This is a study of the sodium channel inhibitor, GSK2339345. Cohort 1 will assess the safety, tolerability and PK of single ascending doses of GSK2339345 administered via an aqueous droplet inhaler in healthy subjects. Cohort 2 will assess the safety, tolerability, and PK of repeat doses of GSK2339345 administered four times a day for two consecutive days via an aqueous droplet inhaler.
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics (PK) effects of GSK2339345 in healthy subjects. GSK2339345 is a blocker of neuronal voltage gated sodium channels in development for the treatment of chronic cough, excessive cough and post-viral and viral (acute) cough. Inhaled pan NaV inhibitors are associated with oropharyngeal sensation perturbation and so this study will establish the potential local sensate effects of GSK2339345 at multiples of the predicted inhaled therapeutic dose. This study also aims to define the maximum tolerated dose of GSK2339345 administered via an aqueous droplet inhaler. Cohort 1 is a randomised, double-blind, placebo-controlled, cross-over, inhaled single-dose escalating study using an aqueous droplet inhaler. Cohort 1 will include assessments of sensate changes via a 4 point scale, assessment of taste via an 11 point scale, and PK assessments to investigate the PK profile of GSK2339345. Cohort 2 of this study is a randomised, double blind, placebo controlled, parallel group, inhaled repeat dose study using a aqueous droplet inhaler. Subjects will be randomised to receive 2000 microgram of GSK2339345 or placebo four times a day for two consecutive study days. Similar assessments of sensations to those used in Cohort 1 will be performed. The potential for systemic cardiovascular (CV) or central nervous system (CNS) effects will also be assessed throughout the study via observation. Cohort 2 will also include PK assessments to investigate the PK profile of GSK2339345. Placebo will be used throughout the study as a control.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
36
250, 1000 and 2000 microgram (proposed doses)
Inhaled 0.9% sodium chloride solution
2000 microgram (proposed dose) administered 4 times a day for two consecutive days
GSK Investigational Site
London, United Kingdom
Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology, clinical biochemistry and cardiac troponin.
To assess the safety and tolerability of single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler.
Time frame: Approximately 5 weeks from first dose to the follow-up visit.
Assessment of oropharyngeal sensation perturbation via a 4 point scale.
To assess the changes in oropharyngeal sensation caused by single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler.
Time frame: Approximately 5 weeks from first dose to the follow-up visit.
Plasma concentrations of GSK2339345 and single and repeat dose derived pharmacokinetic parameters including Cmax, tmax, AUC(0-t), AUC(0-inf), and AUC(0- τ), as appropriate where data allow.
To evaluate the systemic pharmacokinetics of single and repeat doses of inhaled GSK2339345 in healthy volunteers administered by an aqueous droplet inhaler.
Time frame: Approximately 5 weeks from first dose to the follow-up visit.
Identification of taste of the solution and rating on 11 point scale to rate pleasantness or unpleasantness
To assess the palatability of GSK2339345 administered by an aqueous droplet inhaler
Time frame: Approximately 5 weeks from first dose to the follow-up visit.
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Inhaled 0.9% sodium cholride solution