A Study to Evaluate the Effect of Two Different Repeat Doses of GSK2190915 on the QTc Interval.

This study is a randomized, placebo controlled, four way crossover, in which the the effect of GSK2190915 on the QTc interval is assessed. Healthy subjects will recieve a 5 day course of each of the following; oral placebo, GSK2190915 100mg, GSK2190915 1000mg and moxifloxacin 400mg (single dose) with a weeks washout prior to starting the next course. Key assessments include a 12- lead electrocardiogram and pharmacokinetic testing. Safety will be assessed by blood pressure, heart rate, clinical laboratory safety tests and collection of adverse events .

This is a randomized, placebo controlled, four way crossover thorough QT study to evaluate the effect of repeat dose GSK2190915 on the QTc interval in healthy male and female subjects. Approximately 48 subjects will receive oral placebo, GSK2190915 (100mg or 1000mg) and moxifloxacin (400mg). GSK2190915 or matching placebo will be given once daily for 5 days with a moxifloxacin matching placebo given on Day 5. Moxifloxacin (positive control) will be given as a single-blind single dose on Day 5 with placebo administered on Days 1-4. Individual time-matched changes from baseline in QTcF (difference from placebo) for GSK2190915 will be determined 0-24 hours after dosing on Day 5 (primary endpoint). Secondary endpoints will include changes from baseline in QTcF, QTcB and QT interval at each timepoint after 5 days dosing of GSK2190915 and single dose moxifloxacin (400mg). Plasma concentrations on Day 5 (0-24 hours) and pharmacokinetic parameters of GSK2190915 will also be derived.

Eligibility Criteria:
Inclusion Criteria:

* Male or female between 18 and 65 years of age inclusive
* Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper limit of normal (ULN)
* Healthy as determined by a physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
* A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal . Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods. Those of child-bearing potential must agree to use one of the protocol contraception methods.
* Body mass index (BMI) within the range 18.5-29.0 kg/m2 (inclusive)
* Capable of giving written informed consent
* Current non-smokers who have not used tobacco products in the 6 month period preceding screening
* No significant abnormality on 12-lead electrocardiogram (ECG) at screening
* A 24 hour Holter ECG at screening that demonstrates no clinically significant abnormalities

Exclusion Criteria:

* A physician deems the subject unsuitable for the study
* A screening Holter ECG tracing that reveals clinically concerning arrhythmias
* A blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg) at screening.
* A mean heart rate outside the range 40-90 beats per minute (bpm) at screening.
* History or presence of any medically significant disease, or any disorder. In particular, a family history of QT prolongation, of early or sudden cardiac death or of early cardiovascular disease.
* A positive result for Hepatitis B or Hepatitis C within 3 months of screening
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities
* A positive pre-study drug/alcohol screen
* A positive test for Human Immunodeficiency Virus (HIV) antibody
* 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 3 months of the first dosing day in the current 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 from 14 days before screening until the follow-up visit unless permitted by the investigator
* History of sensitivity to any of the study medications
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 3 month period
* Pregnant females
* Lactating females
* Unwillingness or inability to follow the procedures outlined in the protocol
* Subject is mentally or legally incapacitated