Inhaled Mannitol as a Mucoactive Therapy for Bronchiectasis

• Status: Completed
• Trial end date: 2014-01-01
• Target enrollment: 0
• Participant gender: All

Summary

No gold standard therapy exists for clearing mucus from the airways of patients with bronchiectasis. While rhDNase has a proven place in the treatment of cystic fibrosis (CF), it failed to improve Forced expiratory volume in one second (FEV1) in a short-term non-CF bronchiectasis study and has been shown to be detrimental after 6 months therapy in non CF bronchiectasis, moreover it has no proven effect on mucociliary clearance. Hypertonic saline has been shown to have a comparable mode of action to inhaled mannitol, but has yet to be examined as a long term treatment option in bronchiectasis.

The purpose of this study is to examine the efficacy and safety of 52 weeks treatment with inhaled mannitol in subjects with non-cystic fibrosis bronchiectasis. Previous studies with inhaled mannitol have demonstrated improvement in mucociliary clearance; mucus rehydration; improvement in quality of life and respiratory symptoms in patients with bronchiectasis and pulmonary function in cystic fibrosis. The results of this current study in combination with a recently completed 3 month study seek to confirm these early findings and to extend the evidence to support its use as a mucoactive therapy in subjects with bronchiectasis.

We hypothesize that mannitol will improve the overall health and hygiene of the lung through regular and effective clearing of the mucus load. As a consequence of the reduction in mucus load and inflammatory process, the frequency of bronchiectasis related pulmonary exacerbations and the need for exacerbation related antibiotic treatment should fall. Days in hospital and community health care costs are expected to change in line with improvements in respiratory health.

Finally, we plan to demonstrate that inhaled mannitol is safe and well tolerated over a 52 week period. We will test these hypotheses using 400 mg mannitol twice daily (BD) against control.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pharmaxis
• Treatments: Mannitol

Criteria

Inclusion Criteria

1. Have given written informed consent to participate in this study in accordance with local regulations

2. Have documented evidence of confirmed diagnosis of (non-cystic fibrosis) bronchiectasis by computed tomography (CT), High resolution computed tomography (HRCT) or bronchogram

3. Be aged 18 - 85 years inclusive, male and female

4. 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)

5. 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

6. Have a total SGRQ (St George's respiratory questionnaire) score of ≥30 at Visit 0B (V0B)

7. 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

8. Be able to perform all the techniques necessary to measure lung function

9. 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

1. 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.

2. Have bronchiectasis as a consequence of cystic fibrosis or focal endobronchial lesion or otherwise curable causes (e.g. foreign body aspiration)

3. Be considered "terminally ill" or listed for transplantation

4. Be using hypertonic saline in the 14 days prior to commencing Visit 0B or thereafter at any time during the study

5. Have previously used inhaled mannitol (Bronchitol) for more than a day

6. Have had a significant episode of hemoptysis (>60 mL) in the previous 6 months

7. Have had rescue antibiotics in the 4 weeks prior to V0B (chronic background antibiotic therapy accepted)

8. Have smoked within the last 3 months and must not smoke during their participation in the study

9. Have had a myocardial infarction in the three months prior to Visit 0A

10. Have had a cerebral vascular accident in the three months prior to Visit 0A

11. Have had major ocular surgery in the three months prior to Visit 0A

12. Have had major abdominal, chest or brain surgery in the three months prior to Visit 0A

13. Have a known cerebral, aortic or abdominal aneurysm

14. Have actively treated Mycobacterium tuberculosis

15. Have actively treated or unstable nontuberculous mycobacterial (NTM)infection or be under consideration for NTM treatment in the next 12 months

16. Have unstable Allergic bronchopulmonary aspergillosis (ABPA) requiring steroid therapy (≤5mg dose oral steroids in stable ABPA accepted)

17. Have end stage interstitial lung disease

18. Have active malignancy including melanoma (other skin carcinomas exempted). Remissions from any malignancy ≥2 years also exempted

19. Be breast feeding or pregnant, or plan to become pregnant while in the study

20. Be using an unreliable form of contraception (female subjects at risk of pregnancy only)

21. Be participating in another investigational drug study, parallel to, or within 4 weeks of Visit 0A

22. Have a known intolerance to mannitol or β2-agonists

23. Have uncontrolled hypertension - e.g. for adults: systolic blood pressure (BP) > 190 and or diastolic BP > 100

24. 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

25. Have previously been screen failed for the study (exceptions - see section 3.3.2 Eligibility Criteria - Rescreening)