A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD) and Food Effect of Single or Repeat Doses of GSK2793660 in Healthy Subjects

This study is the first administration of GSK2793660 to humans and will evaluate the safety, tolerability, PK and PD of single oral ascending doses of GSK2793660, and of repeat oral doses of GSK2793660 in healthy subjects. The study will comprise two parts (Part A and Part B). Part A will consist of two cohorts of subjects, each taking part in a three-way cross over study, with ascending doses of GSK2793660 and placebo. Available safety, PK and PD data will be reviewed before each dose escalation. This will be followed by a food-effect arm in the cohort that received what is deemed to be the target clinical dose. Part B is planned to consist of up to two cohorts of subjects, each taking part in one 14 day repeat dose study period. Subjects will be dosed on Day 1 and then on Days 3-15. It is planned that two doses will be evaluated. The dose(s) to be tested will be selected based on safety, PK, and PD from Part A. The study is intended to provide sufficient confidence in the safety profile of the molecule and information on target engagement to allow progression to further studies.


Eligibility Criteria:
Inclusion Criteria:

* Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, and laboratory tests. A subject with a clinical abnormality or laboratory parameters outside the reference range, and which is not a part of an eligibility criterion, for the population being studied may be included only if the Investigator and GSK medical monitor consider the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures and outcome.
* Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
* A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, removal of both ovaries or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>21.7 International units per liter (IU/L) and oestradiol \<110 picomole per liter (pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods listed in the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks should elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
* Male subjects with female partners of child-bearing potential must agree to use one of the approved contraception methods as detailed in the protocol. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
* Body weight \>=50 Kilogram (kg) and Body Mass Index (BMI) within the range 19.9-30.0 kg/meter square (m\^2) (inclusive).
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* Based on averaged QT duration corrected for heart rate by Fridericia's formula (QTcF) values of triplicate ECGs obtained over a brief recording period: Average QTcF \<450 milliseconds (msec)
* Systolic blood pressure \<=130 millimeters of mercury (mmHg) and diastolic blood pressure 80 mmHg based on average values of triplicate blood pressure readings obtained over a brief period.
* Alanine aminotransferase (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%).

Exclusion Criteria:

* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* ECG finding of second or third degree heart block.
* History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 milliliter \[mL\]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* 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.
* History of sensitivity to heparin or heparin-induced thrombocytopenia.
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
* Urinary cotinine or exhaled breath carbon monoxide (CO) levels indicative of current smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
* A positive pre-study drug/alcohol screen.
* A positive test for human immunodeficiency virus (HIV) antibody.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. Blood donation will not exceed 500 mL for the entire 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.