Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single, Oral Escalating Doses of GSK2647544 in Healthy Volunteers

The current study will examine the safety, tolerability, plasma pharmacokinetics (PK), and plasma pharmacodynamics (PD) of single-doses of GSK2647544.The study will be conducted as a randomized, single-blind, placebo controlled, 4-way crossover single oral ascending dose design in 2 independent cohorts, eight healthy male subjects in each of the cohorts. Each potential subject will undergo Screening visit, Treatment Phase and Follow-up visit.


Eligibility Criteria:
Inclusion Criteria:

* Healthy males who are 18 to 55 years of age, inclusive
* Healthy as determined by a responsible and experienced physician
* aspartate aminotransferase (AST), Alanine transaminase (ALT), alkaline phosphatase and bilirubin \<= 1.5xUpper Limit of Normal (ULN)
* Average of triplicate QTcB values and average of triplicate QTcF values must both \< 450 millisecond (msec)
* Body weight \> 50 kg (110 pounds) and body mass index (BMI) between 19 and 30
* Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods
* Capable of giving written informed consent

Exclusion Criteria:

* Those with Lp-PLA2 activity \<=20 nanomole/minute/milliliter (mL)(for subjects with 2 known birth parents of at least 50% Japanese, Chinese, or Korean ancestry)
* History of asthma, anaphylaxis or anaphalactoid reactions, severe allergic responses
* History of hypercoagulable state or history of thrombosis
* A history of biliary tract disease including a history of liver disease with elevated liver function tests of known or unknown etiology
* Positive Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C at screening
* History of regular use of tobacco- or nicotine-containing products within three months of the study and/or has a positive breath CO at screening
* History of alcohol consumption exceeding, on average, 21 drinks/week for men (1 drink = 100 mL of wine or 240 mL of beer or 30 mL of hard liquor in Australia) within 6 months of the first dose of study medication
* Positive urine drug or positive breath alcohol test at screening or at admission to Clinical Research Unit
* Unable to refrain from use of prescription or non-prescription drugs and vitamins within 7 days or 5 half-lives (whichever is longer) prior to administration of study
* Unable to refrain from use of dietary/herbal supplements including (but not limited to) St. John's wort, kava, ephedra (ma huang), gingko biloba, DHEA, yohimbe, saw palmetto, ginseng and red yeast rice within 14 days prior to treatment with study medication
* Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing
* Unable to refrain from consumption of grapefruit or grapefruit juice within 7 days prior to the first dose of study medication
* For male subjects, an unwillingness to abstain from sexual intercourse with pregnant or lactating women or an unwillingness to use a condom plus partner use of a highly effective contraceptive if engaging in sexual intercourse with a woman who could become pregnant until discharge from the study
* Donation of blood in excess of 500 mL within 56 days prior to dosing
* History of sensitivity to heparin or heparin-induced thrombocytopenia
* Subjects, who in the investigator's judgement, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behaviour and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 6 months