Anaemia associated with chronic kidney disease MedDRA version: 15.1 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 100000004857
Conditions
Interventions
Product Name: GSK1278863
Product Code: GSK1278863
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: GSK1278863
CAS Number: None
Current Sponsor code: GSK1278863
Other descriptive name: GSK1
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 (weight post-dialysis). 2. Hemodialysis: a. On three times weekly hemodialysis for at least 8 weeks, irrespective of eGFR values and stage of CKD. b. A single-pool Kt/Vurea of >/=1.2 based on a historical value obtained within the prior month in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio (URR) of at least 65%. 3. rhEPO use: Using the same rhEPO (epoetins or their biosimilars, or darbepoetin) with total weekly doses that varied by no more than 50% during the prior 4 weeks (i.e., maximum vs. minimum total weekly doses /= 2.0 ng/mL (may rescreen in one month). d. Ferritin: >/=40 ng/mL with the absence of microcytic or hypochromic RBCs. e.Transferrin saturation (TSAT): Within the reference range. 5.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). 6.QTc: QTcB 40MIU/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 modality: On peritoneal dialysis OR planned change in dialysis modality within the study time period. 2.rhEPO Hyporesponders: As defined by an epoetin dose of >/=360 IU/kg/week IV or darbepoetin dose of >/=1.8 µg/kg/week IV within the prior 8 weeks. 3.Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant. 4. Mircera or Peginesatide: Current or prior use (within the prior 8 weeks) of Mircera (methoxy polyethylene glycol epoetin beta) OR peginesatide. 5.Lab Exclusions: a.Total CPK: >5x the upper limit of the reference range. b.HIV: Positive HIV antibody. 6.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. 7.Heart failure: Class III/IV heart failure, (NYHA) functional classification system. 8.Hypertension: Poorly controlled hypertension, whether due to inadequate treatment, or lack of treatment 9.Thrombotic Disease: History of thrombotic disease, or other thrombosis related condition except shunt thrombosis within the prior 6 months. 10.Pulmonary hypertension: Known pulmonary hypertension and those at higher risk (than normally associated with CKD) for pre-existing elevation in pulmonary pressure. 11.Inflammatory disease: Chronic inflammatory disease that could impact erythropoiesis. 12.Haematological disease: Any haematological disease including those affecting platelets, the coagulation disorders or red blood cells or any other cause of anemia other than renal disease. 13.Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones) or evidence at Screening of abnormal liver function tests [alkaline phosphatase, 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. NOTE: Those Hepatitis C positive are eligible provided these laboratory exclusions are not met. 14.Major surgery: Within the prior 12 weeks or planned during the study. 15.Transfusion: Blood transfusion within the prior 12 weeks or an anticipated need for blood transfusion during the study. 16.Ulcer and Active GI Bleeding: Evidence of active peptic, duodenal, or esophageal ulcer disease OR GI bleeding within the prior 12 weeks. 17.Acute infection: Clinical evidence of acute infection or history of infection requiring intravenous (IV) antibiotic therapy the eight weeks prior to Screening through Day 1 (randomization). NOTE: IV antibiotics as prophylaxis are allowed. 18.Malignancy: History of malignancy within the prior 5 years or are receiving treatment for cancer or those with a strong family history of cancer, with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated. 19.Eyes: History of proliferative retinopathy requiring treatment within the prior 12 months or macular edema requiring treatment. 20.Severe reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product (refer to GSK1278863 IB). 21.Drugs and supplements: Use of any prescription or non-prescription drugs or dietary supplements that are prohibited
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Estimate the relationship between dose of GSK1278863 and hemoglobin (Hgb) response following switching from a stable dose of rhEPO in subjects undergoing HDD.;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 Objective: Secondary Objectives • Characterize the effect of GSK1278863 on additional measures of Hgb response. • Characterize the effect of GSK1278863 on 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 population PK of GSK1278863 and relevant metabolites. •Assess the safety and tolerability of GSK1278863 following QD administration for 4 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Endpoints to describe Hgb variability over the 4 weeks include: -Within subject standard deviation (SD). -Residual SD - derived from a regression model. -Time spent with Hgb within range (where range will be defined as ±0.5 g/dL and ±1 g/dL from baseline Hgb). -Area Under the Hgb Change versus time Curve (AUC) – using change from baseline. -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 PK 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, Denmark, Germany, Norway, Sweden, United States
Contacts
Public ContactClincial Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed