Effect of GSK1014802 on Electrical Hyperalgesia and Threshold Tracking in Healthy Subjects

Inclusion Criteria:

• Male between 18 and 55 years of age inclusive.
• AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN
• Healthy as determined by a responsible and experienced physician.
• Male subjects must agree to use one of the contraception methods requested.
• Body weight greater than or equal to 50 kg, BMI ≤29.9kg/m2
• Capable of giving written informed consent.
• QTcB or QTcF < 450 msec.

Exclusion Criteria:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result.
• 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.
• A positive test for HIV antibody.
• Heart block, bundle branch block, hemi-block, evidence of accessory cardiac conduction pathways, long pauses >2 s or other cardiac conduction abnormalities or cardiac arrhythmias on 12-lead ECG or 24 h Holter at screening.
• History of regular excessive alcohol consumption within 6 months of the study.
• The subject has participated in a clinical trial and has received an investigational product within 90 days o fthe strat of this study.
• 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.
• 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.
• Subjects with a 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.
• Average daily caffeine intake equivalent to > 4 cups of coffee or > 6 cups of tea.
• Current or past history of symptomatic orthostatic hypotension or history of vasovagal episode(s).
• Subjects with systolic blood pressure persistently above 140 mmHg and/or diastolic blood pressure persistently above 90 mmHg.
• History of known or suspected seizures, including infantile febrile, unexplained significant and recent loss of consciousness or history of significant head trauma with loss of consciousness or a family history (first degree relative) of epilepsy or seizures (fits).
• The subject has a history of chronic pain before screening.
• The subject has used any topical steroid in the previous 30 days if, in the opinion of the investigator this is likely to interfere with study assessments.
• The subject has used any topical capsaicin preparations on the forearms in the previous 30 days.
• The subject suffers from eczema, psoriasis or any other acute or chronic dermatological problem if, in the opinion of the investigator this is likely to interfere with study assessments
• The subject suffers from tinnitus, or has done in the past 3 months.
• Suffers from skin infection or inflammation of the forearm, or has other arm skin irregularities that may in the opinion of the investigator interfere with study assessments.
• Needle phobic.
• The subject does not produce an area of allodynia or hyperalgesia to the electrical hyperalgesia model during the screening session.
• The subject is unable to tolerate the electrical hyperalgesia model or threshold tracking, including anxiety or atypical response to the stimulation.
• Any history of suicidal behaviour or any suicidal ideation of type 4 or 5 on the C-SSRS in the last month.
• Poor veins that would be estimated not to be suitable by a physician for repeated cannulation in both arms.