4 Week Correction Study in Subjects With Anemia Associated With Chronic Kidney Disease Who Are Not Undergoing Dialysis

This is a four-week Phase IIa, randomized, double-blind, placebo-controlled, parallel-group,
multi-center study to evaluate the safety, efficacy and pharmacokinetics of GSK1278863 in
approximately 68 subjects with anemia associated with chronic kidney disease who are not
taking rhEPO and are not undergoing dialysis. The study consists of a screening phase of up
to 2 weeks, a 4-week treatment phase and a 2-week follow-up phase. The range of Hgb values
for study eligibility is 8.5-11.0 g/dL. Eligible subjects will be randomized in equal
proportions to receive once daily (QD) placebo or GSK1278863 0.5 mg, 2 mg or 5 mg in a
double-blind fashion. Study treatment will be stopped if Hgb values fall outside of the range
pre-specified in the protocol.

This study aims to estimate the relationship between dose of GSK1278863 and Hgb response for
correcting anemia in non-dialysis subjects with CKD who are not taking rhEPO (NDD). In
addition, the study will characterize the effect of GSK1278863 on various
pharmacokinetic/pharmacodynamic (PK/PD) markers, and will investigate the safety and
tolerability of GSK1278863.

An early interim analysis of the Hgb data is planned after approximately 20 subjects from
cohort 1 have completed 3 weeks of treatment. Depending upon the interim findings, a second
cohort of subjects may be added to investigate an additional GSK1278863 dose arm. Recruitment
to the first cohort will continue during the interim analysis.

A second interim analysis is planned after approximately 48 subjects from cohort 1 have
completed 4 weeks treatment. The purpose of this interim is three-fold, to investigate
whether a second cohort of subjects may be added, to facilitate early development of
dose-response and PK/PD statistical models, and to generate interim results to facilitate
design and dosing decisions for the next trial.

Subject completion is defined as completion of all study phases including the follow-up
phase.

Inclusion Criteria:

1. Age and weight: >/= 18 years of age and >/= 45 kg.

2. Not routinely undergoing dialysis, regardless of the modality (either hemodialysis or
peritoneal dialysis) or dialysis planned during the time the subject would be enrolled
in the study.

3. No current or prior rhEPO use within the past 7 weeks; e.g., epoetins (or their
biosimilars), darbepoetin, Mircera (methoxy polyethylene glycol epoetin beta),
peginesatide or their biosimilars..

4. KDOQI CKD stages 3/4/5 defined by eGFR using the Modification of Diet for Renal
Disease (MDRD).

5. Hgb: Hgb concentrations 8.5-11.0 g/dL (inclusive) as outlined in Section 4.2.

6. Vitamin B12: Above the lower limit of the reference range (may rescreen in 2 months).

7. Folate: >/=2.0 ng/mL at Screening. May rescreen in a month.

8. Ferritin: >/=40 ng/mL with the absence of microcytic or hypochromic RBCs.

9. TSAT within the reference range.

10. Iron replacement therapy: Stable maintenance dose of oral iron replacement therapy, if
required, that will be maintained throughout the study. NOTE: IV iron replacement
therapy is not allowed the two weeks prior to Screening through the end of the study
(Week 6).

11. QTc: QTcB <470 msec or QTcB <480 msec in subjects with bundle branch block obtained at
Screening Visit, based on Central Reader's interpretation.

12. Females: Eligible to participate if she is of childbearing potential, and must agree
to use approved contraception methods from Screening until completion of the Follow-up
Visit OR of non-childbearing potential defined as pre-menopausal females with a
documented tubal ligation of hysterectomy; or postmenopausal defined as 12 months of
spontaneous amenorrhea [in questionable cases a blood sample with simultaneous
follicle stimulating hormone (FSH)>40 MIU/ml and estradiol <40 pg/ml is confirmatory].
Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will
be required to use one of the approved contraception methods 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 types of HRT, at least 2
weeks will 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.

13. Males: Must agree to use approved contraceptive methods from the time of Screening
until completion of the Follow-up Visit.

Exclusion Criteria:

1. Dialysis: Planning to initiate dialysis during the study or who have a high potential
for initiating dialysis during study participation.

2. Renal transplant: Renal transplant anticipated or scheduled within the study time
period or subjects with a functioning renal transplant.

3. Total CPK: >5x the upper limit of the reference range.

4. HIV: Positive HIV antibody.

5. History of myocardial infarction or acute coronary syndrome within the prior 6 months.

6. History of stroke or TIAs.

7. Heart failure: Class III/IV heart failure, as defined by the New York Heart
Association (NYHA) functional classification system.

8. Hypertension: Poorly controlled hypertension, whether due to inadequate treatment, or
lack of treatment, defined as DBP >100 mmHg or SBP>160 mmHg.

9. Thrombotic disease: History of thrombotic disease (e.g., venous thrombosis such as
deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset
or worsening limb ischemia requiring intervention), or other thrombosis related
condition) within the prior 6 months.

10. Pulmonary hypertension: Known pulmonary hypertension and those at higher risk (than
normally associated with CKD) for pre-existing elevation in pulmonary pressure (e.g.,
significant heart failure or lung disease requiring supplemental oxygen, or those with
connective tissue diseases).

11. Inflammatory disease: Chronic inflammatory disease that could impact erythropoiesis
(e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac
disease).

12. Hematological disease: Any hematological disease including those affecting platelets,
the coagulation disorders (e.g., Protein C or S deficiency) or red blood cells (e.g.
sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma,
hemolytic anemia) or any other cause of anemia other than renal disease.

13. Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the
exception of Gilbert's syndrome or asymptomatic gallstones) or evidence at Screening
of abnormal liver function tests [alkaline phosphatase, ALT or AST > 2.0 x upper limit
of normal (ULN) or total bilirubin > 1.5 x ULN]; or other hepatic abnormalities that
in the opinion of the investigator would preclude the subject from participation in
the study.

14. Major surgery: Within the prior 12 weeks or planned during the study.

15. Transfusion: Blood transfusion within the prior 12 weeks or an anticipated need for
blood transfusion during the study.

16. Ulcer and Active GI Bleeding: Evidence of active peptic, duodenal, or esophageal ulcer
disease or active GI bleeding within the prior 12 weeks.

17. Acute infection: Clinical evidence of acute infection or history of infection
requiring intravenous (IV) antibiotic therapy the eight weeks prior to Screening
through Day 1 (randomization).

18. Malignancy: History of malignancy within 5 years of Screening or are receiving
treatment for cancer or those with a strong family history of cancer (e.g., familial
cancer disorders), with the exception of squamous cell or basal cell carcinoma of the
skin that has been definitively treated.

19. Hyperparathyroidism: Clinically significant hyperparathyroidism in the opinion of the
Investigator, including subjects with parathyroid hormone (PTH) values ≥600 pg/mL.

20. Eyes: History of proliferative retinopathy requiring treatment within the prior 12
months, or macular edema requiring treatment.

21. Severe reactions: History of severe allergic or anaphylactic reactions or
hypersensitivity to excipients in the investigational product.

22. Drugs and supplements: Use of any prescription or non-prescription drugs or dietary
supplements that are prohibited from Screening until the Follow-up Visit.

23. Androgens: New androgen therapy or changes to pre-existing androgen regimen within
prior 12 weeks.

24. Prior investigational product exposure: The subject has participated in a clinical
trial and has received an experimental investigational product within prior 30 days.

25. Protocol compliance: Unwillingness or inability to follow the procedures, or lifestyle
and/or dietary restrictions outlined in the protocol.

26. Other conditions: Any condition which in the investigators opinion should exclude the
subject from participating in the study.

27. Pregnancy and lactation: Pregnant females as determined by positive urine hCG test, OR
women who are lactating at Screening or during the trial.