. Have FEV1 between 40% and 80% of predicted for height, age and gender OR a decrease in FEV1 of 20% or more than that recorded 6-12 months previously.
4. As determined by the investigator, are capable and willing to

   * Use the study diary as required for this protocol
   * Able to perform all of the techniques necessary to measure lung function
   * Able to administer the dry powder mannitol
5. Are capable of and have given informed consent
6. Clinically stable at study entry

Exclusion Criteria:

1. Investigators, site personnel directly affiliated with this study, and their immediate families.
2. Subjects under the age of 8 years.
3. Subjects with currently active asthma
4. Subjects using hypertonic saline treatment in the last 2 weeks
5. Considered "terminally ill" or listed for transplantation
6. Requiring home oxygen or assisted ventilation
7. Colonisation with Burkholderia cepacia
8. Significant episode of hemoptysis (\>60 mls) in the previous 12 months
9. Myocardial Infarction in the six months prior to enrolment.
10. Cerebral Vascular Accident in the six months prior to enrolment.
11. Ocular surgery in the three months prior to enrolment.
12. Abdominal surgery in the three months prior to enrolment.
13. Subjects who are breast feeding or pregnant.
14. Female subjects of reproductive capability, not using a reliable form of contraception
15. Inability to obtain informed consent from the subject or subject's authorised representative.
16. Subjects who have participated in another investigative drug study parallel to, or within 4 weeks of study entry.
17. Known intolerance to mannitol or beta2 agonists.
18. Uncontrolled hypertension - systolic BP \> 160 and or diastoli
C: 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
D: Inclusion Criteria:

* Diagnosis of CF.
* Age ≥ 12 years at the Screening Visit.
* Forced expiratory volume in 1 second (FEV1) ≥ 70 % predicted at the Screening Visit if \< 18 years old, and ≥ 60 % predicted at Screening Visit if ≥ 18 years old.
* Clinically stable with no significant changes in health status within the 7 days prior to and including the Screening Visit.
* Current treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for at least the 90 days prior to and including the Screening Visit and willing to continue daily use for the duration of the study.
* Currently taking hypertonic saline (at least 3%) and/or dornase alfa for at least the 90 days prior to and including the Screening Visit and willing to continue daily use for the 2-week screening period.

Exclusion Criteria:

* Active smoking or vaping.
* Use of an investigational drug within 28 days prior to and including the Screening Visit.
* Changes to chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin, aztreonam lysine) within 28 days prior to and including the Screening Visit. This includes new airway clearance routines.
* Acute use of antibiotics (oral, inhaled or IV) or acute use of systemic corticosteroids for respiratory tract symptoms within 7 days prior to and including the Screening Visit.
* Chronic use of systemic corticosteroids at a dose equivalent to ≥ 10mg per day of prednisone within 28 days prior to and including the Screening Visit.
* Antibiotic treatment for nontuberculous mycobacteria (NTM) within 28 days prior to and including the Screening Visit.

Answer: A