anemia associated with chronic kidney disease MedDRA version: 21.1 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: daprodustat 1mg
Pharmaceutical Form: Tablet
INN or Proposed INN: daprodustat
CAS Number: 960539-70-2
Current Sponsor code: GSK1278863A (A denotes the free
Other descriptive name: GSK1278
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 1. Participant must be at least 18 years of age inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. Participants who are Stage 3, 4 or 5 CKD defined by eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula (Levey, 2009). 3. Hgb as measured by HemoCue at screening visit and Day 1 is = 11.0 g/dL (= 110 g/L). 4. Palpable brachial artery as assessed at screening. 5. Participants,if necessary, may be on stable maintenance oral iron supplementation supplementation(=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Medical Conditions 1. On dialysis or clinical evidence of impending need to initiate dialysis within 12 weeks of Day 1. 2. Planned kidney transplant within 12 weeks of Day 1. 3. Presence of an arteriovenous (AV) fistula. Prior/Concomitant Therapy 4. rhEPO use within the 12 weeks prior to the screening visit and through Day 1. 5. History of severe allergic or anaphylactic reactions or hypersensitivity to the study treatment or challenge agents, or excipients in the study treatments or challenge agents (see daprodustat IB for list of excipients, and the Study Reference Manual (SRM) for product sheets for darbepoetin alfa and the challenge agents). 6. Planned use of any prescription or non-prescription drugs or dietary supplements that are prohibited from screening until all assessments on Day 42 have been successfully completed (see Section 7.7.2 of the study protocol). Prior/Concurrent Clinical Study Experience 7. The participant has participated in a clinical trial and has received an experimental investigational product within the prior 30 days or within 5 half lives of the investigational product (whichever is longer) prior to screening and through Day 1. Diagnostic assessments 8. At or below the lower limit of the reference range at screening for Vitamin B12 (may rescreen in a minimum of 8 weeks). 9. Ferritin = 50 ng/mL (= 50 µg/L) at screening. 10. Transferrin saturation (TSAT) = 15% (0.15) at screening. 11. Folate 170 mmHg or diastolic blood pressure > 100 mmHg at screening visit or current uncontrolled hypertension as determined by the investigator. 18. QT interval corrected for heart rate using Bazett’s formula (QTcB): QTcB >500 msec, or QTcB >530 msec in participants with bundle branch block. There is no QTc exclusion for participants with a predominantly ventricular paced rhythm. 19. Active chronic inflammatory disease that could impact erythropoiesis. A partial list can be found in the Study Reference Manual (SRM). 20. History of bone marrow aplasia or pure red cell aplasia. 21. Conditions, other than anemia of CKD, which can affect erythropoiesis. A partial list can be found in the SRM. 22. Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding from = 8 weeks prior to screening and through Day 1. 23. Liver disease (any of the following): -Alanine transaminase (ALT) > 2x upper limit of normal (ULN; screening only) -Bilirubin > 1.5x ULN (screening only) NOTE: Isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35% -Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 24. Major surgery within the 12 weeks prior to screening and through Day 1, or planned during the study. 25. Anticipated or planned vascular access surge
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effect of daprodustat to darbepoetin alfa on endothelial function;Secondary Objective: -To further compare the effect of daprodustat to darbepoetin alfa on endothelial function -To compare the effect of daprodustat to darbepoetin alfa on endothelium-independent vasodilation -To compare the effect of daprodustat to darbepoetin alfa on basal endothelial NO synthesis -To compare the effect of daprodustat on the FBF response to acetylcholine, sodium nitroprusside and L-NMMA between Day 42 and Day 1 -To compare the effect of darbepoetin alfa on the FBF response to acetylcholine, sodium nitroprusside and L-NMMA between Day 42 and Day 1 -To compare the effect of daprodustat to darbepoetin alfa on vascular compliance -Assess safety and tolerability;Primary end point(s): Change in FBF ratio from Day 1 to Day 42 in response to acetylcholine;Timepoint(s) of evaluation of this end point: Day 1 and Day 42 of treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Change in the absolute FBF from Day 1 to Day 42 in response to acetylcholine -Change in FBF ratio from Day 1 to 42 in response to sodium nitroprusside -Change in the absolute FBF from Day 1 to Day 42 in response to sodium nitroprusside -Change in FBF ratio from Day 1 to Day 42 in response to L-NMMA -Change in the absolute FBF from Day 1 to Day 42 in response to LNMMA -Change in FBF ratio in response to each individual challenge agent at Day 42 vs Day 1 in participants treated with daprodustat -Change in the absolute FBF in response to each individual challenge agent at Day 42 vs Day 1 in participants treated with daprodustat -Change in FBF ratio in response to each individual challenge agent at Day 42 vs Day 1 in participants treated with darbepoetin alfa -Change in the absolute FBF in response to each individual challenge agent at Day 42 vs Day 1 in participants treated with darbepoetin alfa -Change in Augmentation Index (an indicator of arterial stiffness) as estimated by radial arterial pulse contours from Day 1 to 42 -Change in pulse wave velocity (PWV) from Day 1 to Day 42 (AEs) and serious adverse events (SAEs) including AEs of special interest -Reasons for discontinuation of randomized study treatment -Absolute values and changes from baseline in clinical laboratory parameters, ECG parameters, blood pressure (BP) and heart rate (HR);Timepoint(s) of evaluation of this end point: Day 1 and Day 42 of treatment period | — |
Countries
United Kingdom
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed