Effect of Lucinactant on Mucus Clearance in Cystic Fibrosis Lung Disease

Study Overview
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Brief Summary
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Mucus clearance is impaired in cystic fibrosis. Inhaled surfactants may reduce adhesive forces between mucus and airway surfaces and improve mucus clearance. This in turn my improve lung health. The investigators propose to measure mucus clearance before and after lucinactant or vehicle administration in patients with cystic fibrosis.

Detailed Description
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This single-center pilot study is designed as a double-blind, randomized, cross-over clinical trial to evaluate the effects of inhaled lucinactant, an investigational peptide-containing synthetic surfactant (6 ml of 20 mg total phospholipid (TPL)/mL solution x 5 doses) in patients with mild to moderate CF lung disease. Lucinactant and vehicle will be delivered via a 510k approved vibrating mesh nebulizer, the Pari eFlowTM. The study duration corresponds to a 2-10 day screening phase, followed by a 20 day post-randomization phase that consists of two treatment periods (3 days each) and a washout period (14 days). A total of 16 patients will be enrolled and randomly assigned to one of two treatment sequences (Lucinactant followed by vehicle or vehicle followed by lucinactant). The primary outcome will be the rate of MC, as assessed via gamma scintigraphy, post-lucinactant and post vehicle. Secondary outcomes will include the rate of cough clearance (CC), lung clearance index (LCI), absolute change from baseline in FEV1 after 5 doses of study medication, CF-specific quality of life score (via CFQ-R instrument), in vitro assessments of sputum rheology, and various safety parameters.

Official Title
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A Double Blind, Cross-Over Study Comparing Aerosolized Lucinactant and Vehicle on Mucociliary Clearance for Cystic Fibrosis Lung Disease

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Lucinactant first
* Drug: Placebo first


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cystic fibrosis FEV1>40% Exclusion Criteria: Unstable lung disease Unable or unwilling to stop hypertonic saline and dornase alfa for 3 days prior to each study period Relevant drug allergy or intolerance Recent investigational drug use (30 days)

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Lucinactant first, then placebo<br>Active treatment first, then washout period, then placebo treatment | Drug: Lucinactant first<br>* lucinactant 120 mg (20 mg/ml) x 5 doses over 24 hours, then washout period x 14 days, then vehicle x 5 doses over 24 hrs<br>* Other names: KL-4 surfactant, lucinactant, aerosurf;|
| Other: Placebo treatment first, then lucinactant treatment<br>0.9% NaCl vehicle treatment first, then washout period, then lucinactant treatment | Drug: Placebo first<br>* 6 mL normal saline x 5 doses over 24 hours, then washout period x 14 days, then lucinactant x 5 doses over 24 hours<br>* Other names: 0.9% NaCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mucociliary Clearance | Clearance of radiolabeled particles, following inhalation, are followed over time. Average clearance rate through 60 minutes post inhaled isotope deposition is calculated. Absolute difference between baseline and post-treatment (e.g. <60 minutes after the last dose of lucinactant or placebo) reported. | 1 hour after final treatment (5th dose) minus baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spirometry | Percent change (relative) in FEV1 between pre-treatment baseline and following 5 doses of study treatment. Post treatment values obtained 3 and approximately 22 hours after 5th dose were averaged to determine the treatment effect. | after 5 doses |