Effect of Lucinactant on Mucus Clearance in Cystic Fibrosis Lung Disease

• Spirometry [ Time Frame: acute and after 5 doses ] [ Designated as safety issue: Yes ]
• Lung clearance index [ Time Frame: baseline and after 5 doses ] [ Designated as safety issue: No ]
• Quality of Life (CFQ-R) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
• Sputum rheology [ Time Frame: After 5 doses ] [ Designated as safety issue: No ]

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.

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.

• 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 Name: KL-4 surfactant, lucinactant, aerosurf
• 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

• Lucinactant first, then placebo
  Active treatment first, then washout period, then placebo treatment
  Intervention: Drug: Lucinactant first
• Placebo treatment first, then lucinactant treatment
  0.9% NaCl vehicle treatment first, then washout period, then lucinactant treatment
  Intervention: Drug: Placebo first

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)

• Cystic Fibrosis Foundation
• Discovery Laboratories