Kansai Electric Power Hospital, Osaka, Japan.
Curr Med Res Opin. 2009 Dec;25(12):3049-57. doi: 10.1185/03007990903372999.
To investigate safety, pharmacokinetics and pharmacodynamics of albiglutide in Japanese subjects with type 2 diabetes mellitus.
This randomized, single-blind, placebo-controlled study examined four doses/dose schedules of subcutaneously (sc) administered albiglutide: 15 mg weekly, 30 mg weekly, 50 mg biweekly, and 100 mg monthly (cohorts A-D, respectively) in 40 subjects (mean age 54.5 years, mean range of glycosylated hemoglobin [HbA(1c)] 7.1-8.3%), over a 4-week treatment period.
Safety parameters, including adverse events, clinical laboratory tests, vital signs, and 12-lead electrocardiogram; plasma concentrations of albiglutide; and pharmacodynamic parameters, including change from baseline and weighted mean AUC(0-4) in plasma glucose, glucagon, insulin, and C-peptide levels.
NCT00530309.
At day 29, mean changes from baseline (vs. placebo) in fasting plasma glucose (FPG) were: cohort A, -1.92 mmol/L; B, -1.98 mmol/L; C, -1.74 mmol/L; D, -0.73 mmol/L; changes in weighted mean glucose AUC(0-4) were: cohort A, -2.86 mmol/L; B, -3.58 mmol/L; C, -2.51 mmol/L; D, -1.44 mmol/L (for FPG and AUC(0-4), all p < or = 0.002 except 100 mg sc monthly, p = NS); changes from baseline HbA(1c) were: cohort A, -0.58%; B, -0.57%; C, -0.63%; and D, -0.51% (all p < 0.03). Albiglutide sc had a median half-life of 5.3 days, plasma apparent systemic clearance of 68.7 mL/h, and apparent volume of distribution of 12.6 L. Incidence of adverse events was low and comparable to sc placebo in all albiglutide treatment arms except 100 mg sc monthly, where gastrointestinal (GI) adverse events were most common. Limitations of this study include the small sample size, short treatment duration, and enrollment of predominantly male subjects.
Weekly and biweekly albiglutide improved glycemic control and were well-tolerated in Japanese subjects with type 2 diabetes mellitus.
研究 albiglutide 在日本 2 型糖尿病患者中的安全性、药代动力学和药效学。
这是一项随机、单盲、安慰剂对照的研究，共纳入 40 例受试者（平均年龄 54.5 岁，平均糖化血红蛋白 [HbA1c] 范围 7.1-8.3%），分别接受皮下注射（sc） albiglutide 四种剂量/给药方案：15 mg 每周、30 mg 每周、50 mg 每两周和 100 mg 每月（分别为队列 A、B、C 和 D），治疗期为 4 周。
安全性参数，包括不良事件、临床实验室检查、生命体征和 12 导联心电图；albiglutide 的血浆浓度；以及血糖、胰高血糖素、胰岛素和 C 肽水平的基线变化和加权平均 AUC（0-4）等药效学参数。
NCT00530309。
在第 29 天，与安慰剂相比，空腹血糖（FPG）的平均变化（vs. 安慰剂）为：队列 A，-1.92 mmol/L；B，-1.98 mmol/L；C，-1.74 mmol/L；D，-0.73 mmol/L；加权平均血糖 AUC（0-4）的变化为：队列 A，-2.86 mmol/L；B，-3.58 mmol/L；C，-2.51 mmol/L；D，-1.44 mmol/L（除 sc 每月 100mg 外，所有均 p < or = 0.002，p = NS）；HbA1c 的基线变化为：队列 A，-0.58%；B，-0.57%；C，-0.63%；D，-0.51%（均 p < 0.03）。Albiglutide sc 的中位半衰期为 5.3 天，血浆表观系统清除率为 68.7 mL/h，表观分布容积为 12.6 L。除 sc 每月 100mg 外，所有 albiglutide 治疗组的不良事件发生率均较低，且与 sc 安慰剂相当，sc 每月 100mg 组最常见的不良事件为胃肠道（GI）不良事件。本研究的局限性包括样本量小、治疗时间短以及主要纳入男性受试者。
每周和每两周一次的 albiglutide 可改善日本 2 型糖尿病患者的血糖控制，且耐受性良好。
