Assessment of the Pharmacokinetics of GSK1278863 and Metabolites in Normal Subjects and Subjects With Renal Impairment

Inclusion Criteria:

All Study Participants

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

- Adults between 18 and 75 years of age at the time of Screening.

- A female subject is eligible to participate if she is of childbearing potential, and
must agree to use one of the contraception methods described in the protocol. This
criterion must be followed from the time of Screening until completion of the
Follow-up Visit. OR Non-childbearing potential as defined in the protocol.

- Male subjects with female partners of child-bearing potential must agree to use one of
the contraception methods in the protocol. This criterion must be followed from the
time of the first dose of investigational product until completion of the Follow-up
visit.

- Satisfactory medical evaluation based upon medical history, medication history,
physical examination, and clinical laboratory data obtained at the screening visit.

- Body weight ≥ 45 kg and ≤ 140 kg at screening. For Stage 5 subjects, body weight is
dry weight after hemodialysis.

- QTcF < 450 msec; OR QTcF < 480 msec in subjects with Bundle Branch Block. These should
be based on average of triplicate values obtained over brief recording period at
screening and Predose on Day 1.

- Vitamin B12 and folate above the lower limit of normal at screening.

- 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.

Additional Inclusion Criteria for Subjects with Normal Renal Function

- Has normal creatinine clearance (CLCR) via the Cockcroft-Gault equation, using serum
creatinine and demographic data, obtained at Screening. Normal subjects should have no
greater than trace blood or protein on Screening urinalysis.

- A hemoglobin value at screening is greater than the lower limit of the reference range
for the local laboratory and less than or equal to 16.0g/dL

- No greater than trace blood on screening urinalysis

- Laboratory values for which specific criteria are not defined within the inclusion and
exclusion criteria for this study must be within the normal range or deemed not
clinically significant. A normal subject with a clinical abnormality or laboratory
parameters outside the reference range 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, or the integrity of the
study.

Additional Inclusion Criteria for Subjects with Renal Impairment

- Has Stage 3 or Stage 4 renal function (not receiving dialysis) as determined by
estimated Glomerular Filtration Rate (eGFR) calculated by the abbreviated MDRD
equation OR has Stage 5 renal function (end-stage renal failure) and has been on
stable hemodialysis treatment scheduled three times weekly for 3 months prior to
screening and the serum creatinine value at the Day -1 visit must be within +/- 20% of
the screening value.

- Is otherwise considered clinically stable with respect to underlying renal impairment
as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and ECG.

- has clinical laboratory test results that are considered clinically stable in the
opinion of the Investigator, especially if the clinical abnormality or laboratory
parameter is deemed associated with the subject's underlying renal impairment.

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

- Meets the following erythropoiesis stimulating agent (ESA) criteria: The subject is
ESA naïve OR the subject has a scheduled ESA interval which is ≤ 7 days, ESA treatment
must be discontinued for at least 7 days OR the subject has a scheduled ESA interval
which is > 7 days, ESA treatment must be discontinued for at least that scheduled
interval length (e.g. discontinued ≥ 14 days for a scheduled 14 day ESA interval) AND
the subject will not resume ESA treatment until completion of the Follow-up Visit.

- Has a hemoglobin value: For ESA naïve subjects: ≤11.0 g/dL or subjects receiving
ongoing ESA treatment: ≤12.0 g/dL at screening with a re check value of ≤11.0 g/dL
after appropriate ESA discontinuation according to the Inclusion criterion on use of
ESAs and prior to commencing investigational product dosing.

Exclusion Criteria:

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

All Study Participants

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result at Screening.

- A positive test for HIV antibody.

- Uncontrolled hypertension (diastolic BP >100 mmHg or systolic BP >160 mmHg at
Screening.

- A positive drugs of abuse and alcohol screen.

- History of regular alcohol consumption within 6 months of the study as described in
the protocol.

- History of regular use of tobacco- or nicotine-containing products within 6 months of
the study in excess of 20 cigarettes per day or equivalent.

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

- History of sensitivity to any of the investigational products, 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.

- The subject has participated in a clinical trial and has received an experimental
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).

- History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical
research unit uses heparin to maintain intravenous cannula patency).

- History of thrombosis defined as deep vein thrombosis, stroke, pulmonary embolism or
other thrombosis related condition within 1 year prior to Screening.

- History of myocardial infarction or acute coronary syndrome within 1 year 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 the investigational product. 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 Gilbert's syndrome.

- Evidence of active peptic, duodenal or esophageal ulcer disease at Screening.

- History of chronic rectal bleeding.

- Subjects with polycystic kidney disease.

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

- Subjects with chronic lung disease requiring supplemental oxygen.

- Patients with a diagnosis of pulmonary artery hypertension.

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

- Post-renal transplantation subjects with functioning transplant. Note: Failed
transplant subjects back on hemodialysis are eligible for participating in this study
but should not be on immunosuppressive medications for past 3 months at Screening.

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

- History of proliferative vascular eye disease (e.g., choroidal or retinal disease,
such as neovascular age-related macular degeneration or proliferative diabetic
retinopathy or wet macular edema) based on verbal confirmation having had an
ophthalmologic exam within 12 months of screening.

- Pregnant females as determined by positive serum beta-hCG test at Screening and Day
-1.

- 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 informed consent and as directed by site staff.

- Consumption 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.

- 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.

Additional Exclusion Criteria for Subjects with Normal Renal Function

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

- The values of the following tests at screening are: - TIBC: outside the reference
range and serum iron: outside the reference range and serum ferritin: outside the
reference range.

- Use or planned use of any prescription or non-prescription drugs that are prohibited
as defined in the protocol 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
investigational product until completion of the follow-up visit unless in the opinion
of the investigator or GSK Medical Monitor the medication will not interfere with the
study procedures or compromise subject safety.

Additional Exclusion Criteria for Subjects with Renal Impairment

- The values of ferritin and transferrin at Screening for renal impaired subjects are:
transferrin saturation ≥ 20% and serum ferritin < 100 μg/L

- Taking a prohibited medication or supplement (with the exception of approved vitamins
or minerals 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 investigational product
until completion of the follow-up visit, unless in the opinion of the Investigator and
sponsor the medication will not interfere with the study. The following medications
are specifically prohibited from screening to the follow-up visit: non-steroidal
anti-inflammatory drugs (NSAID) and immunosuppressant drugs and drugs used to treat
malignancies.