GSK1278863 Effects on Eccentric Exercise-Induced Muscle Damage

Inclusion Criteria:

- A subject will be eligible for inclusion in this study only if all of the following
criteria apply:

- Males between 18 and 35 years of age inclusive, at the time of signing the informed
consent.

- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and
cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s)
which is/are not specifically listed in the inclusion or exclusion criteria, outside
the reference range for the population being studied may be included only if the
Investigator in consultation with the GSK Medical Monitor agree and document that the
finding is unlikely to introduce additional risk factors and will not interfere with
the study procedures. Subjects with hemoglobin values outside the normal range should
always be excluded from enrolment.

- Body weight >= 70 kilogram (kg) and Body mass index (BMI) within the range 22.0 to
34.0 (inclusive).

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- 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%).

- Corrected QT interval (QTc) < 450 milliseconds (msec) based on single or average QTc
value of triplicate values obtained over a brief recording period. The QT correction
formula (Fridericia's) used to determine inclusion and discontinuation should be the
same throughout the study.

- At least a 1year history of no regular (2-3 times per week) exercise and no heavy
exertion within past week, and in the examining physician's opinion the study
participant's physical condition/physique is consistent with a history of no regular
physical activity for the past year.

- No strenuous exercise involving the arms during the last 10 weeks (e.g., resistance
training, rock climbing, rowing, chopping wood, digging, shovelling, sawing).

- The subject is mentally and legally able to comply with the requirements and
restrictions of the protocol and has provided signed informed consent prior to
participation in any protocol-specific procedures, including Screening procedures.

Exclusion Criteria:

- A subject will not be eligible for inclusion in this study if any of the following
criteria apply:

Criteria Based Upon Medical History

- History of dizziness or vertigo.

- Uncontrolled hypertension [diastolic blood pressure (BP) >100 millimeter of mercury
(mmHg) or systolic BP >170mmHg] at Screening.

- Taking anti-inflammatory, glucocorticoid or other pain medication more than 2 times
per week over the previous month.

- Unwilling to abstain from taking prescription or non-prescription drugs (including
vitamins and dietary or herbal supplements), 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 until completion of the follow-up visit, unless in the
opinion of the Investigator and sponsor the medication will not interfere with the
study.

- History of regular alcohol consumption within 6 months of the study defined as:

An average weekly intake of >14 drinks for males. One drink is equivalent to 12 grams(g)
of alcohol: 12 ounces [360 milliliter (mL)] of beer, 5 ounces (150mL) of wine or 1.5
ounces (45mL) of 80 proof distilled spirits.

- History of drug abuse or dependence within 6 months of the study.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- 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 peptic ulcer disease or upper gastrointestinal (GI) bleeding within the
past 6 months.

- History of thrombosis defined as deep vein thrombosis, stroke, pulmonary embolism or
other thrombosis related condition within 3 months prior to Screening.

- History of myocardial infarction or acute coronary syndrome within 3 months prior to
Screening.

- History of stroke or transient ischemic attack within 3 months prior to Screening.

- Subjects with a pre-existing condition interfering with normal gastrointestinal
anatomy or motility, and/or hepatic function that could interfere with the
absorption, metabolism, and/or excretion of GSK1278863. Examples of conditions that
could interfere with normal gastrointestinal anatomy or motility include
gastrointestinal bypass surgery, partial or total gastrectomy, small bowel resection,
vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or celiac sprue.
Examples of conditions that could interfere with hepatic function include Gilbert's
syndrome.

- Evidence of active peptic, duodenal or esophageal ulcer disease at Screening OR
history of clinically significant GI bleeding within 3 months prior to Screening.

- Subjects with chronic inflammatory disease that could impact erythropoiesis (e.g.,
scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease).

- Subjects with a history of symptomatic right heart failure.

- Subjects with Class III or Class IV heart failure, as defined by the New York Heart
Association (NYHA) functional classification system.

- History of proliferative vascular eye disease (e.g., choroidal or retinal disease,
such as neovascular age-related macular degeneration, proliferative diabetic
retinopathy or macular edema) based upon having had an ophthalmologic exam within 12
months prior to Screening.

- History of risk factors for hypercoagulable state:

- Factor V Leiden (the most common)

- Prothrombin gene mutation

- Deficiencies of natural proteins that prevent clotting (such as antithrombin III,
protein C and protein S)

- Recent vascular trauma or surgeryd

- Central venous catheter placement

- Obesity

- Antiphospholipid antibody syndrome

- Myeloproliferative disorders such as polycythemia vera or essential thrombocytosis

- Paroxysmal nocturnal hemoglobinuria

- Nephrotic syndrome

- Active malignancy or diagnosis of malignancy within 5 years prior to Screening
(excluding successfully treated basal or squamous cell carcinoma).

Criteria Based Upon Diagnostic Assessments

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.

- Urinary cotinine levels indicative of 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 minimum list of drugs that will be
screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and
benzodiazepines.

- A positive test for HIV antibody.

- Screening hemoglobin level > 17.0 grams per deciliter (g/dl).

- Screening Creatine phosphokinase (CPK) > 5xULN.

- Screening serum creatinine >1.10. Other Criteria

- Where participation in the study would result in donation of blood or blood products
in excess of 500mL within a 56-day period.

- 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.

- Unwillingness or inability to follow the procedures, or lifestyle and/or dietary
restrictions outlined in the informed consent and as directed by site staff.

- Subject is either an immediate family member of a participating Investigator, study
coordinator, employee of an Investigator; or is a member of the staff conducting the
study.