Clinical Pharmacology Office, Japan Development Division, GlaxoSmithKline K.K., Tokyo, Japan.
Biomedical Data Sciences Department, Japan Development Division, GlaxoSmithKline K.K., Tokyo, Japan.
Clin Pharmacol Drug Dev. 2020 Nov;9(8):978-984. doi: 10.1002/cpdd.793. Epub 2020 Apr 6.
Daprodustat is a prolyl hydroxylase inhibitor that stimulates erythropoiesis in a manner similar to the natural response to hypoxia, whereby inhibition of hypoxia inducible factor (HIF) prolyl-4-hydroxylases by daprodustat ultimately results in increased levels of HIF-responsive genes. Daprodustat is under development as an emerging new class of agents for the treatment of anemia associated with chronic kidney disease (CKD). This was a single-center, single-dose, open-label, randomized, 2-way crossover study in healthy Japanese male participants consisting of 2 parts. The primary objective was to evaluate the bioequivalence (BE) between daprodustat tablet strengths (part 1) and to evaluate the food effect on the pharmacokinetics (PK) of daprodustat (part 2). A total of 64 healthy Japanese male participants were enrolled; 52 participants were included in part 1 and 12 in part 2. BE was demonstrated between the daprodustat 2-mg tablet and the daprodustat 4-mg tablet. A standard CKD meal did not have a large effect on the PK parameters of daprodustat after a single oral dose of daprodustat 4 mg. Administration of single oral doses of daprodustat 4 mg was generally well tolerated in the healthy Japanese participants, and no new safety signals were identified without regard to food.
达普司他是一种脯氨酰羟化酶抑制剂,它以类似于对缺氧的自然反应的方式刺激红细胞生成,通过达普司他抑制缺氧诱导因子 (HIF) 脯氨酰-4-羟化酶,最终导致 HIF 反应基因水平升高。达普司他作为一种新兴的治疗慢性肾脏病 (CKD) 相关贫血的新类别药物正在开发中。这是一项在健康日本男性参与者中进行的单中心、单剂量、开放标签、随机、2 向交叉研究,包括 2 部分。主要目的是评估达普司他片剂强度之间的生物等效性 (BE)(第 1 部分),并评估食物对达普司他药代动力学 (PK) 的影响(第 2 部分)。共招募了 64 名健康的日本男性参与者;52 名参与者纳入第 1 部分,12 名参与者纳入第 2 部分。达普司他 2 毫克片剂和达普司他 4 毫克片剂之间表现出 BE。在单次口服达普司他 4 毫克后,标准 CKD 餐对达普司他的 PK 参数没有很大影响。在健康的日本参与者中,单次口服达普司他 4 毫克通常具有良好的耐受性,并且无论是否进食,均未发现新的安全信号。