It is hypothesised that inhaled mannitol 400 mg b.d. will lead to a significant improvement in the absolute change in percentage of predicted FEV1 from baseline following eight-weeks of trial treatment compared to treatment with inhaled placebo b.d. Any improvement in FEV1 is considered clinically meaningful; however, this trial has set a threshold of 3% for the purposes of determining an appropriate sample size for statistical power whilst retaining trial feasibility in an orphan disease population.
Drug Name: Dry powder mannitol for inhalation Phase: 2 Indication: Paediatric and adolescent cystic fibrosis Trial Centres: Multicentre Sponsor: Pharmaxis Limited, 20 Rodborough Road, Frenchs Forest, NSW 2086 Australia Trial Duration: 27 weeks Number of Subjects: 160 Trial Design: Randomised, multicentre, double-blind, placebo-controlled, crossover Primary Objective: To determine the effect of eight weeks of twice-daily treatment with inhaled dry powder mannitol on lung function (FEV1) in subjects with CF who are aged six to seventeen years Dosage and Administration: Trial drug is to be administered via a dry powder inhaler. * Mannitol 400 mg b.d. for 8 weeks followed by a 8-week washout followed by placebo b.d. for 8 weeks; or * Placebo b.d. for 8 weeks followed by a 8-week washout followed by mannitol 400 mg b.d. for 8 weeks. Statistical Methods: * The primary and secondary efficacy analyses will be based upon a modified Grizzle model for crossover design. Absolute and relative changes from baseline in percentage of predicted FEV1 and FVC will be analysed. The absolute change in percentage of predicted lung function (FEV1 and FVC) will be the primary focus. Changes in FEF25-75 will also be analysed. * Safety data will be analysed descriptively (listings and summary tables).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
95
Active treatment is inhaled mannitol with a particle size of 3-4 microns
The PLacebo is non respirable mannitol due to the big size particle
John Radcliffe Hospital
Oxford, Oxford, United Kingdom
Effect on lung function (FEV1)
To determine the effect of eight weeks of twice-daily treatment with inhaled dry powder mannitol on lung function (FEV1) in subjects with CF who are aged six to seventeen years.
Time frame: The absolute change from each treatment period baseline to week 8 of each treatment period in percentage of predicted FEV1.
Effect on FVC
To determine the effect of inhaled mannitol on FVC
Time frame: The absolute change from each treatment period baseline to week 8 of each treatment period in percentage of predicted FVC.
Effect of inhaled mannitol on FEF25-75
To determine the effect of inhaled mannitol on FEF25-75 (exploratory endpoint)
Time frame: The absolute change from each treatment period baseline to week 8 of each treatment period in percentage of predicted FEF25-75.
Assess safety
Assessment of safety will be made on the basis of reviewing changes in physical examination and using adverse event data.
Time frame: From each treatment period baseline to week 8 of each treatment period.
Sputum weight
To evaluate the difference in treatment induced sputum weight in subjects treated with inhaled mannitol compared with placebo
Time frame: The absolute change from each treatment period baseline to week 8 of each treatment period in sputum weight.
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