Effect of Lucinactant on Mucus Clearance in Cystic Fibrosis Lung Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Lucinactant first; Drug: Placebo first

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Lucinactant first, then placebo; Active treatment first, then washout period, then placebo treatment	Drug: Lucinactant first; 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; Other Names: KL-4 surfactant, lucinactant, aerosurf
OTHER: Placebo treatment first, then lucinactant treatment; 0.9% NaCl vehicle treatment first, then washout period, then lucinactant treatment	Drug: Placebo first; 6 mL normal saline x 5 doses over 24 hours, then washout period x 14 days, then lucinactant x 5 doses over 24 hours; Other Names: normal saline; 0.9% NaCl

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Windtree Therapeutics; Cystic Fibrosis Foundation

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (ACTUAL): August 1, 2010
• Study Completion (ACTUAL): August 1, 2010

Study Registration Dates

• First Submitted: July 6, 2009
• First Submitted That Met QC Criteria: July 7, 2009
• First Posted (ESTIMATE): July 8, 2009

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2017
• Last Update Submitted That Met QC Criteria: January 31, 2017
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Lung Diseases; Pulmonary Fibrosis; Cystic Fibrosis; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: 08-0795; KL4-CF-01; DONALD04A0