Single Dose Escalation First Time in Human PK Study

Inclusion criteria

• Healthy
• male
• non-childbearling potential females
• Body weight greater than or equal to 50 kg (110 lbs) for men and greater than or equal to 45 kg (99 lbs) for women. Body mass index (BMI) between 18.5-29.9 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; or QTc < 480 msec in subjects with Bundle Branch Block on Screening ECG

Exclusion criteria

• The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A positive test for HIV antibody.
• History of regular alcohol consumption within 6 months of the study defined as:

an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). A standard unit is defined as 10g ethanol which is equivalent to 100mL wine, 250mL full strength beer, 470mL light beer, 30mL spirits

• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the 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 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, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• 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.
• Pregnant females as determined by positive [serum or urine] human chorionic gonadotropin (hCG) test at screening or prior to dosing.
• Lactating females.
• Subjects who have asthma or a history of asthma within the past 6 months.
• History of smoking or history of regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pummelos, satsuma, ugli, tangerine, and tangelo, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication