Anemia associated with chronic kidney disease MedDRA version: 14.1 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 100000004857
Conditions
Interventions
Product Name: GSK1278863
Product Code: GSK1278863 0.1mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: GSK1278863
CAS Number: None
Current Sponsor code: GSK1278863
Other descriptive name
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrollment in the study must meet all of the following criteria as verified at Screening (Week -1): 1. Age and weight: >/= 18 years of age and >/= 45 kg. 2. Dialysis, rhEPO use and CKD: a. Not routinely undergoing dialysis, regardless of the modality (either hemodialysis or peritoneal dialysis) or dialysis planned during the time the subject would be enrolled in the study. b. No current or prior rhEPO use within the past 7 weeks; e.g., epoetins (or their biosimilars), darbepoetin, Mircera (methoxy polyethylene glycol epoetin beta), peginesatide or their biosimilars. c. KDOQI CKD stages 3/4/5 defined by eGFR using the Modification of Diet for Renal Disease (MDRD). 3. Lab inclusions a. Hgb: Hgb concentrations 8.5-11.0 g/dL (inclusive) as outlined in Section 4.2. b. Vitamin B12: Above the lower limit of the reference range (may rescreen in 2 months). c. Folate: =2.0 ng/mL at Screening (may rescreen in a month). d. Ferritin: =40 ng/mL with the absence of microcytic or hypochromic RBCs. e. TSAT within the reference range. 4. Iron replacement therapy: Stable maintenance dose of oral iron replacement therapy, if required, that will be maintained throughout the study. NOTE: IV iron replacement therapy is not allowed the two weeks prior to Screening through the end of the study (Week 6). 5. QTc: QTcB 40 MIU/ml and estradiol =65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: CKD-related criteria 1.Dialysis: Planning to initiate dialysis during the study or who have a high potential for initiating dialysis during study participation. 1.Renal transplant: Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant. 2.Laboratory exclusions a.Total CPK: >5x the upper limit of the reference range. b.HIV: Positive HIV antibody. Cardiovascular disease-related criteria 3.Prior CV events a.History of myocardial infarction or acute coronary syndrome within the prior 6 months. b.History of stroke or transient ischemic attacks (TIAs) within the prior 6 months. 4.Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system. 5.Hypertension: Poorly controlled hypertension, whether due to inadequate treatment, or lack of treatment, defined as DBP >100 mmHg or SBP>160 mmHg. 6.Thrombotic disease: History of thrombotic disease (e.g., venous thrombosis such as deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset or worsening limb ischemia requiring intervention), or other thrombosis related condition, within the prior 6 months. 7.Pulmonary hypertension: Known pulmonary hypertension and those at higher risk (than normally associated with CKD) for pre-existing elevation in pulmonary pressure (e.g., significant heart failure or lung disease requiring supplemental oxygen, or those with connective tissue diseases). Other disease-related criteria 8.Inflammatory disease: Chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease). 9.Hematological disease: Any hematological disease including those affecting platelets, the coagulation disorders (e.g., Protein C or S deficiency) or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia) or any other cause of anemia other than renal disease. 10.Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones) or evidence at Screening of abnormal liver function tests [alkaline phosphatase, ALT or AST > 2.0 x upper limit of normal (ULN) or total bilirubin > 1.5 x ULN]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study. NOTE: Those Hepatitis C positive are eligible provided these laboratory exclusions are not met. 11.Major surgery: Within the prior 12 weeks or planned during the study. 12.Transfusion: Blood transfusion within the prior 12 weeks or an anticipated need for blood transfusion during the study. 13.Ulcer and Active GI Bleeding: Evidence of active peptic, duodenal, or esophageal ulcer disease or active GI bleeding within the prior 12 weeks. 14.Acute infection: Clinical evidence of acute infection or history of infection requiring intravenous (IV) antibiotic therapy the eight weeks prior to Screening through Day 1 (randomization). NOTE: IV antibiotics as prophylaxis are allowed. 15.Malignancy: History of malignancy within 5 years of Screening or are receiving treatment for cancer or those with a strong family history of cancer (e.g., familial cancer disorders), with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated. 16.Hyperparathyroid
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Estimate the relationship between dose of GSK1278863 and Hgb response for correcting anemia in non-dialysis subjects with CKD who are not taking rhEPO.;Secondary Objective: Secondary Objectives • Characterize the effect of GSK1278863 on additional measures of Hgb response. • Characterize the effect of GSK1278863 on erythropoietin (EPO), measures of iron metabolism and utilization (hepcidin, ferritin, transferrin, transferrin saturation, total iron, Total Iron Binding Capacity (TIBC)), a measure of inflammation (high sensitivity C-Reactive Protein; hsCRP), and vascular endothelial growth factor (VEGF). • Characterize the steady-state pharmacokinetics (PK) of GSK1278863 and relevant metabolites and evaluate the exposure-response relationship between GSK1278863 and pharmacodynamic (PD) endpoints. • Assess the safety and tolerability of GSK1278863 following once-daily (QD) administration for 4 weeks. ;Primary end point(s): Modelled Hgb change from baseline over 4 weeks of treatment.;Timepoint(s) of evaluation of this end point: 4 weeks after starting treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Maximum Hgb changes over 4 weeks. • Number and percentage of subjects who achieve an Hgb response (defined as achieving an increase of at least 0.5 g/dL, 1.0 g/dL, 1.5 g/dL and 2.0g/dL in Hgb during the trial). • Number of subjects who have reached Hgb stopping criteria. • Evaluation of change in markers of iron metabolism and utilization (hepcidin, ferritin, transferrin, transferrin saturation, total iron, TIBC) and a measure of inflammation (hsCRP). • Evaluation of change in EPO, hematocrit, RBC, reticulocytes, VEGF plasma concentrations. • Population pharmacokinetic parameters of GSK1278863 and relevant metabolites. • Discontinuation for safety related reasons, e.g. pre-specified stopping criteria or AE. • Incidence and severity of AEs and SAEs. • Absolute values and changes from baseline over time in laboratory parameters, ECGs and vital signs. ;Timepoint(s) of evaluation of this end point: After 4 weeks of treatment as well as the timecourse (Week 1, 2 and 3). | — |
Countries
Canada, Germany, United States
Contacts
Public ContactClincial Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed