Anemia associated with chronic kidney disease. MedDRA version: 16.0 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 100000004857
Conditions
Sponsors
GlaxoSmithKline, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age: >or=18 years of age. 2. Gender: Female and male subjects - Females: If of childbearing potential, must agree to use one of the approved contraception methods as outlined in Section 11.6 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 [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0-116.3 IU/L and estradiol =65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: Subjects are not eligible if they meet any of the following criteria. CKD-related criteria 1. Dialysis: On dialysis or planning to initiate dialysis during the study 2. Renal transplant: Pre-emptive or scheduled renal transplant 3. High rhEPO dose: An epoetin dose of >or=360 IU/kg/week IV or darbepoetin dose of >or=1.8 ?g/kg/week IV within the prior 8 weeks through Day 1 4. Mircera: Use of Mircera (methoxy polyethylene glycol epoetin beta) within the prior 8 weeks through Day 1 5. 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 Laboratory test-based criteria (Week -4 verification only) 6. Vitamin B12: Below the lower limit of the reference range 7. Folate: 100 mmHg or SBP>170 mmHg at Week -4 and reconfirmed at Day 1 14. Thrombotic Disease: History of thrombotic disease, except vascular access thrombosis within the 8 weeks prior to Week -4 Screening through Day 1 Other disease-related criteria 15. Ophthalmology disease: Meeting any ophthalmologic-related exclusion criteria determined at the Screening ophthalmology exam 16. Inflammatory disease: Active chronic inflammatory disease that could impact erythropoiesis diagnosed prior to Week -4 Screening through Day 1 17. Hematological disease: Any hematological disease including those affecting platelets, white or red blood cells, coagulation disorders, or any other cause of anemia other than renal disease diagnosed prior to Week -4 Screening through Day 1 18. Liver disease: Current liver disease, known hepatic or biliary abnormalities 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. 19. Major surgery: Major surgery within the prior 8 weeks, during the Week -4 Screening phase or planned during the study 20. Transfusion: Blood transfusion within the prior 8 weeks, during the Week -4 Screening phase or an anticipated need for blood transfusion during the study 21. 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 22. Acute infection: Clinical evidence of acute infection or history of infection requiring intravenous (IV) antibiotic therapy within the 8 weeks prior to Week -4 Screening through Day 1 23. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Characterize the ability of GSK1278863 to achieve mean Hgb response within the target range (9.0 to 10.5 g/dL)hemoglobin change from baseline at week 24.;Secondary Objective: -Characterize the ability of GSK1278863 to achieve Hgb within the target range at week 12 and 24 (% in range). -Characterize the effect of GSK1278863 on measures of iron metabolism and utilization, on indices of hematopoiesis, EPO, and on Vascular Endothelial Growth Factor (VEGF). -Characterize the steady-state population PK of GSK1278863 and metabolites -Evaluate the GSK1278863 dose adjustment scheme.;Primary end point(s): Hemoglobin change from baseline at Week 24.;Timepoint(s) of evaluation of this end point: week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in hepcidin, ferritin, transferrin, transferrin saturation, total iron, total iron binding capacity (TIBC), reticulocyte Hgb (CHr), %hypochromic red blood cells (RBCs) at Week 24. - Change from baseline in hematocrit, RBC, reticulocyte number at Week 24. - Maximum observed change from baseline in EPO. - Maximum observed change from baseline in VEGF. - Population plasma PK parameters of GSK1278863 and metabolites. - Number, frequency and timing of dose adjustments. - Total cumulative and final dose. - Number of Hgb excursions, Hgb cycles and dose cycles. - Number (%) of subjects with at least one Hgb excursion. - Number (%) of subjects with at least one Hgb cycle. - Number (%) of subjects with at least one dose cycle. - Time that dose is held because Hgb exceeded upper limits. - Number (%) of subjects receiving additional therapies of blood transfusions, IV iron or rhEPO.;Timepoint(s) of evaluation of this end point: Week 24 | — |
Countries
Australia, Canada, Czech Republic, Denmark, Hungary, Japan, Korea, Republic of, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed