The Safety, Tolerability, PK and PD of GSK2339345 in Healthy Subjects
Condition: Cough
MeSH terms: Cough
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a First Time in Human (FTIH) study for the sodium channel inhibitor, GSK2339345. The
      study is split into two parts. Part A will assess the safety and tolerability of the new
      drug. Part B will assess safety and tolerability as well as the effect of GSK2339345 on
      induced cough.
    

Detailed description: 
      The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and
      pharmacodynamic (PD) 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.

      Part A of this study will be conducted in healthy volunteers to investigate the safety and
      tolerability of GSK2339345, in particular examining oropharyngeal sensation perturbation.
      Part A is an open label, oral, single-dose escalating rinse, gargle and spit study.
      Assessments of sensate changes will include 4 point scale, assessment of sensation on base of
      tongue, sensation of temperature, assessment of taste, a water swallow test and assessment of
      potential paraesthesias. Part A will also include PK assessments to investigate the PK
      profile of GSK2339345.

      Part B of this study is a randomised, double blind, placebo controlled, inhaled dose
      escalation study over two study days per dose to examine the possible adverse events such as
      transient mouth, throat and upper airway numbness in healthy volunteers. Similar assessments
      of sensations to those used in Part A will be performed. The potential for systemic
      cardiovascular (CV) or central nervous system (CNS) effects will also be assessed.
      Pharmacodynamic effects of GSK2339345 will be investigated in Part B using a capsaicin cough
      challenge. The study will investigate whether GSK2339345 can alter the capsaicin cough
      threshold (as determined by the capsaicin concentration required to induce 2 or more (C2) and
      5 or more (C5) coughs) in healthy volunteers. Part B will also include PK assessments to
      investigate the PK profile of GSK2339345. Placebo will be used as a control and nebulised
      lidocaine will be used for control and blinding purposes only.
    

Intervention name(s): GSK2339345 (solution); GSK2339345 (nebulised); Placebo (0.9% sodium chloride solution); Lidocaine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 3, 6, 15, 30, 60 and 120 micrograms (proposed doses). 2 alternating cohorts of 6 subjects. Each subject to receive 3 ascending doses with washout of at least 48 hours between doses. Rinse, Gargle and Spit.; 25, 100, 250, 1000 and 2000 micrograms (proposed doses). Subjects randomised to receive three ascending doses (with each dose given on two consecutive days). Washout of at least 6 days between treatment periods. Nebulised.; Administered on Day 1 of one of the treatment periods in part B. Randomised. Nebulised.; 40mg dose. Administered on Day 2 of one of the treatment periods in part B. Randomised. Nebulised.
Intervention MeSH terms: Lidocaine; Pharmaceutical Solutions
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Capsaicin Challenge; Pharmacodynamics; Safety; Pharmacokinetics; Oral GSK2339345; Tolerability; FTIH; Chronic Cough