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

Anaemia Clinical Trial

Official title:

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 Subjects With Anemia Associated With Chronic Kidney Disease Who Are Not Taking Recombinant Human Erythropoietin and Are Not Undergoing Dialysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01587898
• Other study ID #: 116581
• Status: Completed
• Phase: Phase 2
• First received: April 19, 2012
• Last updated: October 9, 2017
• Start date: May 17, 2012
• Est. completion date: May 7, 2013

Study information

• Verified date: August 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: May 7, 2013
• Est. primary completion date: May 7, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anaemia
• Anemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• GSK1278863
Tablet

Other:
• Placebo
Tablet

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Sudbury	Ontario
Germany	GSK Investigational Site	Aschaffenburg	Bayern
Germany	GSK Investigational Site	Demmin	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Lehrte	Niedersachsen
United States	GSK Investigational Site	Arlington	Texas
United States	GSK Investigational Site	Asheville	North Carolina
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Azusa	California
United States	GSK Investigational Site	Bakersfield	California
United States	GSK Investigational Site	Bethlehem	Pennsylvania
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Chino	California
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Corsicana	Texas
United States	GSK Investigational Site	Daytona Beach	Florida
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Edgewater	Florida
United States	GSK Investigational Site	Erie	Pennsylvania
United States	GSK Investigational Site	Evanston	Illinois
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Greenville	Texas
United States	GSK Investigational Site	Gurnee	Illinois
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	North Hollywood	California
United States	GSK Investigational Site	Ocala	Florida
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orange	California
United States	GSK Investigational Site	Pembroke Pines	Florida
United States	GSK Investigational Site	Port Charlotte	Florida
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Dimas	California
United States	GSK Investigational Site	Savannah	Georgia
United States	GSK Investigational Site	Silverdale	Washington
United States	GSK Investigational Site	Temple	Texas
United States	GSK Investigational Site	Uniontown	Pennsylvania
United States	GSK Investigational Site	West Hills	California
United States	GSK Investigational Site	Wilmington	North Carolina
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Yuba City	California

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	PPD

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modeled Hgb Change From Baseline Over 4 Weeks of Treatment	Modeled Hgb change from baseline over 4 weeks was derived using a random coefficient mixed effects linear regression model. The model included fixed effects for baseline Hgb, treatment and a treatment by day interaction. Random effects was fitted in the intercept and the slope over time. All data up until investigational product discontinuation was included for Hgb efficacy evaluable participants; where efficacy evaluable was defined as having a baseline and at least 2 on-treatment Hgb assessments. Baseline was the average of Week -2 , Week -1 and Day 1 visits. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.	Baseline (average of Week -2, -1 and Day 1) and Week 4
Secondary	Model-Adjusted Maximum Hgb Changes Over 4 Weeks	Maximum Hgb change over 4 weeks was analyzed using an ANCOVA model with terms included for treatment and baseline Hgb value. Least square mean estimates and 95% CI for each treatment group were reported. Baseline was the average of Week -2 , Week -1 and Day 1 visits. The change from Baseline was calculated by subtracting the baseline value from the individual post-dose visit values.	Baseline (average of Week -2 , -1 and Day 1 visits) and 4 weeks
Secondary	Number of Participants Achieving an Increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb	Number of participants achieving an increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb from baseline were reported. Entry into the study required a target stable Hgb of 8.5-11.0 g/dL. A stable Hgb value was confirmed from three Hgb values taken during the screening period at Week -2, Week -1 and Day 1 (randomization). The average of these three values was used for Baseline Hgb.	Up to 4 weeks
Secondary	Percentage of Participants Achieving an Increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb	Percentage of participants achieving an increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb from baseline were reported. Entry into the study requires a target stable Hgb of 8.5-11.0 g/dL. A stable Hgb value was confirmed from three Hgb values taken during the screening period at Week -2, Week -1 and Day 1 (randomization). The average of these three values was used for Baseline Hgb.	Up to 4 weeks
Secondary	Number of Participants Who Reached Hgb Stopping Criteria	The Hgb stopping criteria was defined as reaching to value <8.0 g/dL, >=8.0 - <13.0 (>= 2g/dL absolute Hgb change over 1 week ) or >=13.0 g/dL. The number of participants who reached the Hgb stopping criteria of Hgb concentration were presented.	Up to Week 4
Secondary	Change From Baseline in Hepcidin at Week 2 and Week 4	Blood samples for hepcidin were collected at Day 1 (pre-dose), Week 2 (approximately between 4 to 8 h) and Week 4 (pre-dose). Hepcidin is a regulator of iron metabolism. Baseline was the last pre-dose value on Day 1. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. Where hepcidin values were missing because the value was below the quantification limit (BQL), the BQL value was imputed.	Baseline (Pre-dose on Day 1), Week 2 and 4
Secondary	Change From Baseline in Ferritin at Week 2 and Week 4	Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.	Baseline (Day 1 Pre-dose), Week 2 and 4
Secondary	Change From Baseline in Transferrin at Week 2 and Week 4	Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.	Baseline (Day 1 Pre-dose), Week 2 and 4
Secondary	Change From Baseline in Transferrin Saturation at Week 2 and Week 4	Transferrin saturation was measured as a percentage, and is the ratio of serum iron and total iron-binding capacity, multiplied by 100. Baseline value for transferrin saturation was the pre-dose value on Day 1. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.	Baseline (Day 1 Pre-dose), Week 2 and 4
Secondary	Change From Baseline in Total Iron Binding Capacity at Week 2 and Week 4	Total iron-binding capacity is a medical laboratory test that measures the blood's capacity to bind iron with transferrin. Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.	Baseline (Day 1 Pre-dose), Week 2 and 4
Secondary	Change From Baseline in Total Iron at Week 2 and Week 4	Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.	Baseline (Day 1 Pre-dose), Week 2 and 4
Secondary	Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) at Week 2 and Week 4	Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.	Baseline (Day 1 Pre-dose), Week 2 and 4
Secondary	Change From Baseline in Hematocrit and Reticulocytes Over 4 Weeks	Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.	Baseline (Day 1 pre-dose), Week 1, 2, 3, and 4
Secondary	Change From Baseline in Erythropoietin at Week 2 and Week 4	Blood samples for erythropoietin were collected at Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1 and 3 h after this fist sample) and Week 4 (Pre-dose and 3 h post-dose). The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.	Baseline (Day 1 Pre-dose), Week 2 and 4
Secondary	Change From Baseline in Red Blood Cells Count Over 4 Weeks	Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.	Baseline (Day 1 pre-dose), week 1, 2, 3, 4
Secondary	Change From Baseline in Vascular Endothelial Growth Factor (VEGF) at Week 2 and Week 4	Blood samples for VEGF were collected at Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1 and 3 h after this fist sample) and Week 4 (Pre-dose and 3 h post-dose). Baseline was the Day 1 pre-dose value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values.	Baseline (Pre-dose), week 2 and 4
Secondary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.	Up to 6 weeks
Secondary	Number of Participants Discontinuing the Study Treatment Due to AEs	AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. number of participants discontinuing the study treatment due to AEs.	Up to 6 weeks
Secondary	Absolute Values of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK) at Baseline (Day 1), Week 2, 4, and 6	Clinical chemistry parameters including ALT, ALP, AST, CK were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6).	Baseline (Day 1 pre-dose), Week 2, 4, and 6
Secondary	Absolute Values of Albumin, Apolipoprotein A1, Apolipoprotein Total, Total Protein at Baseline (Day 1), Week 2, 4, and 6	Clinical chemistry parameters including albumin, apolipoprotein A1, apolipoprotein total, total protein were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6).	Baseline (Day 1 pre-dose), Week 2, 4, and 6
Secondary	Absolute Values of Calcium, Chloride, Cholesterol, Glucose, Inorganic Phosphorus, Potassium, Sodium at Baseline (Day 1), Week 2, 4, and 6	Clinical chemistry parameters including calcium, chloride, cholesterol, glucose, inorganic phosphorus, potassium, sodium were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6).	Baseline (Day 1 pre-dose), Week 2, 4, and 6
Secondary	Absolute Values of Creatinine, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin at Baseline (Day 1), Week 2, 4, and 6	Clinical chemistry parameters including creatinine, direct bilirubin, indirect bilirubin, total bilirubin were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6).	Baseline (Day 1 pre-dose), Week 2, 4, and 6
Secondary	Absolute Values of Urine Total Protein/Creatinine Ratio at Baseline (Day 1), Week 2, 4, and 6	Absolute values of urine total protein/creatinine ratio at Baseline (Day 1), Week 2, 4, and follow-up (week 6) were reported.	Baseline (Day 1), Week 2, 4, and 6
Secondary	Change From Baseline Values of ALT, ALP, AST, CK at Week 2, 4, and 6	Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the Baseline value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. Change from Baseline values of ALT, AST, ALP and CK at Week 2, 4, and 6	Baseline (Day 1), Week 2, 4, and 6
Secondary	Change From Baseline Values of Albumin, Apolipoprotein A1, Apolipoprotein Total, Total Protein at Week 2, 4, and 6	Baseline values were recorded on Day 1 (Pre dose). If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of albumin, apolipoprotein A1, apolipoprotein total, total protein at Week 2, 4, and 6 were reported.	Baseline (Day 1), Week 2, 4, and 6
Secondary	Change From Baseline Values of Calcium, Chloride, Cholesterol, Glucose, Inorganic Phosphorus, Potassium, Sodium at Week 2, 4, and 6	Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of calcium, chloride, cholesterol, glucose, inorganic phosphorus, potassium, sodium at Week 2, 4, and 6 were reported.	Baseline (Day 1), Week 2, 4, and 6
Secondary	Change From Baseline Values of Creatinine, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin at Week 2, 4, and 6	Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of creatinine, direct bilirubin, indirect bilirubin, total bilirubin at Week 2, 4, and 6 were reported.	Baseline (Day 1), Week 2, 4, and 6
Secondary	Change From Baseline Values of Urine Total Protein/Creatinine Ratio at Week 2, 4, and 6	Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of urine total protein/creatinine ratio at Week 2, 4, and 6 were reported.	Baseline (Day 1), Week 2, 4, and 6
Secondary	Absolute Values of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count (Absolute) at Baseline, Week 1, 2, 3, 4, and 6	Hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet count, WBC count (absolute) were assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6).	Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Secondary	Absolute Values of Mean Corpuscle Volume at Baseline, Week 1, 2, 3, 4 and 6	Hematology parameter mean corpuscle volume was assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6).	Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Secondary	Absolute Values of Mean Corpuscle Hgb Concentration at Baseline (Day 1), Week 1, 2, 3, 4, and 6	Hematology parameter Mean Corpuscle Hgb Concentration was assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6).	Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Secondary	Absolute Values of Reticulocyte Count at Baseline (Day 1), Week 1, 2, 3, 4, and 6	Hematology parameter reticulocyte were assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6).	Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, WBC Count (Absolute) at Week 1, 2, 3, 4, and 6	Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet count, WBC count (absolute) at Week 1, 2, 3, 4, and 6 were reported.	Baseline (Day 1), Week 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Mean Corpuscle Volume at Week 1, 2, 3, 4, and 6	Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in Mean Corpuscle Volume at Week 1, 2, 3, 4, and 6 were reported.	Baseline (Day 1), Week 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Mean Corpuscle Hgb Concentration at Week 1, 2, 3, 4, and 6	Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in Mean Corpuscle Hgb Concentration at Week 1, 2, 3, 4, and 6 were reported.	Baseline (Day 1), Week 1, 2, 3, 4, and 6
Secondary	Absolute Values of Systolic Blood Pressure and Diastolic Blood Pressure Baseline, Week 1, Week 2, Week 3, Week 4 and Week 6	Absolute values of systolic blood pressure and diastolic blood pressure Baseline (Day 1), Week 1, 2, 3, 4, and 6 as vital parameters were reported. Three measurements of systolic blood pressure and diastolic blood pressure were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff).	Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Week 1, 2, 3, 4, and 6	Three measurements of SBP and DBP were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff). Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in systolic blood pressure and diastolic blood pressure at Week 1, 2, 3, 4, and 6 were reported.	Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Secondary	Absolute Values of Heart Rate at Baseline (Day 1), Week 1, 2, 3, 4, and 6	Absolute values of heart rate at Baseline (Day 1), Week 1, 2, 3, 4, and 6 were reported as vital parameter. Three measurements of heart rate were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff).	Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Heart Rate at Week 1, 2, 3, 4, and 6	Three measurements of heart rate were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff). Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. change from baseline in heart rate at Week 1, 2, 3, 4, and 6 were reported.	Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Secondary	Absolute Electrocardiogram (ECG) Parameter Values at Baseline (Screening), Week 2, 4, and 6	Full 12-lead ECGs were recorded in participants who were rested supine or seated for at least 10 minutes before each reading. All ECGs were transmitted to a central reviewer for blinded assessment. Full 12-lead ECGs were recorded on the provided ECG machine that automatically calculates heart rate, PR, QRS, QT and QTc intervals. Absolute ECG parameters including PR interval, QT interval and QRS duration values at Baseline (Screening), Week 2, 4, and 6 were reported.	Baseline (Screening), Week 2, 4, and 6
Secondary	Change From Baseline in ECG Parameters at Week 2, 4 and 6	Full 12-lead ECGs were recorded in participants who were rested supine or seated for at least 10 minutes before each reading. All ECGs were transmitted to a central reviewer for blinded assessment. Full 12-lead ECGs were recorded on the provided ECG machine that automatically calculates heart rate, PR, QRS, QT and QTc intervals. Baseline ECG values were defined as measurements taken at screening. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values.	Baseline (Screening), Week 2, 4, and 6
Secondary	Mean Maximum Plasma Concentration (Cmax) of GSK1278863 and GSK1278863 Metabolites	Cmax of GSK1278863 and GSK1278863 metabolites (M1, M2, M3, M4, M5 and M6) were reported. For assessment of Pharmacokinetics parameters blood samples were collected at Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1, 2 and 3 h after this first sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose).	Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1, 2 and 3 h after this first sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose).
Secondary	Mean Steady State Area Under the Curve (AUC) of GSK1278863 and GSK1278863 Metabolites	Mean Steady state AUC of GSK1278863 and GSK1278863 metabolites (M1, M2, M3, M4, M5 and M6) were reported. For pharmacokinetic parameter assessment blood samples were collected at Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1, 2 and 3 h after this fist sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose).	Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1, 2 and 3 h after this first sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose)

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