Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1278863A in Healthy Subjects
Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1278863A in Healthy Subjects
GSK1278863A is a novel small molecule agent, which stimulates erythropoiesis through
 inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylases (EGLNs). This compound is
 being developed for the treatment of anemia. This study, PHI115385, will be the first
 administration of GSK1278863A to Japanese subjects to investigate the safety, tolerability,
 pharmacokinetics, and pharmacodynamics of single oral doses in healthy Japanese adult
 subjects. Healthy Caucasian adult subjects will be included in order to compare
 pharmacokinetics of GSK1278863A and its metabolite(s), and pharmacodynamics of GSK1278863A.
Inclusion Criteria:

 -  AST, ALT, alkaline phosphatase and bilirubin >1.5xULN.

 -  Healthy Male or female between 20 and 65 years of age inclusive, at the time of
 signing the informed consent.

 -  Male subjects with female partners of child-bearing potential must agree to use one of
 the contraception methods.

 -  Body weight > 50 kg and BMI within the range 18.5 - 29.0 kg/m2 (inclusive).

 -  Capable of giving written informed consent.

 -  QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

 -  Japanese defined being born in Japan, having four ethnic Japanese grandparents,
 holding a Japanese passport or identity papers and being able to speak Japanese.
 Japanese subjects should be also have lived outside Japan for less than 10 years.

 -  Caucasian, defined as an individual having four grandparents who are all descendents
 of the original peoples of Europe.

 Exclusion Criteria:

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

 -  A positive pre-study drug screen. A minimum list of drugs that will be screened for
 include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines

 -  A hemoglobin value at Screening is of: Healthy male subjects or post-menopausal
 females: > 16.5 g/dL, Healthy female (non-childbearing potential) subjects: > 15.5
 g/dL

 -  The values of hematological parameters at screening are: MCV: outside the reference
 range and deemed clinically significant by the investigator and GSK Medical Monitor.

 -  The values of the following tests at Screening, for healthy subjects are: TIBC:
 outside the reference range of the population being studied, Serum iron: outside the
 reference range of the population being studied, Serum ferritin: outside the reference
 range of the population being studied

 -  A value at screening is greater than the upper limit of reference range for the
 following clinical laboratory parameters: AST, ALT, direct bilirubin.

 -  Clinically significant abnormal CPK determined by the Investigator and GSK Medical
 Monitor.

 -  Calculated creatinine clearance: < 80 mL/min

 -  A positive test for HIV antibody

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

 -  History of regular alcohol consumption within 6 months of the study

 -  History or regular use of tobacco- or nicotine-containing products within 6 months
 prior to screening.

 -  Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
 supplements (including St John's Wort) 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, unless in the opinion of the Investigator and GSK Medical
 Monitor the medication will not interfere with the study procedures or compromise
 subject safety. By exception, subject may take acetaminophen (<2 grams/day) up to 48
 hours prior to the first dose of study drug.

 -  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 (if the clinical
 research unit uses heparin to maintain intravenous cannula).

 -  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 the study drugs. Examples of conditions that could
 interfere with normal gastrointestinal anatomy or motility include cholecystectomy,
 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 Gilberts
 syndrome.

 -  History of peptic ulcer disease or chronic rectal bleeding.

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

 -  Subjects with a baseline medical history of proliferative diabetic retinopathy,
 preproliferative diabetic retinopathy, or wet age-related macular degeneration (AMD).

 -  Pregnant females as determined by positive serum or urine hCG test at screening or
 prior to dosing.

 -  Lactating females.

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

 -  Unwillingness or inability to follow the procedures, or lifestyle and/or dietary
 restrictions outlined in the protocol.

 -  Consumption of >3 servings per day of red wine, grapefruit (juice), blood orange
 (juice), star fruit, onions, kale, broccoli, green beans, or apples from 7 days prior
 to the first dose of investigational product, unless in the opinion of the
 Investigator and GSK Medical Monitor this will not interfere with the study procedures
 and compromise subject safety.

 -  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.

 -  Subject is mentally or legally incapacitated.