A randomized, repeat dose, open label, parallel group, multi-center study to evaluate the effect of daprodustat compared to darbepoetin alfa on forearm blood flow in participants with anemia of chronic kidney disease that are not dialysis dependent

INTERVENTION: 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: GSK1278863 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Product Name: daprodustat 2mg Pharmaceutical Form: Tablet INN or Proposed INN: daprodustat CAS Number: 960539‐70‐2 Current Sponsor code: GSK1278863A (A denotes the free Other descriptive name: GSK1278863 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2‐ Product Name: daprodustat 4mg Pharmaceutical Form: Tablet INN or Proposed INN: daprodustat CAS Number: 960539‐70‐2 Current Sponsor code: GSK1278863A (A denotes the free Other descriptive name: GSK1278863 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 4‐ Trade Name: Aranesp Product Name: Darbepoetin alfa Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: DARBEPOETIN ALFA CAS Number: 209810‐58‐2 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: range Concentration number: 25‐500 CONDITION: 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 Therapeutic area: Body processes [G] ‐ Physiological processes [G07] PRIMARY OUTCOME: ; 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; Main Objective: To compare the effect of daprodustat to darbepoetin alfa on endothelial function 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 OUTCOME: ; 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 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(<50% change in overall dose and compliance of 80% of prescribed doses in the 4 weeks prior to and including the screening period). If participants have been on intravenous (IV) iron, then participants will not have received IV iron for 4 weeks prior to the Day 1 visit. Sex

Epistemonikos ID: f50031d1be34786e2d455cc8c31cf7656f1098b1
First added on: Aug 24, 2024