Anemia associated with chronic kidney disease MedDRA version: 18.1 Level: LLT Classification code 10002272 Term: Anemia System Organ Class: 100000004851
Conditions
Interventions
Product Name: GSK1278863
Product Code: GSK1278863
Pharmaceutical Form: Tablet
INN or Proposed INN: GSK1278863
Current Sponsor code: GSK1278863
Other descriptive name: GSK1278863
Concentration unit: mg
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: AGE 1. >=18 years of age, at the time of signing the informed consent. TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY 2. Hemoglobin: Stable Hgb 9.0 - 11.5 g/dL (see Section 5.1 of study protocol). 3. Dialysis frequency: On hemodialysis (HD, hemofiltration or hemodiafiltration) three to five times weekly for at least 4 weeks prior to Day -28 Screening through Day 29. 4. Dialysis adequacy: A single pool Kt/Vurea of ? 1.2 based on a historical value obtained within the prior three months 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%. NOTE: Only needs confirming at Day -28. 5. ESA dose: Treated with the same ESA (epoetins or their biosimilars, or darbepoetin or methoxy PEG-epoetin beta) with total weekly dose varying by no more than 50% during the 4 weeks prior to Day -28. 6. Iron replacement therapy: Subjects may be on stable maintenance oral or IV (?100mg/week) iron supplementation. If subjects are on oral or IV iron, then doses must be stable for the 4 weeks prior to Day -28, during the screening phase, and through the 29 days of treatment. INFORMED CONSENT 7. Capable of giving signed informed consent as described in Section 10.2 of study ptotocol which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: CKD-RELATED CRITERIA 1. Dialysis modality: Planned change from HD to peritoneal dialysis within the study time period. 2. Renal transplant: Planned for living-related kidney transplant. 3. High ESA dose: An epoetin dose of >=360 IU/kg/week IV or >=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 µg /kg/week IV or SC or methoxy PEG-epoetin beta dose of 2.2 µg /kg/week within the prior 8 weeks through Day 1 (randomization). 4. Mircera: Administration of Mircera (methoxy PEG-epoetin beta) within the prior 4 weeks through Day 1 (randomization). CARDIOVASCULAR DISEASE-RELATED CRITERIA 5. Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to Screening through Day 1 (randomization). 6. Stroke or transient ischemic attack: Within 8 weeks prior to Screening though Day 1 (randomization). 7. Heart failure: Class IV heart failure, as defined by the New York Heart Association functional classification system diagnosed prior to Screening through Day 1 (randomization). 8. QTcB: QTcB >500 msec or QTcB >530 msec in subjects with Bundle Branch Block. There is no QTc exclusion for subjects with a predominantly paced rhythm. OTHER DISEASE-RELATED CRITERIA 9. Inflammatory disease: Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) diagnosed prior to Screening through Day 1 (randomization). 10. 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 of chronic disease other than renal disease diagnosed prior to Screening though Day 1 (randomization). 11. 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) >2x upper limit of normal (ULN) or total bilirubin >1.5xULN]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participating in the study. NOTE: Those with Hepatitis B or Hepatitis C are eligible provided these exclusions are not met. 12. Major surgery: Major surgery (excluding vascular access surgery) within the 8 weeks prior to Screening, during the Screening phase, or planned during the study. 13. Transfusion: Blood transfusion within the 8 weeks prior to Screening, during the Screening phase or an anticipated need for blood transfusion during the study. 14. GI Bleeding: Evidence of actively bleeding peptic, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within the 8 weeks prior to Screening through Day 1 (randomization). 15. Acute Infection: Clinical evidence of acute infection or history of infection requiring intravenous (IV) antibiotic therapy within the 4 weeks prior to Screening through Day 1 (randomization). 16. Malignancy: History of malignancy within the two years prior to randomization or currently receiving treatment for cancer, or has a known > 4 cm complex kidney cyst (i.e. Bosniak Category II F, III of IV). CONCOMITANT MEDICATIONS 17. Severe allergic reactions: History of severe allergic or anaphylactic reactions or hyper
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -Characterize the dose-response relationship between GSK1278863 administered threetimes weekly and Hgb at Day 29.;Secondary Objective: -Characterize the pharmacodynamic (PD) effect of GSK1278863 dose regimens on EPO, vascular endothelial growth factor (VEGF), hepcidin and red blood cells. -Characterize the steady-state PK of GSK1278863 and major metabolites. - Assess the safety and tolerability of GSK1278863 with three-times weekly administration for 29 days.;Primary end point(s): Hgb change from baseline;Timepoint(s) of evaluation of this end point: Day 29 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Maximum observed change from baseline in EPO -Maximum observed % change from baseline in VEGF - Change from baseline in hepcidin at Day 29 - Change from baseline in hematocrit, red blood cell (RBC) count, reticulocyte count and reticulocyte Hgb (CHr) at Day 29 -Descriptive PK summaries of GSK1278863 and major metabolites - Incidence and severity of AEs and SAEs - Reasons for discontinuation of investigational product -Discontinuation for safety-related reasons, e.g., pre-specified stopping criteria or AE -Absolute values and changes from baseline over time in laboratory parameters, ECGs and vital signs;Timepoint(s) of evaluation of this end point: 29 Days | — |
Countries
Canada, Russian Federation, Spain, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed