The Safety, Tolerability, PK and PD of GSK2339345 in Healthy Subjects (FTIH)
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.
Drug: GSK2339345 (solution)
Drug: GSK2339345 (nebulised)
Drug: Placebo (0.9% sodium chloride solution)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Two Part Study to Investigate the Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2339345 in Healthy Subjects. Part A: an Open Label, Dose Escalating, Rinse, Gargle and Spit Study. Part B: a Randomised, Double-blind, Placebo Controlled, Inhaled Dose Escalating Study Using Nebulised Lidocaine for Blinding Purposes.|
- Change in oropharyngeal sensation [ Time Frame: Dosing to 1 hour post dose ] [ Designated as safety issue: Yes ]Measured by 4 point scale, fingertip electrode assessment, sensation to water temperature, adverse events, water swallow test and assessment of gag reflex
- Adverse events (AEs) for all study participants [ Time Frame: Dosing to 24 hours post dose ] [ Designated as safety issue: Yes ]Measurement of types of AEs reported, severity and relationship to study drug
- Assessment of vital signs for all study participants [ Time Frame: Screening to follow-up ] [ Designated as safety issue: Yes ]Triplicate measurements will be taken at screening and pre-dose, single measurements at all other timepoints
- Holter ECG measurement for all study participants [ Time Frame: Screening (Part A and Part B) ] [ Designated as safety issue: Yes ]24 hour Holter ECG will be taken at screening
- 12-lead ECG measurements for all study participants [ Time Frame: Screening to follow-up ] [ Designated as safety issue: Yes ]Triplicate measurements will be taken at screening and pre-dose, single measurements at all other timepoints
- Body temperature for all study participants [ Time Frame: Screening, pre-dose, 30 mins post dose, 4 hours post dose, 8 hours post dose and follow-up in each dosing session ] [ Designated as safety issue: Yes ]
- Safety laboratory assessments for all study participants [ Time Frame: Part A: Screening, pre-dose, 24 hours post dose and follow-up in each dosing session. Part B: Screening, pre-dose and 8 hours post dose on Day 1, 0 hours and 8 hours post dose on Day 2, follow-up ] [ Designated as safety issue: Yes ]To include haematology and clinical biochemistry assessments
- Cardiac troponin measurements for all study participants [ Time Frame: Part B only: Screening, pre-dose and 24 hours post dose on Day 1 ] [ Designated as safety issue: Yes ]
- Palatability by identification of solution taste and 11 point scale [ Time Frame: 30 minutes post dose ] [ Designated as safety issue: No ]
- Systemic pharmacokinetics of GSK2339345 using plasma concentrations of GSK2339345 and derived pharmacokinetic parameters [ Time Frame: Pre-dose to 24 hours post dose ] [ Designated as safety issue: Yes ]
- Effect of an inhaled nebulised dose of GSK2339345 on cough response to capsaicin challenge in healthy volunteers [ Time Frame: Part B: Day 2, 10 minutes post dose ] [ Designated as safety issue: No ]
|Study Start Date:||October 2011|
|Study Completion Date:||March 2012|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Experimental: GSK2339345 (solution) (part A)
Drug: GSK2339345 (solution)
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.
Experimental: GSK2339345/ Placebo/ Lidocaine (nebulised) (part B)
Drug: GSK2339345 (nebulised)
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.Drug: Placebo (0.9% sodium chloride solution)
Administered on Day 1 of one of the treatment periods in part B. Randomised. Nebulised.Drug: Lidocaine
40mg dose. Administered on Day 2 of one of the treatment periods in part B. Randomised. Nebulised.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01494636
|GSK Investigational Site|
|Manchester, United Kingdom, M23 9QZ|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|