A Study to Evaluate Safety and Efficacy of GSK1278863 in Non-Dialysis Dependent (NDD) Subjects With Anemia Associated With Chronic Kidney Diseases (CKD)
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT01977573
Collaborator
(none)
252
123
2
19.4
2
0.1
Study Details
Study Description
Brief Summary
This study will be conducted in approximately 228 subjects with anemia associated with CKD who are not on dialysis. Two groups of subjects will be enrolled into the study: Group 1: recombinant human erythropoietin (rhEPO) naive subjects; Group 2: rhEPO users, who are currently receiving rhEPO. Subjects who are rhEPO naive will be randomized to receive either GSK1278863 once daily (QD) or rhEPO in a 3:1 fashion; subjects who are receiving an rhEPO before enrolling (rhEPO users) will be randomized in a 1:1 fashion to GSK1278863 QD or to the control arm. For those randomized to the control arm, the decision around whether the subject requires rhEPO, the selection of the type of rhEPO (if needed) and the choice of rhEPO dose to achieve and maintain Hgb concentrations within the target range should be based on Investigator clinical judgment, with the historical rhEPO dose and the current Hgb value being considered. The study consists of a screening phase of at least 4 weeks, a 24-week treatment phase and a follow-up visit that will occur approximately 4 weeks after completing treatment. It is anticipated that the data generated will enable selection of the starting dose(s) and optimize dose adjustment regimen(s) for Phase 3 clinical trials.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
252 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
A 24-week, Phase IIB, Randomized, Controlled, Parallel Group, Multi-center Study to Evaluate the Safety and Efficacy of GSK1278863 in Subjects With Anemia Associated With Chronic Kidney Diseases Who Are Not on Dialysis.
Study Start Date
:
Oct 31, 2013
Actual Primary Completion Date
:
May 1, 2015
Actual Study Completion Date
:
Jun 15, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GSK1278863 Subjects will be administered GSK1278863 QD. Starting dose will be based on data from previous studies with GSK1278863 and dose-response modelling, as well as Baseline Hgb concentration. After 4 Week of fixed dose period, dose may be adjusted to achieve Hgb 9.0 to 10.5 g/dL |
Drug: GSK1278863
Film-coated tablets containing 0.5 mg, 1 mg, 2 mg, 5mg or matching placebo
|
| Other: Control All subjects who are randomized to the Control arm will receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, to maintain Hgb levels within the target range. The decision around whether a subject requires rhEPO, selection of the type of rhEPO and rhEPO dose should be based on Investigator clinical judgment, with the historical rhEPO dose (where applicable) and the current Hgb value being considered. |
Drug: rhEPO
Locally sourced rhEPO. All subjects who are randomized to the Control arm will receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, to maintain Hgb levels within the target range. The decision around whether a subject requires rhEPO, selection of the type of rhEPO and rhEPO dose should be based on Investigator clinical judgment, with the historical rhEPO dose (where applicable) and the current Hgb value being considered..
|
Outcome Measures
Primary Outcome Measures
- Summary of Hemoglobin (Hgb) Concentration at Week 24 [Week 24]
The original Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-10.0 g/dL (8.0-10.0 g/dL USA site only) and for Group 2- rhEPO users with a stable baseline Hgb of 9.0-10.5 g/dL (9.0-10.5 g/dL USA site only); the Hgb target range was 9.0 to 10.5 g/dL (9.0-10.5 g/dL USA site only). The study amended Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-11.0 g/dL and Group 2- rhEPO users with a stable baseline Hgb of 9.0-11.5 g/dL; Hgb target range - 10.0 to 11.5 g/dL. Data are presented for those participants following the original criteria ("Original") and those following the amended ("Amended") criteria. The primary objective was to characterize the ability of GSK1278863 to achieve mean Hgb response within the target range.
Secondary Outcome Measures
- Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24 [Week 24]
Target range is defined as: Original Hgb Criteria of 9.0 to 10.5 gram/deciliter (g/dL), and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL.
- Number of Participants Reaching Pre-defined Hgb Stopping Criteria [Over a period of 24 Weeks]
The Hgb stopping criteria was a value of <7.5 mg/dL obtained on-site via a validated point-of-care Hgb measurement device, which necessitated permanent discontinuation of the study medication. None of the participants met the stopping criteria therefore there is no data to present for this outcome measure.
- Percent Change From Baseline in Hepcidin Concentration at Week 24 [Baseline and Week 24]
Baseline is the last pre-dose hepcidin value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the Week 24 value.
- Maximum Observed Change From Baseline in Serum Erythropoietin (EPO) [Baseline to Week 24]
Blood samples for control arm were collected pre-dose for EPO measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for EPO measurement. The maximum observed change from baseline in EPO was recorded for each arm. Baseline value for EPO is the pre-dose value on Day 1. Change from Baseline in EPO was calculated as the individual post-baseline values minus the Baseline value.
- Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF) [Baseline and up to Week 24]
Blood samples for control arm were collected pre-dose for VEGF measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for VEGF measurement. The maximum observed change from baseline in VEGF was recorded for each arm . Baseline value for VEGF is the pre-dose value on Day 1. Change from Baseline in VEGF was calculated as the individual post-baseline values minus the Baseline value.
- Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24 [Weeks 12 to 24]
The number of days a participant's Hgb was within target range was calculated by estimating (using linear interpolation) the number of days within target range between two scheduled Hgb visits. Percentage of time within range for a participant was calculated by dividing the total number of days that Hgb was within range during Weeks 12 to 24 by the total number of days the participant remained on treatment during Weeks 12 to 24. Similary, percent of time above and below Hgb target range was calculated. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL.
- Change From Baseline in Ferritin Concentration at Week 24 [Baseline and Week 24]
Baseline is the last pre-dose ferritin value. Change was calculated by subtracting the Baseline value from the Week 24 value.
- Change From Baseline in Transferrin Concentration at Week 24 [Baseline and Week 24]
Baseline is the last pre-dose transferrin value. Change from Baseline in transferrin was calculated by subtracting the Baseline value from the Week 24 value.
- Percent Change From Baseline in Transferrin Saturation at Week 24 [Baseline and Week 24]
Transferrin saturation is measured as a percentage; it is a ratio of serum iron and total iron-binding capacity. Baseline is the last pre-dose transferrin saturation value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the post-dose value.
- Change From Baseline in Total Iron at Week 24 [Baseline and Week 24]
Baseline is the last pre-dose total iron value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value.
- Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24 [Baseline and Week 24]
TIBC measures the blood's capacity to bind iron with transferrin. Baseline is the last pre-dose TIBC value. Change from Baseline in TIBC was calculated by subtracting the Baseline value from the Week 24 value.
- Change From Baseline in Reticulocyte Hemoglobin (CHr) at Week 24 [Baseline and Week 24]
Reticulocytes are slightly immature red blood cells. Reticulocyte Hgb content is used to differentiate iron deficiency from other causes of anemia. Baseline is the last pre-dose CHr value. Change from Baseline in reticulocyte Hgb was calculated by subtracting the Baseline value from the post-dose value.
- Change From Baseline in Hematocrit at Week 24 [Baseline and Week 24]
Baseline is the last pre-dose hematocrit value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value.
- Change From Baseline in Red Blood Cell Count at Week 24 [Baseline and Week 24]
Baseline is the last pre-dose red blood cell count. Change from Baseline in red blood cell count was calculated by subtracting the Baseline count from the post-dose count.
- Change From Baseline in Reticulocyte Cell Count at Week 24 [Baseline and Week 24]
Reticulocyte count is a blood test that measures the percentage of reticulocytes in the blood. Reticulocytes are slightly immature red blood cells. Baseline is the last pre-dose red reticulocyte count. Change from Baseline in reticulocyte cell count was calculated by subtracting the Baseline count from the Week 24 count.
- Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint [Day 1 (pre-dose), Week (Wk) 4 (6-12 hour, 7-13 hour, 8-14 hour, 9-15 hour post-dose), and Wk 20 (pre-dose, 1 hour, 2 hour, 3 hour post-dose)]
Blood samples were collected for individual plasma GSK1278863 and metabolite (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531401, and GSK2531403) concentration measurement on Day 1 (pre-dose), Wk 4 (6-12 hour, 7-13 hour, 8-14 hour, 9-15 hour post-dose), and Wk 20 (pre-dose, 1 hour, 2 hour, 3 hour post-dose). Participants available in each arm at the specified time points have been presented.
- Mean Number of Dose Adjustments up to 24 Weeks [From Week 4 up to 24 Weeks]
After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system.
- Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency [From week 4 up to 24 weeks]
After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system. Frequency is presented as the number of participants with dose adjustment(s) once, twice, thrice, four times, or five times.
- Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20 [From Week 4 up to Week 20]
After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system. The number of participants with an adjustment are presented at the timings at which adjustments were done.
- Mean Total Cumulative Dose of GSK1278863 up to 24 Weeks [Up to 24 Weeks]
The starting dose was kept constant for the first 4 Weeks after randomization. Later, the need to adjust the dose of GSK1288863 was evaluated at every scheduled visit according to a pre-specified algorithm, to achieve and maintain hemoglobin within the specified target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL.
- Mean Final Dose of GSK1278863 up to 24 Weeks [Up to 24 Weeks]
The starting dose was kept constant for the first 4 Weeks after randomization. Later, the need to adjust the dose of GSK1288863 was evaluated at every scheduled visit according to a pre-specified algorithm, to achieve and maintain hemoglobin within the specified target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL.
- Number of Hemoglobin (Hgb) Excursions [Up to 24 Weeks.]
A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter. Hgb cycle is calculated as two consecutive Hgb excursions in different directions.
- Number of Hemoglobin (Hgb) Cycles up to 24 Weeks [Up to 24 Weeks]
A Hgb cycle is calculated as two consecutive Hgb excursions in different directions. A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter.
- Number of Dose Cycles up to 24 Weeks [Up to 24 weeks]
A dose cycle is a series of three directional dose changes (that is, increase, decrease, increase; or decrease, increase, decrease).
- Number of Participants With at Least One Hemoglobin (Hgb) Excursion up to 24 Weeks. [Up to 24 weeks]
A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter.
- Number of Participants With at Least One Hemoglobin (Hgb) Cycle up to 24 Weeks [Up to 24 weeks]
A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter. A Hgb cycle is two consecutive Hgb excursions in different directions.
- Number of Participants With at Least One Dose Cycle up to 24 Weeks [Up to 24 weeks]
A dose cycle is a series of three directional dose changes (that is, increase, decrease, increase; or decrease, increase, decrease). participants
- Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline [From Day 1 up to Week 28]
Participants receiving additional therapies of blood transfusions, intravenous (IV) iron or rhEPO any time Post Baseline were analyzed. RhEPO was not applicable for the control arms since it was a planned therapy in those arms, hence presented as NA. (EudraCT only: A value of 99999 is used where no data is available or NA.)
- Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit [From Week 4 up to Week 24]
Number of Weeks dose was withheld because hemoglobin exceed the upper limit is presented as the number of participants with withheld dose during the time periods categorized by Weeks.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age: >=18 years of age. (Week -4 verification only)
-
Gender: Female and male subjects. (Week -4 verification only) Females: If of childbearing potential, 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, hysterectomy, or oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. 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.
-
Corrected QT interval (QTc): Bazett's Correction of QT Interval (QTcB) <470 milliseconds (msec) or QTcB <480 msec in subjects with bundle branch block. There is no QTc criterion for subjects with a predominantly paced rhythm.
-
CKD stage: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3/4/5 defined by electronic estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
-
Hgb: Group 1 (rhEPO naïve): Baseline Hgb of 8.0-11.0 g/dL (inclusive) (USA sites only: 8.0-10.0 g/dL, inclusive); Group 2 (rhEPO users): Baseline Hgb of 9.0-11.5 g/dL (inclusive) (USA sites only: 9.0-10.5, inclusive).
-
Stable rhEPO dose for rhEPO users: Group 2 subjects must be using the same rhEPO (epoetins or their biosimilars, or darbepoetin) with total weekly doses that varied by no more than 50% during the 4 weeks prior to Week -4. At Day 1 (randomization), confirm that total weekly doses varied by no more than 50% during the screening period.
-
Oral iron therapy: If on oral iron, then doses must not be changed for the 4 weeks prior to Week -4, during the screening phase, and through the first 4 weeks after Randomization.
Exclusion Criteria:
-
Dialysis: On dialysis or planning to initiate dialysis during the study.
-
Renal transplant: Pre-emptive or scheduled renal transplant.
-
High rhEPO dose: An epoetin dose of >=360 IU/kg/week intravenous (IV) or >=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 microgram per kilogram per week (mcg/kg/week) IV or SC within the prior 8 weeks through Day 1 (randomization).
-
Use of methoxy polyethylene glycol epoetin beta within the prior 8 weeks through Day 1 (randomization).
-
IV iron therapy: Use of IV iron for 4 weeks prior to Screening Week -4, during the screening phase, and through the first 4 weeks after Randomization
-
Vitamin B12: Below the lower limit of the reference range (may rescreen in a minimum of 8 weeks).
-
Folate: <2.0 nanogram per millilitre (ng/mL) (<4.5 nanomoles per liter [nmol/L]) (may rescreen in a minimum of 4 weeks).
-
Ferritin: <40 ng/mL (<40 mcg/L).
-
Transferrin saturation (TSAT): Below the lower limit of the reference range
-
Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to Screening through Day 1 (randomization).
-
Stroke or transient ischemic attack: Within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
-
Heart failure: Class III/IV heart failure as defined by the New York Heart Association (NYHA) functional classification system diagnosed prior to Week -4 Screening through Day 1 (randomization), symptomatic right heart failure diagnosed prior to Week -4 Screening through Day 1 (randomization).
-
Uncontrolled hypertension: Defined as diastolic blood pressure (DBP) >100 mmHg or systolic blood pressure (SBP) >170 mmHg at Week -4 and reconfirmed at Day 1.
-
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), except vascular access thrombosis within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
-
Ophthalmology disease: Meeting any ophthalmologic-related exclusion criteria determined at the Screening ophthalmology exam.
-
Inflammatory disease: Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) diagnosed prior to Week -4 Screening through Day 1 (randomization).
-
Hematological disease: Any hematological disease including those affecting platelets, white or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia and thalassemia), coagulation disorders (e.g., antiphospholipid syndrome, Protein C or S deficiency), or any other cause of anemia other than renal disease diagnosed prior to Week -4 Screening through Day 1 (randomization).
-
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 [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.
-
Major surgery: Major surgery (excluding vascular access surgery) within the prior 8 weeks, during the Week -4 Screening phase or planned during the study.
-
Transfusion: Blood transfusion within the prior 8 weeks, during the Week -4 Screening phase or an anticipated need for blood transfusion during the study.
-
Gastrointestinal (GI) Bleeding: Evidence of actively bleeding peptic, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
-
Acute infection: Clinical evidence of acute infection or history of infection requiring IV antibiotic therapy within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
-
Malignancy: Subjects with a history of malignancy within the prior 5 years, who receiving treatment for cancer, or who have 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 prior to Week -4 Screening through Day 1 (randomization).
-
Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product (see GSK1278863 IB for list of excipients and rhEPO (refer to local product labelling for details).
-
Drugs and supplements: Use of any prescription or non-prescription drugs or dietary supplements that are prohibited from Week -4 Screening until the Follow-up Visit.
-
Prior investigational product exposure: The Subject has participated in a clinical trial and has received an experimental investigational product within the prior 30 days from Week -4 Screening through Day 1 (randomization).
-
Other Conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the Investigator considers would put the subject at unacceptable risk.
-
Patient participation: Unwillingness or inability of the subject to follow the procedures or lifestyle or dietary restrictions outlined in the protocol.
-
Pregnancy or Lactation: Pregnant females as determined by positive urine human chorionic gonadotropin (hCG) test OR women who are lactating at Week -4 Screening or during the trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Peoria | Arizona | United States | 85381 |
| 2 | GSK Investigational Site | Azusa | California | United States | 91702 |
| 3 | GSK Investigational Site | La Mesa | California | United States | 91942 |
| 4 | GSK Investigational Site | Laguna Hills | California | United States | 92653 |
| 5 | GSK Investigational Site | Los Angeles | California | United States | 90022 |
| 6 | GSK Investigational Site | Los Angeles | California | United States | 90025 |
| 7 | GSK Investigational Site | San Diego | California | United States | 92103 |
| 8 | GSK Investigational Site | San Dimas | California | United States | 91773 |
| 9 | GSK Investigational Site | West Hills | California | United States | 91307 |
| 10 | GSK Investigational Site | Lauderdale Lakes | Florida | United States | 33313 |
| 11 | GSK Investigational Site | Miami | Florida | United States | 33150 |
| 12 | GSK Investigational Site | Pembroke Pines | Florida | United States | 33028 |
| 13 | GSK Investigational Site | Macon | Georgia | United States | 31217 |
| 14 | GSK Investigational Site | Savannah | Georgia | United States | 31406 |
| 15 | GSK Investigational Site | Evergreen Park | Illinois | United States | 60805 |
| 16 | GSK Investigational Site | Shreveport | Louisiana | United States | 71101 |
| 17 | GSK Investigational Site | Farmington | Missouri | United States | 63640 |
| 18 | GSK Investigational Site | Charlotte | North Carolina | United States | |
| 19 | GSK Investigational Site | Bethlehem | Pennsylvania | United States | 18017 |
| 20 | GSK Investigational Site | Uniontown | Pennsylvania | United States | 15401 |
| 21 | GSK Investigational Site | Knoxville | Tennessee | United States | 37923 |
| 22 | GSK Investigational Site | Corsicana | Texas | United States | 75110 |
| 23 | GSK Investigational Site | San Antonio | Texas | United States | 78229 |
| 24 | GSK Investigational Site | Temple | Texas | United States | 76508 |
| 25 | GSK Investigational Site | Salt Lake City | Utah | United States | 84112 |
| 26 | GSK Investigational Site | Liverpool | New South Wales | Australia | 2170 |
| 27 | GSK Investigational Site | Westmead | New South Wales | Australia | 2145 |
| 28 | GSK Investigational Site | Adelaide | South Australia | Australia | 5000 |
| 29 | GSK Investigational Site | Nedlands | Western Australia | Australia | 6009 |
| 30 | GSK Investigational Site | Edmonton | Alberta | Canada | T6G 2B7 |
| 31 | GSK Investigational Site | Brampton | Ontario | Canada | L6T 0G1 |
| 32 | GSK Investigational Site | Kitchener | Ontario | Canada | N2G 1E8 |
| 33 | GSK Investigational Site | London | Ontario | Canada | N6A 5A5 |
| 34 | GSK Investigational Site | Mississauga | Ontario | Canada | L5M 2V8 |
| 35 | GSK Investigational Site | Sudbury | Ontario | Canada | P3E 5J1 |
| 36 | GSK Investigational Site | Montreal | Quebec | Canada | H1T 2M4 |
| 37 | GSK Investigational Site | Pointe-Claire | Quebec | Canada | H9R 4S3 |
| 38 | GSK Investigational Site | Cheb | Czechia | 350 02 | |
| 39 | GSK Investigational Site | Liberec | Czechia | 460 63 | |
| 40 | GSK Investigational Site | Louny | Czechia | 440 01 | |
| 41 | GSK Investigational Site | Marianske Lazne | Czechia | 353 01 | |
| 42 | GSK Investigational Site | Most | Czechia | 434 64 | |
| 43 | GSK Investigational Site | Praha 10 | Czechia | 100 34 | |
| 44 | GSK Investigational Site | Praha 2 | Czechia | 128 08 | |
| 45 | GSK Investigational Site | Praha 4 | Czechia | 142 00 | |
| 46 | GSK Investigational Site | Sokolov | Czechia | 356 01 | |
| 47 | GSK Investigational Site | Odense C | Denmark | 5000 | |
| 48 | GSK Investigational Site | Roskilde | Denmark | DK-4000 | |
| 49 | GSK Investigational Site | Amiens cedex 1 | France | 80054 | |
| 50 | GSK Investigational Site | Bordeaux | France | 33000 | |
| 51 | GSK Investigational Site | Caen Cedex 9 | France | 14033 | |
| 52 | GSK Investigational Site | Créteil Cedex | France | 94010 | |
| 53 | GSK Investigational Site | Lyon Cedex 03 | France | 69437 | |
| 54 | GSK Investigational Site | Paris Cedex 15 | France | 75743 | |
| 55 | GSK Investigational Site | Sainte Foy-Lès-Lyon | France | 69110 | |
| 56 | GSK Investigational Site | Mannheim | Baden-Wuerttemberg | Germany | 68167 |
| 57 | GSK Investigational Site | Ulm | Baden-Wuerttemberg | Germany | 89081 |
| 58 | GSK Investigational Site | Muenchen | Bayern | Germany | 81675 |
| 59 | GSK Investigational Site | Demmin | Mecklenburg-Vorpommern | Germany | 17109 |
| 60 | GSK Investigational Site | Duesseldorf | Nordrhein-Westfalen | Germany | 40210 |
| 61 | GSK Investigational Site | Leipzig | Sachsen | Germany | 04129 |
| 62 | GSK Investigational Site | Berlin | Germany | 12053 | |
| 63 | GSK Investigational Site | Hamburg | Germany | 22297 | |
| 64 | GSK Investigational Site | Budapest | Hungary | 1036 | |
| 65 | GSK Investigational Site | Budapest | Hungary | 1097 | |
| 66 | GSK Investigational Site | Budapest | Hungary | 1115 | |
| 67 | GSK Investigational Site | Budapest | Hungary | 1135 | |
| 68 | GSK Investigational Site | Székesfehérvár | Hungary | 8000 | |
| 69 | GSK Investigational Site | Aichi | Japan | 455-8530 | |
| 70 | GSK Investigational Site | Gifu | Japan | 500-8717 | |
| 71 | GSK Investigational Site | Gunma | Japan | 370-0001 | |
| 72 | GSK Investigational Site | Ibaraki | Japan | 302-0014 | |
| 73 | GSK Investigational Site | Ibaraki | Japan | 302-0022 | |
| 74 | GSK Investigational Site | Kanagawa | Japan | 210-0852 | |
| 75 | GSK Investigational Site | Kyoto | Japan | 604-8845 | |
| 76 | GSK Investigational Site | Nagano | Japan | 388-8004 | |
| 77 | GSK Investigational Site | Osaka | Japan | 558-8558 | |
| 78 | GSK Investigational Site | Shiga | Japan | 523-0082 | |
| 79 | GSK Investigational Site | Anyang-Si Gyeonggi-do | Korea, Republic of | 431-070 | |
| 80 | GSK Investigational Site | Daegu | Korea, Republic of | 700-721 | |
| 81 | GSK Investigational Site | Daejeon | Korea, Republic of | 301-721 | |
| 82 | GSK Investigational Site | Gwangju | Korea, Republic of | 501-757 | |
| 83 | GSK Investigational Site | Krakow | Poland | 31-501 | |
| 84 | GSK Investigational Site | Lublin | Poland | 20-081 | |
| 85 | GSK Investigational Site | Tarnow | Poland | 33-100 | |
| 86 | GSK Investigational Site | Warszawa | Poland | 02-507 | |
| 87 | GSK Investigational Site | Zabrze | Poland | 41-800 | |
| 88 | GSK Investigational Site | Izhevsk | Russian Federation | 426063 | |
| 89 | GSK Investigational Site | Kaluga | Russian Federation | 248007 | |
| 90 | GSK Investigational Site | Khantymansiysk | Russian Federation | 628012 | |
| 91 | GSK Investigational Site | Krasnodar | Russian Federation | 350029 | |
| 92 | GSK Investigational Site | Krasnoyarsk | Russian Federation | 660062 | |
| 93 | GSK Investigational Site | Moscow | Russian Federation | 119121 | |
| 94 | GSK Investigational Site | Moscow | Russian Federation | 125101 | |
| 95 | GSK Investigational Site | St-Petersburg | Russian Federation | 197110 | |
| 96 | GSK Investigational Site | Ulyanovsk | Russian Federation | 432063 | |
| 97 | GSK Investigational Site | Yaroslavl | Russian Federation | 150062 | |
| 98 | GSK Investigational Site | Alcala de Henares | Spain | 28805 | |
| 99 | GSK Investigational Site | Badalona | Spain | 08916 | |
| 100 | GSK Investigational Site | Barcelona | Spain | 08011 | |
| 101 | GSK Investigational Site | Barcelona | Spain | 08035 | |
| 102 | GSK Investigational Site | Barcelona | Spain | 08907 | |
| 103 | GSK Investigational Site | Cordoba | Spain | 14004 | |
| 104 | GSK Investigational Site | Granada | Spain | 18014 | |
| 105 | GSK Investigational Site | Madrid | Spain | 28041 | |
| 106 | GSK Investigational Site | Madrid | Spain | 28224 | |
| 107 | GSK Investigational Site | San Sebastian de los Reyes | Spain | 28702 | |
| 108 | GSK Investigational Site | Santander | Spain | 39008 | |
| 109 | GSK Investigational Site | Santiago de Compostela | Spain | 15706 | |
| 110 | GSK Investigational Site | Göteborg | Sweden | SE-413 45 | |
| 111 | GSK Investigational Site | Karlstad | Sweden | SE-651 85 | |
| 112 | GSK Investigational Site | Stockholm | Sweden | SE-141 86 | |
| 113 | GSK Investigational Site | Uppsala | Sweden | SE-751 85 | |
| 114 | GSK Investigational Site | Örebro | Sweden | SE-701 85 | |
| 115 | GSK Investigational Site | Chelmsford | United Kingdom | CM1 7ET | |
| 116 | GSK Investigational Site | Dorchester | United Kingdom | DT1 2JY | |
| 117 | GSK Investigational Site | Dundee | United Kingdom | DD1 9SY | |
| 118 | GSK Investigational Site | Hull | United Kingdom | HU3 2JZ | |
| 119 | GSK Investigational Site | Leeds | United Kingdom | LS9 7TF | |
| 120 | GSK Investigational Site | London | United Kingdom | E1 1BB | |
| 121 | GSK Investigational Site | London | United Kingdom | NW3 2QG | |
| 122 | GSK Investigational Site | Manchester | United Kingdom | M13 9WL | |
| 123 | GSK Investigational Site | Oxford | United Kingdom | OX3 7LE |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01977573
Other Study ID Numbers:
- 113747
First Posted:
Nov 6, 2013
Last Update Posted:
Oct 12, 2018
Last Verified:
Sep 1, 2018
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Two groups of participants(par.) were enrolled in this study. Group 1 consisted of recombinant human erythropoietin(rhEPO)-naive par. whereas Group 2 consisted of rhEPO users. |
|---|---|
| Pre-assignment Detail | Post screening, eligible par. were randomized to receive either GSK1278863 once a day (QD) or to the Control arm in a 3:1 fashion in Group 1 and 1:1 fashion in Group 2. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Period Title: Overall Study | ||||
| STARTED | 136 | 44 | 36 | 36 |
| COMPLETED | 116 | 41 | 32 | 33 |
| NOT COMPLETED | 20 | 3 | 4 | 3 |
Baseline Characteristics
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control | Total |
|---|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. | Total of all reporting groups |
| Overall Participants | 123 | 43 | 33 | 36 | 235 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
67.6
(12.21)
|
64.3
(14.22)
|
62.0
(14.06)
|
66.7
(12.89)
|
66.1
(13.04)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
75
61%
|
23
53.5%
|
17
51.5%
|
23
63.9%
|
138
58.7%
|
| Male |
48
39%
|
20
46.5%
|
16
48.5%
|
13
36.1%
|
97
41.3%
|
| Race/Ethnicity, Customized (Number) [Number] | |||||
| African American/African Heritage |
14
11.4%
|
2
4.7%
|
2
6.1%
|
4
11.1%
|
22
9.4%
|
| Central/South Asian Heritage |
0
0%
|
0
0%
|
0
0%
|
1
2.8%
|
1
0.4%
|
| Japanese/East Asian/South East Asian Heritage |
28
22.8%
|
11
25.6%
|
9
27.3%
|
12
33.3%
|
60
25.5%
|
| White |
81
65.9%
|
30
69.8%
|
22
66.7%
|
19
52.8%
|
152
64.7%
|
Outcome Measures
| Title | Summary of Hemoglobin (Hgb) Concentration at Week 24 |
|---|---|
| Description | The original Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-10.0 g/dL (8.0-10.0 g/dL USA site only) and for Group 2- rhEPO users with a stable baseline Hgb of 9.0-10.5 g/dL (9.0-10.5 g/dL USA site only); the Hgb target range was 9.0 to 10.5 g/dL (9.0-10.5 g/dL USA site only). The study amended Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-11.0 g/dL and Group 2- rhEPO users with a stable baseline Hgb of 9.0-11.5 g/dL; Hgb target range - 10.0 to 11.5 g/dL. Data are presented for those participants following the original criteria ("Original") and those following the amended ("Amended") criteria. The primary objective was to characterize the ability of GSK1278863 to achieve mean Hgb response within the target range. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT): The ITT population consisted of all randomized participants who received at least one dose of study drug, had a Baseline and at least one corresponding on-treatment assessment. Only participants who were available at the indicated time point were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 123 | 43 | 33 | 36 |
| Original n=45,15,19,13 |
10.20
(0.906)
|
10.64
(0.664)
|
10.03
(0.522)
|
10.66
(0.620)
|
| Amended n=61,21,11,17 |
10.96
(1.044)
|
11.05
(1.144)
|
10.42
(0.827)
|
10.86
(1.182)
|
| Title | Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24 |
|---|---|
| Description | Target range is defined as: Original Hgb Criteria of 9.0 to 10.5 gram/deciliter (g/dL), and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants who were available at the indicated time point were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 106 | 36 | 30 | 30 |
| Number [participants] |
78
63.4%
|
20
46.5%
|
22
66.7%
|
19
52.8%
|
| Title | Number of Participants Reaching Pre-defined Hgb Stopping Criteria |
|---|---|
| Description | The Hgb stopping criteria was a value of <7.5 mg/dL obtained on-site via a validated point-of-care Hgb measurement device, which necessitated permanent discontinuation of the study medication. None of the participants met the stopping criteria therefore there is no data to present for this outcome measure. |
| Time Frame | Over a period of 24 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 136 | 44 | 36 | 36 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Percent Change From Baseline in Hepcidin Concentration at Week 24 |
|---|---|
| Description | Baseline is the last pre-dose hepcidin value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the Week 24 value. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) population consisted all randomized participants who received at least one dose of study drug, had a Baseline and at least one corresponding on-treatment assessment. Only participants with available hepcidin values at Baseline and Week 24 were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 106 | 35 | 30 | 29 |
| Geometric Mean (95% Confidence Interval) [percent change in Hepcidin] |
-19.27
|
6.67
|
-9.87
|
-17.12
|
| Title | Maximum Observed Change From Baseline in Serum Erythropoietin (EPO) |
|---|---|
| Description | Blood samples for control arm were collected pre-dose for EPO measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for EPO measurement. The maximum observed change from baseline in EPO was recorded for each arm. Baseline value for EPO is the pre-dose value on Day 1. Change from Baseline in EPO was calculated as the individual post-baseline values minus the Baseline value. |
| Time Frame | Baseline to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants having a Baseline EPO measurement and at least one post-baseline EPO measurement were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 123 | 42 | 33 | 36 |
| Mean (Standard Deviation) [International Units per liter] |
7.27
(12.744)
|
27.05
(94.999)
|
3.69
(20.554)
|
25.85
(38.890)
|
| Title | Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF) |
|---|---|
| Description | Blood samples for control arm were collected pre-dose for VEGF measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for VEGF measurement. The maximum observed change from baseline in VEGF was recorded for each arm . Baseline value for VEGF is the pre-dose value on Day 1. Change from Baseline in VEGF was calculated as the individual post-baseline values minus the Baseline value. |
| Time Frame | Baseline and up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with data available at Baseline and a maximum observed change were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 123 | 42 | 33 | 36 |
| Geometric Mean (95% Confidence Interval) [percent change in VEGF concentration] |
76.36
|
26.84
|
49.99
|
40.85
|
| Title | Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24 |
|---|---|
| Description | The number of days a participant's Hgb was within target range was calculated by estimating (using linear interpolation) the number of days within target range between two scheduled Hgb visits. Percentage of time within range for a participant was calculated by dividing the total number of days that Hgb was within range during Weeks 12 to 24 by the total number of days the participant remained on treatment during Weeks 12 to 24. Similary, percent of time above and below Hgb target range was calculated. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. |
| Time Frame | Weeks 12 to 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with data available at specific time points were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 112 | 38 | 30 | 32 |
| Percentage of time within target range |
68.99
(34.612)
|
51.01
(41.403)
|
75.06
(32.485)
|
61.29
(43.352)
|
| Percentage of time above target range |
22.84
(33.825)
|
45.10
(42.579)
|
17.96
(28.809)
|
31.10
(41.683)
|
| Percentage of time below target range |
8.17
(20.301)
|
3.89
(16.175)
|
6.98
(21.118)
|
7.61
(25.113)
|
| Title | Change From Baseline in Ferritin Concentration at Week 24 |
|---|---|
| Description | Baseline is the last pre-dose ferritin value. Change was calculated by subtracting the Baseline value from the Week 24 value. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with data available at specific time point were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 108 | 36 | 30 | 30 |
| Mean (Standard Deviation) [micrograms per liter] |
-30.8
(110.50)
|
-2.4
(77.06)
|
-63.4
(141.93)
|
-20.4
(63.38)
|
| Title | Change From Baseline in Transferrin Concentration at Week 24 |
|---|---|
| Description | Baseline is the last pre-dose transferrin value. Change from Baseline in transferrin was calculated by subtracting the Baseline value from the Week 24 value. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with data available at specific time point were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 107 | 36 | 30 | 30 |
| Mean (Standard Deviation) [grams per liter] |
0.077
(0.3577)
|
-0.008
(0.2694)
|
0.171
(0.4124)
|
0.018
(0.2395)
|
| Title | Percent Change From Baseline in Transferrin Saturation at Week 24 |
|---|---|
| Description | Transferrin saturation is measured as a percentage; it is a ratio of serum iron and total iron-binding capacity. Baseline is the last pre-dose transferrin saturation value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the post-dose value. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with data available at specific time point were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 106 | 35 | 30 | 30 |
| Geometric Mean (95% Confidence Interval) [percent change] |
-1.1
|
12.3
|
-15.7
|
11.4
|
| Title | Change From Baseline in Total Iron at Week 24 |
|---|---|
| Description | Baseline is the last pre-dose total iron value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with available total iron values at Baseline and Week 24 were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 107 | 36 | 30 | 30 |
| Mean (Standard Deviation) [micromoles per liter] |
1.0
(5.01)
|
2.5
(5.98)
|
-1.8
(5.54)
|
0.7
(8.36)
|
| Title | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24 |
|---|---|
| Description | TIBC measures the blood's capacity to bind iron with transferrin. Baseline is the last pre-dose TIBC value. Change from Baseline in TIBC was calculated by subtracting the Baseline value from the Week 24 value. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with data available at specific timepoint were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 106 | 35 | 30 | 30 |
| Mean (Standard Deviation) [micromoles per liter] |
3.2
(6.46)
|
0.1
(5.17)
|
3.0
(9.44)
|
-1.0
(6.69)
|
| Title | Change From Baseline in Reticulocyte Hemoglobin (CHr) at Week 24 |
|---|---|
| Description | Reticulocytes are slightly immature red blood cells. Reticulocyte Hgb content is used to differentiate iron deficiency from other causes of anemia. Baseline is the last pre-dose CHr value. Change from Baseline in reticulocyte Hgb was calculated by subtracting the Baseline value from the post-dose value. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with data available at specific time point were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 108 | 35 | 30 | 30 |
| Mean (Standard Deviation) [picogram] |
-0.19
(1.109)
|
-0.33
(1.085)
|
-0.32
(0.864)
|
-0.19
(1.546)
|
| Title | Change From Baseline in Hematocrit at Week 24 |
|---|---|
| Description | Baseline is the last pre-dose hematocrit value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with data available at specific timepoint were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 111 | 36 | 30 | 30 |
| Mean (Standard Deviation) [percentage change in Fraction of 1] |
2.64
(3.389)
|
3.13
(3.245)
|
-0.66
(3.074)
|
2.09
(3.243)
|
| Title | Change From Baseline in Red Blood Cell Count at Week 24 |
|---|---|
| Description | Baseline is the last pre-dose red blood cell count. Change from Baseline in red blood cell count was calculated by subtracting the Baseline count from the post-dose count. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with data available at specific time point were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 111 | 36 | 30 | 30 |
| Mean (Standard Deviation) [10^12 cells per liter] |
0.28
(0.377)
|
0.34
(0.365)
|
-0.08
(0.312)
|
0.22
(0.318)
|
| Title | Change From Baseline in Reticulocyte Cell Count at Week 24 |
|---|---|
| Description | Reticulocyte count is a blood test that measures the percentage of reticulocytes in the blood. Reticulocytes are slightly immature red blood cells. Baseline is the last pre-dose red reticulocyte count. Change from Baseline in reticulocyte cell count was calculated by subtracting the Baseline count from the Week 24 count. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only participants with data available at specific timepoint were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 111 | 36 | 30 | 31 |
| Mean (Standard Deviation) [percentage of reticulocytes] |
-0.02
(0.551)
|
-0.12
(0.648)
|
0.27
(0.892)
|
-0.09
(0.755)
|
| Title | Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint |
|---|---|
| Description | Blood samples were collected for individual plasma GSK1278863 and metabolite (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531401, and GSK2531403) concentration measurement on Day 1 (pre-dose), Wk 4 (6-12 hour, 7-13 hour, 8-14 hour, 9-15 hour post-dose), and Wk 20 (pre-dose, 1 hour, 2 hour, 3 hour post-dose). Participants available in each arm at the specified time points have been presented. |
| Time Frame | Day 1 (pre-dose), Week (Wk) 4 (6-12 hour, 7-13 hour, 8-14 hour, 9-15 hour post-dose), and Wk 20 (pre-dose, 1 hour, 2 hour, 3 hour post-dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) population: All participants from whom a PK sample was obtained and analyzed. This population did not include participants from the control groups. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-User GSK1278863 |
|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). |
| Measure Participants | 134 | 35 |
| GSK1278863, Day 1, Pre-Dose, n=128, 35 |
0.0
(0.00)
|
0.0
(0.00)
|
| GSK1278863, Wk 4, 6-12 hour Post-Dose, n=116, 31 |
2.0
(5.18)
|
1.1
(1.69)
|
| GSK1278863, Wk 4, 7-13 hour Post-Dose, n=117, 31 |
2.3
(7.06)
|
0.8
(1.22)
|
| GSK1278863, Wk 4, 8-14 hour Post-Dose, n=116, 31 |
1.6
(4.93)
|
1.6
(5.49)
|
| GSK1278863, Wk 4, 9-15 hour Post-Dose, n=116, 31 |
1.4
(4.52)
|
1.6
(4.60)
|
| GSK1278863, Wk 20, Pre-Dose, n=111, 29 |
0.6
(3.07)
|
0.3
(0.92)
|
| GSK1278863, Wk 20, 1 hour Post-Dose, n=110, 28 |
22.8
(35.93)
|
19.8
(19.66)
|
| GSK1278863, Wk 20, 2 hour Post-Dose, n=109, 29 |
17.0
(28.57)
|
19.4
(21.92)
|
| GSK1278863, Wk 20, 3 hour Post-Dose, n=109, 29 |
11.6
(19.56)
|
13.9
(19.12)
|
| GSK2391220, Day 1, Pre-Dose, n=128, 35 |
0.0
(0.00)
|
0.0
(0.00)
|
| GSK2391220, Wk 4, 6-12 hour Post-Dose, n=116, 31 |
3.2
(5.21)
|
3.7
(2.89)
|
| GSK2391220, Wk 4, 7-13 hour Post-Dose, n=117, 31 |
3.1
(5.67)
|
3.2
(2.43)
|
| GSK2391220, Wk 4, 8-14 hour Post-Dose, n=116, 31 |
2.8
(5.01)
|
2.9
(2.54)
|
| GSK2391220, Wk 4, 9-15 hour Post-Dose, n=116, 31 |
2.6
(4.89)
|
3.1
(2.76)
|
| GSK2391220, Wk 20, Pre-Dose, n=111, 29 |
1.0
(2.06)
|
0.8
(0.98)
|
| GSK2391220, Wk 20, 1 hour Post-Dose, n=110, 28 |
2.1
(3.52)
|
1.6
(1.39)
|
| GSK2391220, Wk 20, 2 hour Post-Dose, n=109, 29 |
3.8
(5.08)
|
3.7
(2.98)
|
| GSK2391220, Wk 20, 3 hour Post-Dose, n=109, 29 |
4.5
(5.43)
|
4.7
(3.53)
|
| GSK2487818, Day 1, Pre-Dose, n=128, 35 |
0.0
(0.00)
|
0.0
(0.00)
|
| GSK2487818, Wk 4, 6-12 hour Post-Dose, n=116, 31 |
1.2
(3.87)
|
1.0
(0.96)
|
| GSK2487818, Wk 4, 7-13 hour Post-Dose, n=116, 31 |
1.1
(4.11)
|
0.7
(0.70)
|
| GSK2487818, Wk 4, 8-14 hour Post-Dose, n=116, 31 |
1.0
(4.48)
|
0.6
(0.66)
|
| GSK2487818, Wk 4, 9-15 hour Post-Dose, n=116, 31 |
0.9
(4.09)
|
0.8
(1.16)
|
| GSK2487818, Wk 20, Pre-Dose, n=111, 29 |
0.2
(0.56)
|
0.1
(0.31)
|
| GSK2487818, Wk 20, 1 hour Post-Dose, n=110, 28 |
1.4
(3.07)
|
1.0
(1.09)
|
| GSK2487818, Wk 20, 2 hour Post-Dose, n=109, 29 |
2.8
(4.28)
|
2.7
(2.21)
|
| GSK2487818, Wk 20, 3 hour Post-Dose, n=109, 29 |
3.1
(4.07)
|
3.1
(2.56)
|
| GSK2506102, Day 1, Pre-Dose, n=128, 35 |
0.0
(0.00)
|
0.0
(0.00)
|
| GSK2506102, Wk 4, 6-12 hour Post-Dose, n=116, 31 |
1.0
(1.30)
|
1.2
(0.65)
|
| GSK2506102, Wk 4, 7-13 hour Post-Dose, n=117, 31 |
1.0
(1.51)
|
1.1
(0.61)
|
| GSK2506102, Wk 4, 8-14 hour Post-Dose, n=116, 31 |
0.9
(1.19)
|
1.0
(0.61)
|
| GSK2506102, Wk 4, 9-15 hour Post-Dose, n=116, 31 |
0.9
(1.29)
|
1.1
(0.69)
|
| GSK2506102, Wk 20, Pre-Dose, n=111, 29 |
0.4
(0.73)
|
0.4
(0.42)
|
| GSK2506102, Wk 20, 1 hour Post-Dose, n=110, 28 |
0.6
(0.88)
|
0.5
(0.40)
|
| GSK2506102, Wk 20, 2 hour Post-Dose, n=109, 29 |
0.9
(1.15)
|
1.0
(0.71)
|
| GSK2506102, Wk 20, 3 hour Post-Dose, n=109, 29 |
1.1
(1.25)
|
1.2
(0.88)
|
| GSK2531398, Day 1, Pre-Dose, n=128, 35 |
0.0
(0.01)
|
0.0
(0.00)
|
| GSK2531398, Wk 4, 6-12 hour Post-Dose, n=116, 31 |
1.3
(2.06)
|
1.4
(1.08)
|
| GSK2531398, Wk 4, 7-13 hour Post-Dose, n=117, 31 |
1.2
(2.50)
|
1.2
(0.99)
|
| GSK2531398, Wk 4, 8-14 hour Post-Dose, n=116, 31 |
1.1
(2.01)
|
1.1
(0.93)
|
| GSK2531398, Wk 4, 9-15 hour Post-Dose, n=116, 31 |
1.0
(2.10)
|
1.2
(1.12)
|
| GSK2531398, Wk 20, Pre-Dose, n=111, 29 |
0.3
(0.87)
|
0.3
(0.38)
|
| GSK2531398, Wk 20, 1 hour Post-Dose, n=110, 28 |
0.8
(1.53)
|
0.6
(0.54)
|
| GSK2531398, Wk 20, 2 hour Post-Dose, n=109, 29 |
1.6
(2.31)
|
1.5
(1.22)
|
| GSK2531398, Wk 20, 3 hour Post-Dose, n=109, 29 |
2.0
(2.42)
|
2.0
(1.57)
|
| GSK2531401, Day 1, Pre-Dose, n=128, 35 |
0.0
(0.00)
|
0.0
(0.00)
|
| GSK2531401, Wk 4, 6-12 hour Post-Dose, n=116, 31 |
2.8
(4.00)
|
4.3
(2.55)
|
| GSK2531401, Wk 4, 7-13 hour Post-Dose, n=117, 31 |
2.7
(3.58)
|
4.0
(2.29)
|
| GSK2531401, Wk 4, 8-14 hour Post-Dose, n=116, 31 |
2.7
(3.74)
|
3.8
(2.31)
|
| GSK2531401, Wk 4, 9-15 hour Post-Dose, n=116, 31 |
2.5
(3.53)
|
3.8
(2.29)
|
| GSK2531401, Wk 20, Pre-Dose, n=111, 29 |
1.3
(2.41)
|
1.4
(1.38)
|
| GSK2531401, Wk 20, 1 hour Post-Dose, n=110, 28 |
1.6
(2.65)
|
1.6
(1.29)
|
| GSK2531401, Wk 20, 2 hour Post-Dose, n=109, 29 |
2.3
(3.14)
|
2.5
(1.85)
|
| GSK2531401, Wk 20, 3 hour Post-Dose, n=109, 29 |
2.8
(3.50)
|
3.2
(2.22)
|
| GSK2531403, Day 1, Pre-Dose, n=128, 35 |
0.0
(0.00)
|
0.0
(0.00)
|
| GSK2531403, Wk 4, 6-12 hour Post-Dose, n=116, 31 |
3.7
(5.43)
|
4.5
(3.14)
|
| GSK2531403, Wk 4, 7-13 hour Post-Dose, n=117, 31 |
3.5
(5.27)
|
3.9
(2.56)
|
| GSK2531403, Wk 4, 8-14 hour Post-Dose, n=116, 31 |
3.4
(5.68)
|
3.7
(2.72)
|
| GSK2531403, Wk 4, 9-15 hour Post-Dose, n=116, 31 |
3.2
(5.42)
|
3.8
(3.01)
|
| GSK2531403, Wk 20, Pre-Dose, n=111, 29 |
1.4
(2.65)
|
1.2
(1.25)
|
| GSK2531403, Wk 20, 1 hour Post-Dose, n=110, 28 |
2.3
(3.69)
|
1.9
(1.38)
|
| GSK2531403, Wk 20, 2 hour Post-Dose, n=109, 29 |
3.9
(5.03)
|
3.8
(2.95)
|
| GSK2531403, Wk 20, 3 hour Post-Dose, n=109, 29 |
4.7
(5.43)
|
4.9
(3.75)
|
| Title | Mean Number of Dose Adjustments up to 24 Weeks |
|---|---|
| Description | After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system. |
| Time Frame | From Week 4 up to 24 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population. Only those participants with at least one dose adjustment of GSK1278863 were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-User GSK1278863 |
|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). |
| Measure Participants | 102 | 26 |
| Mean (Standard Deviation) [number of adjustments] |
1.8
(0.82)
|
1.7
(0.72)
|
| Title | Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency |
|---|---|
| Description | After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system. Frequency is presented as the number of participants with dose adjustment(s) once, twice, thrice, four times, or five times. |
| Time Frame | From week 4 up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population. Only those participants with at least one dose adjustment of GSK1278863 were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-User GSK1278863 |
|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). |
| Measure Participants | 102 | 26 |
| Once |
39
31.7%
|
11
25.6%
|
| Twice |
50
40.7%
|
11
25.6%
|
| Thrice |
8
6.5%
|
4
9.3%
|
| Four times |
4
3.3%
|
0
0%
|
| Five times or more |
1
0.8%
|
0
0%
|
| Title | Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20 |
|---|---|
| Description | After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system. The number of participants with an adjustment are presented at the timings at which adjustments were done. |
| Time Frame | From Week 4 up to Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Only those participants with at least one dose adjustment of GSK1278863 were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-User GSK1278863 |
|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). |
| Measure Participants | 102 | 26 |
| Week 4 |
78
63.4%
|
21
48.8%
|
| Week 8 |
24
19.5%
|
6
14%
|
| Week 12 |
30
24.4%
|
7
16.3%
|
| Week 16 |
30
24.4%
|
6
14%
|
| Week 20 |
22
17.9%
|
5
11.6%
|
| Title | Mean Total Cumulative Dose of GSK1278863 up to 24 Weeks |
|---|---|
| Description | The starting dose was kept constant for the first 4 Weeks after randomization. Later, the need to adjust the dose of GSK1288863 was evaluated at every scheduled visit according to a pre-specified algorithm, to achieve and maintain hemoglobin within the specified target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. |
| Time Frame | Up to 24 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-User GSK1278863 |
|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). |
| Measure Participants | 123 | 33 |
| Mean (Standard Deviation) [milligrams] |
249.75
(186.921)
|
320.42
(214.865)
|
| Title | Mean Final Dose of GSK1278863 up to 24 Weeks |
|---|---|
| Description | The starting dose was kept constant for the first 4 Weeks after randomization. Later, the need to adjust the dose of GSK1288863 was evaluated at every scheduled visit according to a pre-specified algorithm, to achieve and maintain hemoglobin within the specified target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. |
| Time Frame | Up to 24 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-User GSK1278863 |
|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). |
| Measure Participants | 123 | 33 |
| Mean (Standard Deviation) [milligrams per day] |
1.75
(1.809)
|
1.86
(1.692)
|
| Title | Number of Hemoglobin (Hgb) Excursions |
|---|---|
| Description | A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter. Hgb cycle is calculated as two consecutive Hgb excursions in different directions. |
| Time Frame | Up to 24 Weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Completers Population: ITT participants who fully completed study without prematurely discontinuing study drug. Only participants with Hgb excursions were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 23 | 10 | 4 | 8 |
| Number [number of excursions] |
26
|
10
|
4
|
9
|
| Title | Number of Hemoglobin (Hgb) Cycles up to 24 Weeks |
|---|---|
| Description | A Hgb cycle is calculated as two consecutive Hgb excursions in different directions. A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter. |
| Time Frame | Up to 24 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Completers population. Only participants with Hgb cycles were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 3 | 0 | 0 | 0 |
| Number [number of Hgb cycles] |
3
|
| Title | Number of Dose Cycles up to 24 Weeks |
|---|---|
| Description | A dose cycle is a series of three directional dose changes (that is, increase, decrease, increase; or decrease, increase, decrease). |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Completers population. Only participants in the GSK1278863 arms with dose cycles were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-User GSK1278863 |
|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). |
| Measure Participants | 1 | 0 |
| Number [number] |
1
|
| Title | Number of Participants With at Least One Hemoglobin (Hgb) Excursion up to 24 Weeks. |
|---|---|
| Description | A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter. |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Completers population. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 106 | 36 | 30 | 30 |
| Number [participants] |
23
18.7%
|
10
23.3%
|
4
12.1%
|
8
22.2%
|
| Title | Number of Participants With at Least One Hemoglobin (Hgb) Cycle up to 24 Weeks |
|---|---|
| Description | A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter. A Hgb cycle is two consecutive Hgb excursions in different directions. |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Completers population. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 106 | 36 | 30 | 30 |
| Number [participants] |
3
2.4%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With at Least One Dose Cycle up to 24 Weeks |
|---|---|
| Description | A dose cycle is a series of three directional dose changes (that is, increase, decrease, increase; or decrease, increase, decrease). participants |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Completers population. Only participants in the GSK1278863 arms with dose cycles were analyzed. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-User GSK1278863 |
|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). |
| Measure Participants | 106 | 30 |
| Number [participants] |
1
0.8%
|
0
0%
|
| Title | Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline |
|---|---|
| Description | Participants receiving additional therapies of blood transfusions, intravenous (IV) iron or rhEPO any time Post Baseline were analyzed. RhEPO was not applicable for the control arms since it was a planned therapy in those arms, hence presented as NA. (EudraCT only: A value of 99999 is used where no data is available or NA.) |
| Time Frame | From Day 1 up to Week 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control |
|---|---|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. |
| Measure Participants | 123 | 43 | 33 | 36 |
| Blood Transfusions |
3
2.4%
|
1
2.3%
|
1
3%
|
0
0%
|
| IV Iron |
20
16.3%
|
3
7%
|
3
9.1%
|
4
11.1%
|
| Inadvertent rhEPO use |
4
3.3%
|
NA
NaN
|
9
27.3%
|
NA
NaN
|
| Rescue rhEPO |
1
0.8%
|
NA
NaN
|
0
0%
|
NA
NaN
|
| Title | Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit |
|---|---|
| Description | Number of Weeks dose was withheld because hemoglobin exceed the upper limit is presented as the number of participants with withheld dose during the time periods categorized by Weeks. |
| Time Frame | From Week 4 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-User GSK1278863 |
|---|---|---|
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). |
| Measure Participants | 123 | 33 |
| 0 Weeks |
102
82.9%
|
30
69.8%
|
| >0-4 Weeks |
4
3.3%
|
2
4.7%
|
| >4-8 Weeks |
8
6.5%
|
0
0%
|
| >8-12 Weeks |
8
6.5%
|
0
0%
|
| >12 Weeks |
1
0.8%
|
0
0%
|
Adverse Events
| Time Frame | Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment until the follow-up contact (up to 28 weeks). | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AEs and SAEs were collected from participants of the safety population, comprised of all participants who received at least one dose of study drug. | |||||||
| Arm/Group Title | rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control | ||||
| Arm/Group Description | RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28. | RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28. | RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator's opinion] to start rhEPO therapy). | RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28. | ||||
All Cause Mortality |
||||||||
| rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 23/134 (17.2%) | 7/45 (15.6%) | 7/36 (19.4%) | 7/35 (20%) | ||||
| Cardiac disorders | ||||||||
| ANY EVENT | 4/134 (3%) | 1/45 (2.2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| ANGINA PECTORIS | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| ATRIOVENTRICULAR BLOCK COMPLETE | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| CARDIAC FAILURE CONGESTIVE | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| MYOCARDIAL ISCHAEMIA | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| CARDIAC FAILURE | 0/134 (0%) | 1/45 (2.2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Acute myocardial infarction | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Atrial fibrillation | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| ANY EVENT | 1/134 (0.7%) | 0/45 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| GASTRIC ULCER | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| SMALL INTESTINAL OBSTRUCTION | 0/134 (0%) | 0/45 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| RECTAL HAEMORRHAGE | 0/134 (0%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Vomiting | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| General disorders | ||||||||
| ANY EVENT | 0/134 (0%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| CHEST PAIN | 0/134 (0%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Fatigue | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Infections and infestations | ||||||||
| ANY EVENT | 2/134 (1.5%) | 3/45 (6.7%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| PNEUMONIA | 1/134 (0.7%) | 1/45 (2.2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| PYELONEPHRITIS CHRONIC | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| APPENDICITIS | 0/134 (0%) | 1/45 (2.2%) | 0/36 (0%) | 0/35 (0%) | ||||
| CELLULITIS | 0/134 (0%) | 1/45 (2.2%) | 0/36 (0%) | 0/35 (0%) | ||||
| PNEUMONIA PNEUMOCOCCAL | 0/134 (0%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Biliary sepsis | 0/134 (0%) | 0/45 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Bronchitis | 0/134 (0%) | 1/45 (2.2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Gastroenteritis | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Sepsis | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Subcutaneous abscess | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Shunt malfunction | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Investigations | ||||||||
| ANY EVENT | 2/134 (1.5%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| ALANINE AMINOTRANSFERASE INCREASED | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| FALSE POSITIVE INVESTIGATION RESULT | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| ANY EVENT | 2/134 (1.5%) | 1/45 (2.2%) | 0/36 (0%) | 0/35 (0%) | ||||
| FLUID OVERLOAD | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| HYPOKALAEMIA | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| HYPOGLYCAEMIA | 0/134 (0%) | 1/45 (2.2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Gout | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| ANY EVENT | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| CHONDROCALCINOSIS PYROPHOSPHATE | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| ANY EVENT | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| HEPATIC CANCER | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Gallbladder adenocarcinoma | 0/134 (0%) | 0/45 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Nervous system disorders | ||||||||
| ANY EVENT | 1/134 (0.7%) | 0/45 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| CARPAL TUNNEL SYNDROME | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| CEREBRAL MICROANGIOPATHY | 0/134 (0%) | 0/45 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| NEURALGIA | 0/134 (0%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Metabolic encephalopathy | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Psychiatric disorders | ||||||||
| ANY EVENT | 2/134 (1.5%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| CONFUSIONAL STATE | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| MENTAL STATUS CHANGES | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Renal and urinary disorders | ||||||||
| ANY EVENT | 2/134 (1.5%) | 3/45 (6.7%) | 2/36 (5.6%) | 3/35 (8.6%) | ||||
| RENAL FAILURE CHRONIC | 2/134 (1.5%) | 2/45 (4.4%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| GLOMERULONEPHRITIS CHRONIC | 0/134 (0%) | 0/45 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| DIABETIC NEPHROPATHY | 0/134 (0%) | 1/45 (2.2%) | 0/36 (0%) | 0/35 (0%) | ||||
| RENAL FAILURE | 0/134 (0%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| RENAL IMPAIRMENT | 0/134 (0%) | 0/45 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| ANY EVENT | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Asthma | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Vascular disorders | ||||||||
| ANY EVENT | 2/134 (1.5%) | 0/45 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| DIABETIC VASCULAR DISORDER | 0/134 (0%) | 0/45 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| HYPERTENSION | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| ORTHOSTATIC HYPOTENSION | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hypotension | 1/134 (0.7%) | 0/45 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| rhEPO-Naive GSK1278863 | rhEPO-Naive Control | rhEPO-User GSK1278863 | rhEPO-User Control | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 47/134 (35.1%) | 14/45 (31.1%) | 20/36 (55.6%) | 13/35 (37.1%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/134 (0%) | 1/45 (2.2%) | 3/36 (8.3%) | 0/35 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| DIARRHOEA | 10/134 (7.5%) | 0/45 (0%) | 0/36 (0%) | 6/35 (17.1%) | ||||
| NAUSEA | 8/134 (6%) | 1/45 (2.2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| CONSTIPATION | 5/134 (3.7%) | 1/45 (2.2%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| General disorders | ||||||||
| OEDEMA PERIPHERAL | 5/134 (3.7%) | 0/45 (0%) | 2/36 (5.6%) | 3/35 (8.6%) | ||||
| FATIGUE | 3/134 (2.2%) | 1/45 (2.2%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Asthenia | 1/134 (0.7%) | 3/45 (6.7%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Infections and infestations | ||||||||
| NASOPHARYNGITIS | 15/134 (11.2%) | 2/45 (4.4%) | 7/36 (19.4%) | 2/35 (5.7%) | ||||
| CONJUNCTIVITIS | 1/134 (0.7%) | 0/45 (0%) | 2/36 (5.6%) | 0/35 (0%) | ||||
| BRONCHITIS | 2/134 (1.5%) | 1/45 (2.2%) | 0/36 (0%) | 3/35 (8.6%) | ||||
| Investigations | ||||||||
| BLOOD PRESSURE INCREASED | 1/134 (0.7%) | 0/45 (0%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Metabolism and nutrition disorders | ||||||||
| HYPERKALAEMIA | 2/134 (1.5%) | 0/45 (0%) | 2/36 (5.6%) | 1/35 (2.9%) | ||||
| GOUT | 2/134 (1.5%) | 0/45 (0%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Hypoglycaemia | 1/134 (0.7%) | 0/45 (0%) | 2/36 (5.6%) | 1/35 (2.9%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| ARTHRALGIA | 2/134 (1.5%) | 2/45 (4.4%) | 1/36 (2.8%) | 3/35 (8.6%) | ||||
| BACK PAIN | 1/134 (0.7%) | 1/45 (2.2%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| EPISTAXIS | 3/134 (2.2%) | 0/45 (0%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| PRURITUS | 0/134 (0%) | 4/45 (8.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Vascular disorders | ||||||||
| HYPERTENSION | 2/134 (1.5%) | 1/45 (2.2%) | 4/36 (11.1%) | 1/35 (2.9%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01977573
Other Study ID Numbers:
- 113747
First Posted:
Nov 6, 2013
Last Update Posted:
Oct 12, 2018
Last Verified:
Sep 1, 2018