Study to Assess the Pharmacokinetics of GSK1278863A Coadministered With a High Fat Meal or an Inhibitor of CYP2C8 (Gemfibrozil)
Study to Assess the Pharmacokinetics of GSK1278863A Coadministered With a High Fat Meal or an Inhibitor of CYP2C8 (Gemfibrozil)
Study to Assess the Pharmacokinetics of GSK1278863A Coadministered with a High Fat Meal or an
 Inhibitor of CYP2C8 (gemfibrozil),]
The purpose of this study is to assess the clinical drug-drug interaction potential of
 GSK1278863A with medications that are inhibitors of CYP2C8 enzyme in order to support
 co-administration of similar agents in later phase development. Specifically. this study will
 assess the pharmacokinetics of a single dose of GSK1278863A administered alone or
 co-administered with gemfibrozil, a potent inhibitor of CYP2C8, following steady-state oral
 administration of gemfibrozil. Finally, to support the co-administration of GSK1278863A with
 food, this study will assess the pharmacokinetics of a single oral dose of GSK1278863A under
 fasting conditions and following a standard high-calorie, high fat meal.
Inclusion Criteria:

 -  AST, ALT, alkaline phosphatase and bilirubin > 1.5xULN (isolated bilirubin >1.5xULN is
 acceptable if bilirubin is fractionated and direct bilirubin <35%)

 -  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 parameters
 outside the reference range for the population being studied may be included only if
 the Investigator and the GSK Medical Monitor agree that the finding is unlikely to
 introduce additional risk factors and will not interfere with the study procedures

 -  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 or hysterectomy; or
 postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a
 blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and
 estradiol < 40 pg/ml (<140 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 in Section 8.1 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 must agree to use one of the contraception methods listed in Section
 8.1. This criterion must be followed from the time of the first dose of study
 medication until 5 terminal half-lives post-last dose

 -  Body weight < 50 kg and BMI within the range 19 - 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 or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block

 Exclusion Criteria:

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

 -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
 (with the exception of Gilbert's syndrome or asymptomatic gallstones)

 -  The values of hematological parameters at screening are: Any values outside the
 reference range

 -  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

 -  The values of the following tests at screening are: Serum ferritin: outside the
 reference range

 -  A positive test for HIV antibody

 -  Clinically significant CPK >3 X ULN or deemed clinically significant by the
 investigator

 -  Calculated creatinine clearance: < 80 mL/min

 -  Subjects with a pre-exisisting condition interfering with normal gastrointestinal
 anatomy or motility, and/or hepatic function-that could interfere with the absorption,
 metabolism, and/or excretion of the study drugs. Examples of conditions that could
 interfere with normal gastriointestinal anatomy or motility include cholecystectomy,
 vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or celiac sprue

 -  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 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine
 or 1 (25 ml) measure of spirits

 -  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: 12 weeks, 5 half-lives or twice the duration of the biological effect of the
 investigational product (whichever is longer)

 -  History of peptic ulcer disease

 -  History of malignancy tumor. Non-melanoma skin cancer that has been definitely removed
 is allowed

 -  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 (including St John's Wort) within 14 days 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 hCG test at screening or
 prior to dosing

 -  Lactating females

 -  Unwillingness or inability to follow the procedures outlined in the protocol

 -  Subject is mentally or legally incapacitated

 -  History of sensitivity to heparin or heparin-induced thrombocytopenia

 -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
 nicotine-containing products within 6 months prior to screening

 -  Consumption of red wine, apples, star fruit, or citrus fruits/juices including blood
 oranges (with the exception of oranges, mandarins and lemons) from 7 days prior to the
 first dose of study medication, unless in the opinion of the Investigator and GSK
 Medical Monitor this will not interfere with the study procedures and compromise
 subject safety