The Safety, Tolerability, PK and PD of GSK2339345 in Healthy Subjects

Inclusion Criteria: * Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper Limit of Normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. * Male between 18 and 65 years of age inclusive, at the time of signing the informed consent. * Male subjects with female partners of child-bearing potential must agree to use an approved method of contraception, (double-barrier method or complete sexual inactivity by abstinence). This criterion must be followed from the time of the first dose of study medication until the follow up visit. * Non-smoker for at least 6 months with a pack history ≤ 5pack years (Pack years = (No. of cigarettes smoked/day/20) x No. of years smoked). * Body weight ≥ 50 kg and BMI within the range 19 - 32.0 kg/m2 (inclusive). * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * QTcB\< 450 msec * A 24 hour Holter ECG at screening that demonstrates no clinically significant abnormalities or finding that could interfere with interpretation of the study results, when assessed by an appropriately trained and experienced reviewer. Exclusion Criteria: * Hepatitis B or Hepatitis C positive * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * A positive pre-study drug/alcohol screen. * HIV positive * History of regular alcohol consumption within 6 months of the study * The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Exposure to more than four new chemical entities within 12 months prior to the first dosing day. * Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication. * Forced Expiratory Volume in one second (FEV1) less than 80% of the predicted value prior to dosing (Part B only) * Part B only: any subject who does not reach C5 following an oral inhalation challenge of capsaicin at a dose level of 250 μM at screening or Day -1, reaches C5 following an oral inhalation of placebo solution or has known hypersensitivity to capsaicin * Part A only: any subject who is unable to gargle with placebo solution * Any subject who is unable to perceive oropharyngeal numbness caused by lidocaine * Any subject who, upon oropharyngeal examination, is deemed by the Investigator to be unsuitable for oropharyngeal sensation assessments. This includes any injuries to the mucosa of the mouth or pharynx that could potentially increase systemic absorption e.g candidiasis. * Any patient with a history of swallowing difficulties. * Any subject who has a history of an allergic reaction to a local anaesthetic. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. * Unwillingness or inability to follow the procedures outlined in the protocol. * Subject is mentally or legally incapacitated. * Breath CO levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. * Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.