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Abstract：
Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates genes related to iron metabolism. The efficacy (noninferiority) and safety of daprodustat compared with standard therapy (darbepoetin alfa) was evaluated.
This was a randomized, phase 3, double-blind, active-control study in Japanese patients receiving hemodialysis with anemia of CKD. Participants\' treatment was switched from current erythropoiesis-stimulating agents (ESAs) to daprodustat 4 mg once daily or darbepoetin alfa 10-60 μg once weekly (on the basis of the prestudy ESA dose). Dose was adjusted every 4 weeks for daprodustat or every 2 weeks for darbepoetin alfa, according to a protocol-specified algorithm. The primary end point was mean hemoglobin during weeks 40-52 in the intent-to-treat population.
Of 332 participants screened, 271 participants were randomized (safety evaluation: 271 participants; efficacy evaluation: 267 intent-to-treat population). The mean hemoglobin during weeks 40-52 were maintained within the target range in both groups (10.9 g/dl [95% confidence interval (95% CI), 10.8 to 11.0] for daprodustat, and 10.8 g/dl [95% CI, 10.7 to 11.0] for darbepoetin alfa). Daprodustat was noninferior to darbepoetin alfa, as the lower bound of the confidence interval for the treatment difference (0.1 g/dl; 95% CI, -0.1 to 0.2 g/dl) was greater than the noninferiority criterion of -1.0 g/dl. For most participants, hemoglobin was maintained within the target range (10.0-12.0 g/dl) during weeks 40-52 (88% daprodustat; 90% darbepoetin alfa). Geometric mean hepcidin levels decreased more at week 52 with daprodustat (-37%; 95% CI, -49 to -23) than with darbepoetin alfa (-20%; 95% CI, -36 to -1), and an increase in total iron-binding capacity was observed in the daprodustat group. Frequency of adverse events were generally similar between daprodustat and darbepoetin alfa.
Oral daprodustat was noninferior to darbepoetin alfa as measured by mean hemoglobin over weeks 40-52 in Japanese patients receiving hemodialysis switched from ESAs.
201754, Clinicaltrials.gov, NCT02969655.
This was a randomized, phase 3, double-blind, active-control study in Japanese patients receiving hemodialysis with anemia of CKD. Participants\' treatment was switched from current erythropoiesis-stimulating agents (ESAs) to daprodustat 4 mg once daily or darbepoetin alfa 10-60 μg once weekly (on the basis of the prestudy ESA dose). Dose was adjusted every 4 weeks for daprodustat or every 2 weeks for darbepoetin alfa, according to a protocol-specified algorithm. The primary end point was mean hemoglobin during weeks 40-52 in the intent-to-treat population.
Of 332 participants screened, 271 participants were randomized (safety evaluation: 271 participants; efficacy evaluation: 267 intent-to-treat population). The mean hemoglobin during weeks 40-52 were maintained within the target range in both groups (10.9 g/dl [95% confidence interval (95% CI), 10.8 to 11.0] for daprodustat, and 10.8 g/dl [95% CI, 10.7 to 11.0] for darbepoetin alfa). Daprodustat was noninferior to darbepoetin alfa, as the lower bound of the confidence interval for the treatment difference (0.1 g/dl; 95% CI, -0.1 to 0.2 g/dl) was greater than the noninferiority criterion of -1.0 g/dl. For most participants, hemoglobin was maintained within the target range (10.0-12.0 g/dl) during weeks 40-52 (88% daprodustat; 90% darbepoetin alfa). Geometric mean hepcidin levels decreased more at week 52 with daprodustat (-37%; 95% CI, -49 to -23) than with darbepoetin alfa (-20%; 95% CI, -36 to -1), and an increase in total iron-binding capacity was observed in the daprodustat group. Frequency of adverse events were generally similar between daprodustat and darbepoetin alfa.
Oral daprodustat was noninferior to darbepoetin alfa as measured by mean hemoglobin over weeks 40-52 in Japanese patients receiving hemodialysis switched from ESAs.
201754, Clinicaltrials.gov, NCT02969655.
摘要：
Daprodustat是一种口服缺氧诱导因子脯氨酸酰羟化酶抑制剂，可刺激红细胞生成并调节与铁代谢相关的基因。与标准疗法（darbepoetinalfa）相比，评估了daprodustat的疗效（非劣效性）和安全性。
这是一个随机的，第三阶段，双盲，日本血液透析合并CKD贫血患者的主动对照研究。参与者的治疗从目前的红细胞生成刺激剂（ESA）改为每天一次4mgdaprodustat或每周一次10-60μgdarbepoetinalfa（根据研究前的ESA剂量）。daprodustat每4周调整剂量，darbepoetinalfa每2周调整剂量，根据协议指定的算法。主要终点是意向治疗人群40-52周期间的平均血红蛋白。
在筛查的332名参与者中，271名参与者被随机分配（安全性评估：271名参与者；疗效评估：267名意向治疗人群）。两组40-52周的平均血红蛋白均维持在目标范围内（10.9g/dl[95％置信区间（95％CI），10.8to11.0]fordaprodustat,darbepoetinalfa为10.8g/dl[95%CI，10.7至11.0])。达普罗杜坦不劣于达贝波汀阿尔法，因为治疗差异的置信区间下限（0.1g/dl;95％CI，-0.1至0.2g/dl）大于-1.0g/dl的非劣效性标准。对于大多数参与者来说,在40-52周期间,血红蛋白维持在目标范围(10.0-12.0g/dl)内(88%daprodustat;90%darbepoetinalfa).在第52周，daprodustat的几何平均hepcidin水平下降更多（-37％；95％CI，-49至-23），而darbepoetinalfa（-20％；95％CI，-36至-1），在daprodustat组中观察到总铁结合能力增加。daprodustat和darbepoetinalfa之间的不良事件频率通常相似。
在接受从ESA转换的血液透析的日本患者中，口服daprodustat在40-52周的平均血红蛋白测量结果不劣于darbepoetinalfa。
201754,Clinicaltrials.gov,NCT02969655。
这是一个随机的，第三阶段，双盲，日本血液透析合并CKD贫血患者的主动对照研究。参与者的治疗从目前的红细胞生成刺激剂（ESA）改为每天一次4mgdaprodustat或每周一次10-60μgdarbepoetinalfa（根据研究前的ESA剂量）。daprodustat每4周调整剂量，darbepoetinalfa每2周调整剂量，根据协议指定的算法。主要终点是意向治疗人群40-52周期间的平均血红蛋白。
在筛查的332名参与者中，271名参与者被随机分配（安全性评估：271名参与者；疗效评估：267名意向治疗人群）。两组40-52周的平均血红蛋白均维持在目标范围内（10.9g/dl[95％置信区间（95％CI），10.8to11.0]fordaprodustat,darbepoetinalfa为10.8g/dl[95%CI，10.7至11.0])。达普罗杜坦不劣于达贝波汀阿尔法，因为治疗差异的置信区间下限（0.1g/dl;95％CI，-0.1至0.2g/dl）大于-1.0g/dl的非劣效性标准。对于大多数参与者来说,在40-52周期间,血红蛋白维持在目标范围(10.0-12.0g/dl)内(88%daprodustat;90%darbepoetinalfa).在第52周，daprodustat的几何平均hepcidin水平下降更多（-37％；95％CI，-49至-23），而darbepoetinalfa（-20％；95％CI，-36至-1），在daprodustat组中观察到总铁结合能力增加。daprodustat和darbepoetinalfa之间的不良事件频率通常相似。
在接受从ESA转换的血液透析的日本患者中，口服daprodustat在40-52周的平均血红蛋白测量结果不劣于darbepoetinalfa。
201754,Clinicaltrials.gov,NCT02969655。
