Long Term Administration of Inhaled Dry Powder Mannitol In Cystic Fibrosis - A Safety and Efficacy Study

Sponsor

Pharmaxis (Industry)

Overall Status

Completed

CT.gov ID

NCT00446680

Collaborator

(none)

340

Enrollment

Locations

Arms

Duration (Months)

11.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Mannitol Drug: placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

340 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Long Term Administration of Inhaled Dry Powder Mannitol In Cystic Fibrosis - A Safety and Efficacy Study

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

May 1, 2010

Actual Study Completion Date :

May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Mannitol 400mg BD for 6 months followed by a 6 month open label period
Placebo Comparator: 2	Drug: placebo placebo BD for 6 months

Arm

Intervention/Treatment

Experimental: 1

Drug: Mannitol

400mg BD for 6 months followed by a 6 month open label period

Placebo Comparator: 2

Drug: placebo

placebo BD for 6 months

Outcome Measures

Primary Outcome Measures

To determine the effects of 400 mg twice-daily administration of IDPM on FEV1 in patients with CF compared to control [6 months]

Secondary Outcome Measures

To determine the effects of 400 mg twice-daily administration of IDPM on FEV1 in patients with CF on existing RhDNase treatment compared to control. (key objective) [6 months]
Reduces pulmonary exacerbations in those taking RhDNase as a sub-group and in the total cohort (key objective) [6 months / 12 months]
Improves quality of life (key objective) [6 months]
Reduces days on IV antibiotics, rescue oral or inhaled antibiotics [6 months / 12 months]
Reduces days in hospital due to pulmonary exacerbations [6 months / 12 months]
Improves other measures of lung function [6 months]
Demonstrates an appropriate safety profile (adverse events, haematology, biochemistry, change in bronchodilator response, sputum microbiology, physical examination) [6 months / 12 months]
Reduces hospital and community care costs [6 months / 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital at Westmead	Sydney	New South Wales	Australia	2145
2	Sydney Childrens Hospital	Sydney	New South Wales	Australia
3	Royal Brisbane Children's Hospital	Brisbane	Queensland	Australia	4029
4	The Prince Charles Hospital	Brisbane	Queensland	Australia	4032
5	Royal Adelaide Hospital	Adelaide	South Australia	Australia
6	Royal Childrens Hospital	Melbourne	Victoria	Australia	3052
7	Beaumont Hospital	Dublin		Ireland
8	National Children's Hospital	Dublin		Ireland
9	Our Lady's Hospital for Sick Children	Dublin		Ireland
10	St Vincent's University Hospital	Dublin		Ireland
11	Alder Hey Children's Hospital	West Derby	Liverpool	United Kingdom
12	Belfast City Hospital	Belfast	Northern Ireland	United Kingdom	BT9 7AB
13	Children's Hospital for Wales	Cardiff	Wales	United Kingdom	CF14 4XW
14	Llandough Hospital	Cardiff	Wales	United Kingdom	CF64 2XX
15	Birmingham Children's Hospital	Birmingham		United Kingdom
16	Birmingham Heartlands Hospital	Birmingham		United Kingdom
17	Bristol Royal Hospital for Children	Bristol		United Kingdom
18	Bristol Royal Infirmary	Bristol		United Kingdom
19	Addenbrooke's Hospital	Cambridge		United Kingdom
20	Papworth Hospital	Cambridge		United Kingdom
21	Seacroft Hospital	Leeds		United Kingdom
22	Cardiothoracic Centre	Liverpool		United Kingdom	L14 3PE
23	The London Chest Hospital	London		United Kingdom	E2 9JX
24	Freeman Hospital	Newcastle		United Kingdom	NE7 7DN
25	Norfolk and Norwich University Hospital	Norwich		United Kingdom	NR4 7UY
26	Nottingham City Hospital	Nottingham		United Kingdom
27	Northern General Hospital	Sheffield		United Kingdom
28	Sheffield Children's Hospital	Sheffield		United Kingdom
29	Southampton General Hospital	Southampton		United Kingdom

Sponsors and Collaborators

Pharmaxis

Investigators

Study Director: Brett Charlton, MBBS, Pharmaxis Ltd Australia
Principal Investigator: Dr Diana Bilton, Papworth Hospital Cambridge, UK
Principal Investigator: Dr Philip Robinson, Royal Children's Hospital, Melbourne, Australia