A Safety and Efficacy Trial of Inhaled Mannitol in Adult Cystic Fibrosis Subjects
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Inhaled mannitol; Placebo Comparator: Arm B - Control
Intervention description: Inhaled mannitol 400 mg BD for 26 weeks; Placebo Comparator: Arm B - Control BD for 26 weeks
Intervention MeSH terms: Mannitol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 423.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No

Summary:

      This trial aims to provide prospective evidence of the safety and efficacy of mannitol 400 mg
      b.i.d. in subjects aged 18 years and above.

      We hypothesize that inhaled mannitol 400 mg b.i.d. will increase the mean change from
      baseline FEV1 (mL) compared to control over the 26-week treatment period in adult subjects
      with cystic fibrosis. Any improvement in FEV1 is considered clinically meaningful, however,
      this trial has set a threshold of 80 mL for the purposes of determining an appropriate sample
      size for statistical power while retaining trial feasibility in an orphan disease population
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have given written informed consent to participate in this trial 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 at least 18 years old;

          4. Have FEV1 > 40 % and < 90% predicted (using NHanes III [1]);

          5. Be able to perform all the techniques necessary to measure lung function;

          6. Be adherent with maintenance therapies (antibiotics and or rhDNase), if used, for at
             least 80% of the time in the two weeks prior to visit 1 and

          7. If rhDNase and/or maintenance antibiotic are being used treatment must have been
             established at least 1 month prior to screening (Visit 0). The subject should remain
             on the rhDNase and / or maintenance antibiotics for the duration of the trial. The
             subject should not commence treatment with rhDNase or maintenance antibiotics during
             the trial

        Exclusion Criteria:

          1. Be investigators, site personnel directly affiliated with this trial, 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 maintenance nebulized hypertonic saline in the 2 weeks prior to visit 1;

          5. Have had a significant episode of hemoptysis (> 60 mL) in the three months prior to
             Visit 0;

          6. Have had a myocardial infarction in the three months prior to Visit 0;

          7. Have had a cerebral vascular accident in the three months prior to Visit 0;

          8. Have had major ocular surgery in the three months prior to Visit 0;

          9. Have had major abdominal, chest or brain surgery in the three months prior to Visit 0;

         10. Have a known cerebral, aortic or abdominal aneurysm;

         11. Be breast feeding or pregnant, or plan to become pregnant while in the trial;

         12. Be using an unreliable form of contraception (female subjects at risk of pregnancy
             only);

         13. Be participating in another investigative drug trial, parallel to, or within 4 weeks
             of screening (Visit 0);

         14. Have a known allergy to mannitol;

         15. Be using non-selective oral beta blockers;

         16. Have uncontrolled hypertension -i.e. 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 subject's participation in the trial;or

         18. Have a failed or incomplete MTT at trial entry (as evaluated in Section 8.1.1.1).

         19. The subject must not commence treatment with rhDNase or maintenance antibiotics during
             the trial.