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CompletedNCT01587924Updated Nov 14, 2017Results posted

4 Week Switch Study in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease

A Phase 2 interventional study of GSK1278863 and rhEPO in Anaemia, sponsored by GlaxoSmithKline. Completed at 62 sites in 6 countries. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2017-11-14.

Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
80
Allocation
Randomized
Ages
18 Years to 99 Years
Sex
All
01

Study summary

This is a four-week, Phase IIa, randomized, active-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of switching subjects from stable rhEPO to GSK1278863 in approximately 68 hemodialysis-dependent subjects with anemia associated with chronic kidney disease. The study consists of a screening phase of 2 weeks, a 4-week treatment phase and a 2-week follow-up phase. The range of Hgb values for study eligibility is 9.5-12.0 g/dL and the subjects must have received the same rhEPO product with total weekly doses that varied by no more than 50% during the 4 weeks prior to the Screening visit (Week -1. This study aims to estimate the relationship between dose of GSK1278863 and Hgb response in hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease after switching from a stable maintenance dose of recombinant human erythropoetin (rhEPO).

Read the detailed description

This is a four-week, Phase IIa, randomized, active-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of switching subjects from stable rhEPO to GSK1278863 in approximately 68 hemodialysis-dependent subjects with anemia associated with chronic kidney disease. The study consists of a screening phase of 2 weeks, a 4-week treatment phase and a 2-week follow-up phase. The range of Hgb values for study eligibility is 9.5-12.0 g/dL and the subjects must have received the same rhEPO product with total weekly doses that varied by no more than 50% during the 4 weeks prior to the Screening visit (Week -1. Eligible subjects, stratified by their prior rhEPO dose will be randomized in equal proportions to receive double-blind GSK1278863 0.5 mg, 2 mg or 5 mg QD (after discontinuing their rhEPO), or to continue to receive their existing type and dose of rhEPO (epoetins or their biosimilars, or darbepoetin). Study treatment will be stopped if Hgb values fall outside of the protocol pre-specified ranges. Subject completion is defined as completion of all study phases including the follow-up phase.

This study aims to estimate the relationship between dose of GSK1278863 and Hgb response in hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease after switching from a stable maintenance dose of recombinant human erythropoetin (rhEPO). In addition, the study will characterize the effect of GSK1278863 on various pharmacokinetic (PK)/pharmacodynamic (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 if 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.

02

Conditions studied

  • Anaemia

Keywords

  • Renal Impairment
  • Anemia
  • pharmacokinetics
  • hemodialysis
  • Chronic kidney disease
  • GSK1278863
  • hemoglobin
  • Prolyl hydroxylase inhibitor
  • recombinant human erythropoietin
  • erythropoiesis stimulating agents
  • Dialysis, Renal
03

In context

Kidney Diseases

3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.

This study's enrollment of 80 is above the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.

Browse Kidney Diseases studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Age and weight: >/=18 years of age and >/=45 kg (weight post-dialysis).
  2. On three times weekly hemodialysis for at least 8 weeks, irrespective of eGFR values and stage of chronic kidney disease (CKD).
  3. A single-pool Kt/Vurea of >/=1.2 based on a historical value obtained within the prior month in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio (URR) of at least 65%.
  4. rhEPO use: Using the same rhEPO (epoetins or darbepoetin) with total weekly doses that varied by no more than 50% during the prior 4 weeks (i.e., maximum vs. minimum total weekly doses \</=50%).
  5. Hgb concentrations 9.5-12.0 g/dL (inclusive).
  6. Vitamin B12 above the lower limit of the reference range (may rescreen in two months).
  7. Folate: >/= 2.0 ng/mL (may rescreen in one month).
  8. Ferritin: >/=40 ng/mL with the absence of microcytic or hypochromic RBCs.
  9. Transferrin saturation (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 one of the 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)>40MIU/ml and estradiol \<40pg/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 enrolment. For most forms 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 one of the approved contraceptive methods from the time of Screening until completion of the Follow-up Visit.

Exclusion criteria

Exclusion Criteria:

  1. Dialysis modality: On peritoneal dialysis OR planned change in dialysis modality within the study time period.
  2. rhEPO Hyporesponders: As defined by an epoetin dose of >/=360 IU/kg/week IV or darbepoetin dose of >/=1.8 µg/kg/week IV within the prior 8 weeks.
  3. Renal transplant: Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant.
  4. Mircera or Peginesatide: Current or prior use (within the prior 8 weeks) of Mircera (methoxy polyethylene glycol epoetin beta) OR peginesatide.
  5. Total CPK: >5x the upper limit of the reference range.
  6. HIV: Positive HIV antibody.
  7. History of myocardial infarction or acute coronary syndrome within the prior 6 months.
  8. History of stroke or transient ischemic attacks (TIAs) within the prior 6 months.
  9. Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.

  10. Hypertension: Poorly controlled hypertension, whether due to inadequate treatment, or lack of treatment, is defined as follows:

    • DBP >100 mmHg or SBP>160 mmHg for subjects taking hypertension medication(s) before screening and dialysis, if required.
    • DBP >105 mmHg or SBP>170 mmHg for subjects who are asked to hold hypertension medication(s) before screening and dialysis.
  11. 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 except shunt thrombosis) within the prior 6 months.
  12. 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).
  13. Inflammatory disease: Chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease).
  14. Haematological disease: Any haematological 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, haematological malignancy, myeloma, haemolytic anemia) or any other cause of anemia other than renal disease.
  15. 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, alanine transaminase (ALT) or aspartate transaminase (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.
  16. Major surgery: (excluding vascular access surgery) Within the prior 12 weeks or planned during the study.
  17. Transfusion: Blood transfusion within the prior 12 weeks or an anticipated need for blood transfusion during the study.
  18. Ulcer and Active GI Bleeding: Evidence of active peptic, duodenal, or esophageal ulcer disease OR GI bleeding within the prior 12 weeks.
  19. 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).
  20. Malignancy: History of malignancy within the prior 5 years 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.
  21. Eyes: History of proliferative retinopathy requiring treatment within the prior 12 months or macular edema requiring treatment.
  22. Severe reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
  23. Drugs and supplements: Use of any prescription or non-prescription drugs or dietary supplements that are prohibited from Screening until the Follow-up Visit.
  24. Androgens: New androgen therapy or changes to pre-existing androgen regimen within the prior 12 weeks.
  25. Prior investigational product exposure: The Subject has participated in a clinical trial and has received an experimental investigational product within the prior 30 days.
  26. Protocol compliance: Unwillingness or inability to follow the procedures, or lifestyle and/or dietary restrictions outlined in the protocol.
  27. Other Conditions: Any condition which in the investigator's opinion should exclude the subject from participating in the study.
  28. Pregnancy or Lactation: Pregnant females as determined by positive serum hCG test OR women who are lactating at Screening or during the trial.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
80 participants (actual)

Study arms

  • Experimental
    0.5 mg GSK1278863

    once daily

    Drug: GSK1278863

  • Experimental
    2 mg GSK1278863

    once daily

    Drug: GSK1278863

  • Experimental
    5 mg GSK1278863

    once daily

    Drug: GSK1278863

  • Active comparator
    rhEPO

    as required

    Drug: rhEPO

Interventions

  • DrugGSK1278863

    tablet

  • DrugrhEPO

    injection

06

What researchers measure

Primary outcomes

  1. Modeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment

    Modeled Hgb change from Baseline over 4 weeks of treatment. Change from Baseline is the actual value of Hgb at Week 4 minus the Baseline value. For modeled change at Week 4 participants required a Baseline and two or more non missing post-baseline values. Baseline is the average of Week -2, -1 and Day 1 values. The model included fixed effects for Baseline Hgb, treatment, and treatment by day interaction. Covariate analysis for modeled Hgb change was performed. Random effects were fitted in the intercept and the slope over time.

    Time frame: Baseline (pre-dose on Day 1) and up to week 4

Secondary outcomes

  1. Hgb Variability Over 4 Weeks

    Within participant standard deviation for Hgb acts as a measure of Hgb variability. Hgb of participants was recorded over 4 weeks.

    Time frame: Up to 4 weeks

  2. Evaluation of Change From Baseline in Hepcidin Over Period

    Evaluation of change from baseline for hepcidin was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the last pre-dose value. Adjusted mean change from Baseline is presented as Least square (LS) mean.

    Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks

  3. Evaluation of Change From Baseline (Pre-dose on Day 1) in High Sensitivity C-Reactive Protein (hsCRP) Over 4 Weeks

    Evaluation of change from Baseline for hsCRP was analyzed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the last pre-dose value. Peak change from Baseline also was calculated; however adjusted mean change from Baseline has been presented here as LS means.

    Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks

  4. Change From Baseline for Erythropoeitin (EPO) Over Period

    Evaluation of change from Baseline (pre-dose on Day 1) for EPO was analyzed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the pre-dose Day 1 value. Adjusted means are presented as LS means.

    Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks

  5. Evaluation of Change From Baseline (Pre-dose on Day 1) for Peak Vascular Endothelial Growth Factor (VEGF) Over 4 Weeks

    Evaluation of change from Baseline for peak VEGF was analyzed up to 4 weeks. Baseline assessment was performed pre-dose on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Absolute mean change and peak change from Baseline in peak VGEF were also calculated; however, only model adjusted peak change in peak VGEF from Baseline has been presented as LS means.

    Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks

  6. Evaluation of Change From Baseline (Pre-dose on Day 1) for Hematocrit Over 4 Weeks

    Evaluation of change from Baseline for hematocrit over 4 weeks was performed. Change from Baseline is the value at indicated time point minus the Baseline value.

    Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks

  7. Residual Standard Deviation in Hgb (From the Linear Regression)

    Residual standard deviation was derived by linear regression. Hgb of participants was recorded over 4 weeks

    Time frame: Up to 4 weeks

  8. Number of Days Spent Within Hgb Range ( ±0.5 g/dL and ±1 g/dL ) From Baseline Hgb

    Time spent with Hgb within range (where range was defined as +-0.5 g/dL and +-1 g/dL from baseline Hgb ) was analyzed. Baseline value of Hgb was recorded pre-dose on Day 1.

    Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks

  9. Evaluation of Change From Baseline (Pre-dose on Day 1) in Ferritin Over 4 Weeks

    Change from Baseline (pre-dose on Day 1) in ferritin over 4 weeks was analyzed. Change from Baseline is the value at indicated time point minus the Baseline value. Model adjusted mean has been presented as LS mean.

    Time frame: Baseline (pre-dose on Day 1) and Week 4

  10. Evaluation of Change From Baseline (Pre-dose on Day 1) for Transferrin Over 4 Weeks

    Evaluation of change from Baseline for ferritin was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Model adjusted mean has been presented as LS mean.

    Time frame: Baseline (pre-dose on Day 1) and Week 4

  11. Change From Baseline (Pre-dose on Day 1) for Transferrin Saturation Over 4 Weeks

    Transferrin saturation is a medical laboratory test and is the ratio of serum iron and total iron-binding capacity, multiplied by 100 and expressed as a ratio. Evaluation of change from baseline for transferrin saturation was performed up to 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline value was recorded pre-dose on Day 1. Model adjusted mean values are presented as LS mean values.

    Time frame: Baseline (pre-dose on Day 1) and Week 4

  12. Change From Baseline (Pre-dose on Day 1) for Total Iron Over 4 Weeks

    Evaluation of change from Baseline for total iron was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was recorded pre-dose on Day 1. Adjusted mean was presented as LS mean.

    Time frame: Baseline (pre-dose on Day 1) and at Week 4

  13. Change From Baseline (Pre-dose on Day 1) in Total Iron Binding Capacity Over 4 Weeks

    Evaluation of change from Baseline in total iron binding capacity was performed over 4 weeks. Baseline was recorded pre-dose on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Adjusted means are presented as LS means.

    Time frame: Baseline (pre-dose on Day 1) and Week 4

  14. Change From Baseline (Pre-dose on Day 1) for Red Blood Cells (RBCs) Over 4 Weeks

    Change from Baseline in RBCs was a pharmacodynamic (PD) biomarker. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was recorded pre-dose on Day 1. Change from Baseline (pre-dose on Day 1) in RBCs was calculated over 4 weeks.

    Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks

  15. Change From Baseline (Pre-dose on Day 1) for Reticulocytes Over 4 Weeks

    Evaluation of change from Baseline for reticulocytes was a PD parameter. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline value was recorded pre-dose on Day 1.

    Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks

  16. Number of Participants Reaching Hgb Stopping Criteria

    Participants were analyzed whether they had any increase or decrease from the Baseline Hgb. Hgb increase based stopping criteria included analysis of Increase or decrease of more than or equal to (\>=) 2 g/dL from the Baseline (pre-dose on Day 1) was recorded and also the participants with hemoglobin \>=13 g/dL were recorded.

    Time frame: Up to 4 weeks

  17. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. An SAE is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above. Only on-treatment data has been presented.

    Time frame: Up to 4 weeks

  18. Number of Participants Discontinuing the Study Treatment Due to AEs

    Discontinuation of the study drug could be due to safety-related reasons AE. The AEs responsible included anemia, gastrointestinal hemorrhage, and nausea.

    Time frame: Up to 4 weeks

  19. Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks

    Each of the plasma concentration-time plot contained one plot on the untransformed scale (i.e. a linear plot) and one plot on the log transformed scale (i.e. log-linear plot). Plasma concentrations were analyzed for the study drug (GSK1278863), and its metabolites namely GSK2391220 (M2), GSK2531403 (M3), GSK2487818A (M4), GSK2506102A (M5), GSK2531398 (M6), and GSK2531401A (M13). Pharmacokinetic analysis was done on Weeks (W) 2 and 4 at a fixed timely interval of 5 hours (h) on W2 and every hour on W4. Only the data for last visit for W2 and last visit of W4 has been presented.

    Time frame: Up to 4 weeks

  20. Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Concern (PCI)

    Participants were analyzed up to 6 weeks for hematological and clinical chemistry parameters of PCI whether they had any higher or lower values than the reference range post screening. Normal alkaline phosphatase (ALP) was 0-46 U/L, aspartate amino transferase (AST) 0-42 U/L, ALP 20-125 U/L, total bilirubin 0-1.3 mg/dL, troponin 0-0.1ng/mL, Hgb 12 - 16 g/dL, platelets 140-450 G/L, creatine phosphokinase 29-168 U/L, creatinine 0.57 - 1.25 mg/dL, Potassium 3.6-5.0 mmol/L, hematocrit 38-45%; however, no participants with abnormal hematology and clinical chemistry parameters were recorded.

    Time frame: Up to 6 weeks (including follow-up)

  21. Number of Participants With Abnormal Vital Signs of PCI

    Vital signs include systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Three measurements of SBP, DBP and HR were recorded from the participant in a supine position for at least 5 minutes (allowing enough time between measurement to completely deflate and loosen the inflatable cuff). Data has been presented for vital signs with values high and low from the reference range.

    Time frame: Up to 6 weeks

  22. Number of Participants With Electrocardiogram (ECG) Findings Over Period

    Participants were analyzed for any abnormality in ECG and was categorized as abnormal clinically significant and abnormal and clinically insignificant. The parameters that were analyzed for ECG were atrial fibrillation, Atrial premature complex, Bigeminy, First degree AV block (PR interval \> 200 msec), Incomplete right bundle branch block, Junctional rhythm, Junctional tachycardia (heart rate \>100 beats/min), Left anterior hemi block (synonymous to left anterior fascicular block), Left atrial abnormality, Left axis deviation (QRS axis more negative than -30 degrees), Left bundle branch block, Left ventricular hypertrophy, Myocardial infarction, anterior, Myocardial infarction, inferior, Non-specific ST-T changes, Normal sinus rhythm, Poor R wave progression, Right atrial abnormality, Right QRS axis deviation, bundle block, ventricular hypertrophy, ST depression or abnormality, AV block, arrhythmia, short PR interval, bradycardia, tachycardia, and T-wave abnormality.

    Time frame: Up to 6 weeks

07

Results

Posted Sep 12, 2017

Participant flow

This study was conducted in hemodialysis-dependent (HDD) participants from 06 June 2012 till 17 June 2013 across 48 centers in the United States (US), Canada, and European Union. A total of 68 participants were planned to be enrolled.

Participant flow — Overall Study
Milestone0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Started21212120
Completed17171719
Not completed4441
Withdrew: Adverse event0200
Withdrew: Protocol violation2121
Withdrew: Met hemoglobin stopping criteria2010
Withdrew: Withdrawal by subject0110

Outcome measures

PrimaryModeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment

Modeled Hgb change from Baseline over 4 weeks of treatment. Change from Baseline is the actual value of Hgb at Week 4 minus the Baseline value. For modeled change at Week 4 participants required a Baseline and two or more non missing post-baseline values. Baseline is the average of Week -2, -1 and Day 1 values. The model included fixed effects for Baseline Hgb, treatment, and treatment by day interaction. Covariate analysis for modeled Hgb change was performed. Random effects were fitted in the intercept and the slope over time.

Time frame:
Baseline (pre-dose on Day 1) and up to week 4
Reported as:
Mean · Grams per deciliter (g/dL)
Modeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment
Grams per deciliter (g/dL)0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Modeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment-1.130 ± 0.6830-1.070 ± 0.77030.212 ± 0.7521-0.273 ± 0.6335
Statistical analysis
  • 0.5 mg GSK1278863 vs 2 mg GSK1278863 vs 5 mg GSK1278863 vs rhEPO · Regression, Linear · p = 0.0135 (The p-value is showing the interaction of each subgroup by treatment and by day)
  • 0.5 mg GSK1278863 vs 2 mg GSK1278863 vs 5 mg GSK1278863 vs rhEPO · Regression, Linear · p = 0.5082 (The p-value is showing the interaction of each subgroup by treatment and by day)
  • 0.5 mg GSK1278863 vs 2 mg GSK1278863 vs 5 mg GSK1278863 vs rhEPO · Regression, Linear · p = 0.9770 (The p-value is showing the interaction of each subgroup by treatment and by day)
  • 0.5 mg GSK1278863 vs 2 mg GSK1278863 vs 5 mg GSK1278863 vs rhEPO · Regression, Linear · p = 0.0618 (The p-value is showing the interaction of each subgroup by treatment and by day)
  • 0.5 mg GSK1278863 vs 2 mg GSK1278863 vs 5 mg GSK1278863 vs rhEPO · Regression, Linear · p = 0.7495 (The p-value is showing the interaction of each subgroup by treatment and by day)
  • 0.5 mg GSK1278863 vs 2 mg GSK1278863 vs 5 mg GSK1278863 vs rhEPO · Regression, Linear · p = 0.7865 (The p-value is showing the interaction of each subgroup by treatment and by day)
  • 0.5 mg GSK1278863 vs 2 mg GSK1278863 vs 5 mg GSK1278863 vs rhEPO · Regression, Linear · p = 0.0622 (The p-value is showing the interaction of each subgroup by treatment and by day)
  • 0.5 mg GSK1278863 vs 2 mg GSK1278863 vs 5 mg GSK1278863 vs rhEPO · Regression, Linear · p = 0.2044 (The p-value is showing the interaction of each subgroup by treatment and by day)
  • 0.5 mg GSK1278863 vs 2 mg GSK1278863 vs 5 mg GSK1278863 vs rhEPO · Regression, Linear · p = 0.8537 (The p-value is showing the interaction of each subgroup by treatment and by day)
SecondaryHgb Variability Over 4 Weeks

Within participant standard deviation for Hgb acts as a measure of Hgb variability. Hgb of participants was recorded over 4 weeks.

Time frame:
Up to 4 weeks
Reported as:
Mean · g/dL
Hgb Variability Over 4 Weeks
g/dL0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Hgb Variability Over 4 Weeks0.53 ± 0.2710.55 ± 0.3250.40 ± 0.3640.35 ± 0.193
SecondaryEvaluation of Change From Baseline in Hepcidin Over Period

Evaluation of change from baseline for hepcidin was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the last pre-dose value. Adjusted mean change from Baseline is presented as Least square (LS) mean.

Time frame:
Baseline (pre-dose on Day 1) and up to 4 weeks
Reported as:
Least squares mean · Micrograms per liter (mcg/L)
Evaluation of Change From Baseline in Hepcidin Over Period
Micrograms per liter (mcg/L)0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Evaluation of Change From Baseline in Hepcidin Over Period204.88 ± 60.741150.29 ± 62.61916.42 ± 62.815-45.47 ± 61.939
SecondaryEvaluation of Change From Baseline (Pre-dose on Day 1) in High Sensitivity C-Reactive Protein (hsCRP) Over 4 Weeks

Evaluation of change from Baseline for hsCRP was analyzed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the last pre-dose value. Peak change from Baseline also was calculated; however adjusted mean change from Baseline has been presented here as LS means.

Time frame:
Baseline (pre-dose on Day 1) and up to 4 weeks
Reported as:
Least squares mean · Milligrams per liter (mg/L)
Evaluation of Change From Baseline (Pre-dose on Day 1) in High Sensitivity C-Reactive Protein (hsCRP) Over 4 Weeks
Milligrams per liter (mg/L)0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Evaluation of Change From Baseline (Pre-dose on Day 1) in High Sensitivity C-Reactive Protein (hsCRP) Over 4 Weeks-0.40 ± 1.784-4.76 ± 1.834-1.48 ± 1.886-2.92 ± 1.784
SecondaryChange From Baseline for Erythropoeitin (EPO) Over Period

Evaluation of change from Baseline (pre-dose on Day 1) for EPO was analyzed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the pre-dose Day 1 value. Adjusted means are presented as LS means.

Time frame:
Baseline (pre-dose on Day 1) and up to 4 weeks
Reported as:
Least squares mean · Units per liter (U/L)
Change From Baseline for Erythropoeitin (EPO) Over Period
Units per liter (U/L)0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Change From Baseline for Erythropoeitin (EPO) Over Period4.368 ± 73.34853.263 ± 73.5023181.948 ± 77.7763393.159 ± 71.4855
SecondaryEvaluation of Change From Baseline (Pre-dose on Day 1) for Peak Vascular Endothelial Growth Factor (VEGF) Over 4 Weeks

Evaluation of change from Baseline for peak VEGF was analyzed up to 4 weeks. Baseline assessment was performed pre-dose on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Absolute mean change and peak change from Baseline in peak VGEF were also calculated; however, only model adjusted peak change in peak VGEF from Baseline has been presented as LS means.

Time frame:
Baseline (pre-dose on Day 1) and up to 4 weeks
Reported as:
Least squares mean · Nanograms per liter (ng/L)
Evaluation of Change From Baseline (Pre-dose on Day 1) for Peak Vascular Endothelial Growth Factor (VEGF) Over 4 Weeks
Nanograms per liter (ng/L)0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Evaluation of Change From Baseline (Pre-dose on Day 1) for Peak Vascular Endothelial Growth Factor (VEGF) Over 4 Weeks23.21 ± 12.11021.52 ± 12.29153.85 ± 12.64520.59 ± 12.874
SecondaryEvaluation of Change From Baseline (Pre-dose on Day 1) for Hematocrit Over 4 Weeks

Evaluation of change from Baseline for hematocrit over 4 weeks was performed. Change from Baseline is the value at indicated time point minus the Baseline value.

Time frame:
Baseline (pre-dose on Day 1) and up to 4 weeks
Reported as:
Mean · Percentage
Evaluation of Change From Baseline (Pre-dose on Day 1) for Hematocrit Over 4 Weeks
Percentage0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Week 1-0.59 ± 1.609-0.16 ± 1.823-0.75 ± 1.7350.20 ± 1.738
Week 2-1.33 ± 2.122-1.56 ± 2.296-0.75 ± 1.9602.02 ± 8.248
Week 3-2.32 ± 2.634-2.22 ± 2.712-0.65 ± 2.2770.24 ± 2.507
Week 4-3.22 ± 2.731-2.63 ± 3.006-0.33 ± 2.044-0.22 ± 2.874
SecondaryResidual Standard Deviation in Hgb (From the Linear Regression)

Residual standard deviation was derived by linear regression. Hgb of participants was recorded over 4 weeks

Time frame:
Up to 4 weeks
Reported as:
Mean · g/L
Residual Standard Deviation in Hgb (From the Linear Regression)
g/L0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Residual Standard Deviation in Hgb (From the Linear Regression)0.24 ± 0.1080.26 ± 0.1150.26 ± 0.3090.20 ± 0.112
SecondaryNumber of Days Spent Within Hgb Range ( ±0.5 g/dL and ±1 g/dL ) From Baseline Hgb

Time spent with Hgb within range (where range was defined as +-0.5 g/dL and +-1 g/dL from baseline Hgb ) was analyzed. Baseline value of Hgb was recorded pre-dose on Day 1.

Time frame:
Baseline (pre-dose on Day 1) and up to 4 weeks
Reported as:
Median · Days
Number of Days Spent Within Hgb Range ( ±0.5 g/dL and ±1 g/dL ) From Baseline Hgb
Days0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Within +/- 0.5 g/dL12.82 (6.98 to 21.85)14.34 (4.86 to 25.76)24.41 (8.94 to 28.00)21.15 (10.50 to 28.00)
Within +/- 1 g/dL27.71 (19.25 to 28.00)20.79 (12.76 to 28.00)28.00 (24.77 to 28.00)28.00 (23.33 to 28.00)
SecondaryEvaluation of Change From Baseline (Pre-dose on Day 1) in Ferritin Over 4 Weeks

Change from Baseline (pre-dose on Day 1) in ferritin over 4 weeks was analyzed. Change from Baseline is the value at indicated time point minus the Baseline value. Model adjusted mean has been presented as LS mean.

Time frame:
Baseline (pre-dose on Day 1) and Week 4
Reported as:
Least squares mean · Micrograms per liter
Evaluation of Change From Baseline (Pre-dose on Day 1) in Ferritin Over 4 Weeks
Micrograms per liter0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Evaluation of Change From Baseline (Pre-dose on Day 1) in Ferritin Over 4 Weeks76.7 ± 36.31-1.6 ± 37.41-76.7 ± 38.48-38.0 ± 37.27
SecondaryEvaluation of Change From Baseline (Pre-dose on Day 1) for Transferrin Over 4 Weeks

Evaluation of change from Baseline for ferritin was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Model adjusted mean has been presented as LS mean.

Time frame:
Baseline (pre-dose on Day 1) and Week 4
Reported as:
Least squares mean · Grams per liter
Evaluation of Change From Baseline (Pre-dose on Day 1) for Transferrin Over 4 Weeks
Grams per liter0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Evaluation of Change From Baseline (Pre-dose on Day 1) for Transferrin Over 4 Weeks0.105 ± 0.06990.155 ± 0.07190.221 ± 0.07370.059 ± 0.0703
SecondaryChange From Baseline (Pre-dose on Day 1) for Transferrin Saturation Over 4 Weeks

Transferrin saturation is a medical laboratory test and is the ratio of serum iron and total iron-binding capacity, multiplied by 100 and expressed as a ratio. Evaluation of change from baseline for transferrin saturation was performed up to 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline value was recorded pre-dose on Day 1. Model adjusted mean values are presented as LS mean values.

Time frame:
Baseline (pre-dose on Day 1) and Week 4
Reported as:
Least squares mean · Ratio
Change From Baseline (Pre-dose on Day 1) for Transferrin Saturation Over 4 Weeks
Ratio0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Change From Baseline (Pre-dose on Day 1) for Transferrin Saturation Over 4 Weeks6.4 ± 3.3311.7 ± 3.341.3 ± 3.42-0.1 ± 3.24
SecondaryChange From Baseline (Pre-dose on Day 1) for Total Iron Over 4 Weeks

Evaluation of change from Baseline for total iron was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was recorded pre-dose on Day 1. Adjusted mean was presented as LS mean.

Time frame:
Baseline (pre-dose on Day 1) and at Week 4
Reported as:
Least squares mean · Micromoles per Liter
Change From Baseline (Pre-dose on Day 1) for Total Iron Over 4 Weeks
Micromoles per Liter0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Change From Baseline (Pre-dose on Day 1) for Total Iron Over 4 Weeks4.3 ± 1.446.2 ± 1.472.5 ± 1.510.3 ± 1.43
SecondaryChange From Baseline (Pre-dose on Day 1) in Total Iron Binding Capacity Over 4 Weeks

Evaluation of change from Baseline in total iron binding capacity was performed over 4 weeks. Baseline was recorded pre-dose on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Adjusted means are presented as LS means.

Time frame:
Baseline (pre-dose on Day 1) and Week 4
Reported as:
Least squares mean · Micromoles per Liter
Change From Baseline (Pre-dose on Day 1) in Total Iron Binding Capacity Over 4 Weeks
Micromoles per Liter0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Change From Baseline (Pre-dose on Day 1) in Total Iron Binding Capacity Over 4 Weeks3.2 ± 1.053.7 ± 1.065.2 ± 1.081.3 ± 1.03
SecondaryChange From Baseline (Pre-dose on Day 1) for Red Blood Cells (RBCs) Over 4 Weeks

Change from Baseline in RBCs was a pharmacodynamic (PD) biomarker. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was recorded pre-dose on Day 1. Change from Baseline (pre-dose on Day 1) in RBCs was calculated over 4 weeks.

Time frame:
Baseline (pre-dose on Day 1) and up to 4 weeks
Reported as:
Mean · 10^12 cells per Liter (Giga cells per L)
Change From Baseline (Pre-dose on Day 1) for Red Blood Cells (RBCs) Over 4 Weeks
10^12 cells per Liter (Giga cells per L)0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Week 1-0.04 ± 0.157-0.03 ± 0.189-0.06 ± 0.1840.02 ± 0.177
Week 2-0.13 ± 0.191-0.14 ± 0.243-0.05 ± 0.2100.18 ± 0.771
Week 3-0.22 ± 0.248-0.19 ± 0.305-0.05 ± 0.2290.01 ± 0.256
Week 4-0.29 ± 0.259-0.25 ± 0.337-0.03 ± 0.198-0.03 ± 0.262
SecondaryChange From Baseline (Pre-dose on Day 1) for Reticulocytes Over 4 Weeks

Evaluation of change from Baseline for reticulocytes was a PD parameter. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline value was recorded pre-dose on Day 1.

Time frame:
Baseline (pre-dose on Day 1) and up to 4 weeks
Reported as:
Mean · Percentage change
Change From Baseline (Pre-dose on Day 1) for Reticulocytes Over 4 Weeks
Percentage change0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Week 1-0.42 ± 0.966-0.56 ± 0.7510.03 ± 0.681-0.08 ± 0.837
Week 2-0.45 ± 1.072-0.49 ± 0.613-0.08 ± 0.656-0.14 ± 0.737
Week 3-0.34 ± 1.114-0.27 ± 0.757-0.06 ± 0.634-0.35 ± 0.782
Week 4-0.36 ± 1.030-0.26 ± 0.533-0.03 ± 0.703-0.29 ± 0.686
SecondaryNumber of Participants Reaching Hgb Stopping Criteria

Participants were analyzed whether they had any increase or decrease from the Baseline Hgb. Hgb increase based stopping criteria included analysis of Increase or decrease of more than or equal to (\>=) 2 g/dL from the Baseline (pre-dose on Day 1) was recorded and also the participants with hemoglobin \>=13 g/dL were recorded.

Time frame:
Up to 4 weeks
Reported as:
Count of participants · Participants
Number of Participants Reaching Hgb Stopping Criteria
Participants0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Post Baseline Hgb <8.01100
>=2g/dL Hgb increase post Baseline0110
Post Baseline Hgb >=13.00010
SecondaryNumber of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. An SAE is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above. Only on-treatment data has been presented.

Time frame:
Up to 4 weeks
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Any AE9716
Any SAE0202
SecondaryNumber of Participants Discontinuing the Study Treatment Due to AEs

Discontinuation of the study drug could be due to safety-related reasons AE. The AEs responsible included anemia, gastrointestinal hemorrhage, and nausea.

Time frame:
Up to 4 weeks
Reported as:
Count of participants · Participants
Number of Participants Discontinuing the Study Treatment Due to AEs
Participants0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Number of Participants Discontinuing the Study Treatment Due to AEs1200
SecondaryMean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks

Each of the plasma concentration-time plot contained one plot on the untransformed scale (i.e. a linear plot) and one plot on the log transformed scale (i.e. log-linear plot). Plasma concentrations were analyzed for the study drug (GSK1278863), and its metabolites namely GSK2391220 (M2), GSK2531403 (M3), GSK2487818A (M4), GSK2506102A (M5), GSK2531398 (M6), and GSK2531401A (M13). Pharmacokinetic analysis was done on Weeks (W) 2 and 4 at a fixed timely interval of 5 hours (h) on W2 and every hour on W4. Only the data for last visit for W2 and last visit of W4 has been presented.

Time frame:
Up to 4 weeks
Reported as:
Mean · Nanograms per milliliter (ng/mL)
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks
Nanograms per milliliter (ng/mL)0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863
GSK1278863, Week 2, 7-11h0.2292 ± 0.400313.3148 ± 5.895405.6170 ± 15.91725
GSK1278863, Week 4, 3h3.3113 ± 3.1433617.9009 ± 12.8991734.7253 ± 38.79049
M2, Week 2, 7-11h0.4582 ± 0.283401.5468 ± 1.116794.3165 ± 3.03668
M2, Week 4, 3h0.6780 ± 0.424932.0382 ± 1.985347.4288 ± 3.64287
M3, Week 2, 7-11h0.6386 ± 0.359402.1188 ± 1.607715.6935 ± 3.24262
M3, Week 4, 3h0.7921 ± 0.427852.2857 ± 2.039688.4582 ± 3.55548
M4, Week 2, 7-11h0.2156 ± 0.194300.8121 ± 0.696222.3216 ± 2.75137
M4, Week 4, 3h0.6016 ± 0.455511.8355 ± 1.896436.1856 ± 3.24320
M5, Week 2, 7-11h0.1546 ± 0.116790.5511 ± 0.410771.4581 ± 0.71612
M5, Week 4, 3h0.1995 ± 0.224530.7132 ± 1.082881.9972 ± 0.71061
M6, Week 2, 7-11h0.1776 ± 0.121400.6956 ± 0.475611.8957 ± 1.47442
M6, Week 4, 3h0.3235 ± 0.278451.0626 ± 1.358953.4569 ± 1.56093
M13, Week 2, 7-11h0.4875 ± 0.385991.4014 ± 1.190963.9647 ± 1.86947
M13, Week 4, 3h0.4651 ± 0.354421.3623 ± 1.403245.3494 ± 2.60236
SecondaryNumber of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Concern (PCI)

Participants were analyzed up to 6 weeks for hematological and clinical chemistry parameters of PCI whether they had any higher or lower values than the reference range post screening. Normal alkaline phosphatase (ALP) was 0-46 U/L, aspartate amino transferase (AST) 0-42 U/L, ALP 20-125 U/L, total bilirubin 0-1.3 mg/dL, troponin 0-0.1ng/mL, Hgb 12 - 16 g/dL, platelets 140-450 G/L, creatine phosphokinase 29-168 U/L, creatinine 0.57 - 1.25 mg/dL, Potassium 3.6-5.0 mmol/L, hematocrit 38-45%; however, no participants with abnormal hematology and clinical chemistry parameters were recorded.

Time frame:
Up to 6 weeks (including follow-up)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Concern (PCI)
Participants0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Concern (PCI)0000
SecondaryNumber of Participants With Abnormal Vital Signs of PCI

Vital signs include systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Three measurements of SBP, DBP and HR were recorded from the participant in a supine position for at least 5 minutes (allowing enough time between measurement to completely deflate and loosen the inflatable cuff). Data has been presented for vital signs with values high and low from the reference range.

Time frame:
Up to 6 weeks
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Vital Signs of PCI
Participants0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
DBP, low1223
DBP, high2202
SBP, low0101
SBP, high109610
HR, low0000
HR, high0032
SecondaryNumber of Participants With Electrocardiogram (ECG) Findings Over Period

Participants were analyzed for any abnormality in ECG and was categorized as abnormal clinically significant and abnormal and clinically insignificant. The parameters that were analyzed for ECG were atrial fibrillation, Atrial premature complex, Bigeminy, First degree AV block (PR interval \> 200 msec), Incomplete right bundle branch block, Junctional rhythm, Junctional tachycardia (heart rate \>100 beats/min), Left anterior hemi block (synonymous to left anterior fascicular block), Left atrial abnormality, Left axis deviation (QRS axis more negative than -30 degrees), Left bundle branch block, Left ventricular hypertrophy, Myocardial infarction, anterior, Myocardial infarction, inferior, Non-specific ST-T changes, Normal sinus rhythm, Poor R wave progression, Right atrial abnormality, Right QRS axis deviation, bundle block, ventricular hypertrophy, ST depression or abnormality, AV block, arrhythmia, short PR interval, bradycardia, tachycardia, and T-wave abnormality.

Time frame:
Up to 6 weeks
Reported as:
Count of participants · Participants
Number of Participants With Electrocardiogram (ECG) Findings Over Period
Participants0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
Abnormal, clinically significant1012812
Abnormal, not clinically significant5696

Adverse events

Collected over Up to 4 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
0.5 mg GSK12788630/21 (0%)0/21 (0%)3/21 (14.3%)
2 mg GSK12788630/21 (0%)2/21 (9.5%)1/21 (4.8%)
5 mg GSK12788630/20 (0%)0/20 (0%)0/20 (0%)
rhEPO0/20 (0%)2/20 (10%)0/20 (0%)
Most frequent serious events
Most frequent serious events
Event0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
HyperkalemiaMetabolism and nutrition disorders0/210/210/201/20
Pulmonary edemaRespiratory, thoracic and mediastinal disorders0/210/210/201/20
ConstipationGastrointestinal disorders0/211/210/200/20
Gastrointestinal hemorrhageGastrointestinal disorders0/211/210/200/20
Most frequent other events
Most frequent other events
Event0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPO
AnemiaBlood and lymphatic system disorders3/211/210/200/20

Baseline characteristics

The intent to treat (ITT) population included all randomized participants who received at least one dose of the study drug, had a baseline and at least one corresponding on treatment laboratory assessment.

Age, Continuous
Age, Continuous(Years)0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPOTotal
Mean56.4 ± 16.8054.7 ± 18.7855.9 ± 18.3764.2 ± 12.7757.8 ± 16.92
Sex: Female, Male
Sex: Female, Male(Participants)0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPOTotal
Female378422
Male1813111658
Race (NIH/OMB)
Race (NIH/OMB)(Participants)0.5 mg GSK12788632 mg GSK12788635 mg GSK1278863rhEPOTotal
American Indian or Alaska Native00101
Asian03205
Native Hawaiian or Other Pacific Islander00000
Black or African American734418
White1414121454
More than one race00022
Unknown or Not Reported00000
08

Study locations

62 sites
  • GSK Investigational Site
    Paragould, Arizona 72450, United States
  • GSK Investigational Site
    Tempe, Arizona 85284, United States
  • GSK Investigational Site
    Pine Bluff, Arkansas 71603, United States
  • GSK Investigational Site
    Azusa, California 91702, United States
  • GSK Investigational Site
    Bakersfield, California 93308, United States
  • GSK Investigational Site
    Bakersfield, California 93309, United States
  • GSK Investigational Site
    Los Angeles, California 90022, United States
  • GSK Investigational Site
    Los Angeles, California 90025-4837, United States
  • GSK Investigational Site
    Los Angeles, California 90057, United States
  • GSK Investigational Site
    Lynwood, California 60262, United States
  • GSK Investigational Site
    Orange, California 92868, United States
  • GSK Investigational Site
    Riverside, California 92505, United States
  • GSK Investigational Site
    West Hills, California 91307, United States
  • GSK Investigational Site
    Whittier, California 90603, United States
  • GSK Investigational Site
    Arvada, Colorado 80002, United States
  • GSK Investigational Site
    Denver, Colorado 80230, United States
  • GSK Investigational Site
    Westminster, Colorado 80031, United States
  • GSK Investigational Site
    Waterbury, Connecticut 06708, United States
  • GSK Investigational Site
    Coral Springs, Florida 33071, United States
  • GSK Investigational Site
    Miami, Florida 33145, United States
  • GSK Investigational Site
    Miami, Florida 33150, United States
  • GSK Investigational Site
    Pembroke Pines, Florida 33028, United States
  • GSK Investigational Site
    Spring Hill, Florida 34608, United States
  • GSK Investigational Site
    Macon, Georgia 31217, United States
  • GSK Investigational Site
    Gurnee, Illinois 60031, United States
  • GSK Investigational Site
    Bethesda, Maryland 20814, United States
  • GSK Investigational Site
    Detroit, Michigan 48236, United States
  • GSK Investigational Site
    Southgate, Michigan 48195, United States
  • GSK Investigational Site
    Las Vegas, Nevada 89106, United States
  • GSK Investigational Site
    Brooklyn, New York 11212, United States
  • GSK Investigational Site
    Asheville, North Carolina NC 28805, United States
  • GSK Investigational Site
    Charlotte, North Carolina, United States
  • GSK Investigational Site
    Durham, North Carolina 27704, United States
  • GSK Investigational Site
    Winston-Salem, North Carolina 27101, United States
  • GSK Investigational Site
    Oklahoma City, Oklahoma 73116, United States
  • GSK Investigational Site
    Erie, Pennsylvania 16507, United States
  • GSK Investigational Site
    Arlington, Texas 76011, United States
  • GSK Investigational Site
    Greenville, Texas 75402, United States
  • GSK Investigational Site
    Houston, Texas 77004, United States
  • GSK Investigational Site
    Houston, Texas 77091, United States
  • GSK Investigational Site
    Killeen, Texas TX 76543, United States
  • GSK Investigational Site
    San Antonio, Texas 78229, United States
  • GSK Investigational Site
    Calgary, Alberta T2R 0X7, Canada
  • GSK Investigational Site
    Edmonton, Alberta T6G 2B7, Canada
  • GSK Investigational Site
    Halifax, Nova Scotia B3H 1V7, Canada
  • GSK Investigational Site
    London, Ontario N6A 5A5, Canada
  • GSK Investigational Site
    Sudbury, Ontario P3E 5J1, Canada
  • GSK Investigational Site
    Aalborg, DK-9000, Denmark
  • GSK Investigational Site
    Odense, DK-5000, Denmark
  • GSK Investigational Site
    Roskilde, DK-4000, Denmark
  • GSK Investigational Site
    Heidelberg, Baden-Wuerttemberg 69120, Germany
  • GSK Investigational Site
    Aschaffenburg, Bayern 63741, Germany
  • GSK Investigational Site
    Oberschleissheim, Bayern 85764, Germany
  • GSK Investigational Site
    Demmin, Mecklenburg-Vorpommern 17109, Germany
  • GSK Investigational Site
    Lehrte, Niedersachsen 31275, Germany
  • GSK Investigational Site
    Koeln, Nordrhein-Westfalen 50937, Germany
  • GSK Investigational Site
    Hamburg, 22297, Germany
  • GSK Investigational Site
    Oslo, 0027, Norway
  • GSK Investigational Site
    Oslo, 0405, Norway
  • GSK Investigational Site
    Karlstad, SE-651 85, Sweden
  • GSK Investigational Site
    Stockholm, SE-141 86, Sweden
  • GSK Investigational Site
    Uppsala, SE-751 85, Sweden
09

References and documents

Publications

  • Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2. PubMed 36005278 ↗
  • Holdstock L, Meadowcroft AM, Maier R, Johnson BM, Jones D, Rastogi A, Zeig S, Lepore JJ, Cobitz AR. Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia. J Am Soc Nephrol. 2016 Apr;27(4):1234-44. doi: 10.1681/ASN.2014111139. Epub 2015 Oct 22. PubMed 26494831 ↗

Individual participant data

Plan to share: Yes — Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 14, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01587924
Lead sponsor
GlaxoSmithKline
Collaborators
PPD DEVELOPMENT, LP
Responsible party
Sponsor
First posted
Apr 30, 2012
Start date
May 23, 2012
Primary completion
May 27, 2013
Completion
May 27, 2013
Results posted
Sep 12, 2017
Last update
Nov 14, 2017

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Aug 2017. You cannot join it, but the record below documents what was studied.

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