The purpose of this study is to examine the efficacy and safety of 26 weeks treatment with inhaled mannitol in subjects with cystic fibrosis. Previous studies have demonstrated improvements in lung function, mucociliary clearance, changes in physical properties of mucus, 24 hour sputum weight and quality of life. The results of this study are to further investigate and confirm these findings in addition to examine the effect on antibiotic use and chest infections. It is hypothesised that inhaled mannitol will have beneficial effects compared to a control treatment. An open label phase of 26 weeks duration will follow the blinded 26 week phase. During the open label phase all subjects will receive active treatment.

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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