Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Exenatide Once Weekly in Japanese Patients with Type 2 Diabetes
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Exenatide Once Weekly in Japanese Patients with Type 2 Diabetes
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DOI：
10.1507/endocrj.k09e-147
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发表时间：
2009-11-01
影响因子：
2
通讯作者：
Linnebjerg, Helle
中科院分区：
文献类型：
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作者：
Iwamoto, Kazuya;Nasu, Risa;Linnebjerg, Helle
这项随机、安慰剂对照、双盲、平行研究评估了 30 名日本 2 型糖尿病 (T2D) 患者的安全性、耐受性、药代动力学和药效学，每周一次 (QW)，这些患者仅通过饮食和运动或联合双胍、磺酰脲类、噻唑烷二酮或这些药物的组合控制效果不佳（58.6% 男性；58 +/- 9 岁；体重指数26.3 +/- 2.9 kg/m(2)；血红蛋白 A(lc) [HbA(lc)] 7.4 +/- 0.8%；空腹血糖 [FPG] 156.1 +/- 29.1 mg/dL；T2D 持续时间 6 +/- 5 年；患者按 1:1:1 的比例随机接受皮下注射安慰剂 QW、艾塞那肽 QW 0.8 mg 或艾塞那肽 QW 2.0 mg，为期 10 周。除非另有说明，所有可评估的患者均进行了分析（安慰剂 QW，n=10；艾塞那肽 QW 0.8 mg，n=10；艾塞那肽 QW 2.0 mg，n=9）。在研究第 8 周观察到稳态血浆艾塞那肽浓度。对于可评估的药代动力学人群，艾塞那肽 QW 0.8 mg (n=8) 和艾塞那肽 QW 2.0 mg (n=5) 的几何平均值（90% 置信区间）稳态血浆浓度 (pg/mL) 分别为 81.2 (68.3-96.4) 和 344.5 (256.5-462.7)。安慰剂 QW、艾塞那肽 QW 0.8 mg 和艾塞那肽 QW 2.0 mg 的基线至第 10 周的血糖改善分别为： HbA1c(lc) (%)：-0.4 +/- 0.3、-1.0 +/- 0.7 和 - 1.5 +/- 0.7； FPG（毫克/分升）：-20.5 +/- 20.4、-25.2 +/- 10.9 和 -50.8 +/- 27.8；餐后 2 小时血浆葡萄糖偏移 (mg/dL)：-8.8 +/- 26.9、-50.0 +/- 41.1 和 -59.7 +/- 26.8（平均值 +/- SD）。没有报告严重不良事件 (AE)，也没有 AE 导致任何组的研究中止。观察到的最常见的 AE 是轻度至中度的注射部位硬结。没有严重低血糖的报道。艾塞那肽 QW 10 周的耐受性良好，并改善了控制不佳的日本 T2D 患者的短期血糖控制。
This randomized, placebo-controlled, double-blind, parallel study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of exenatide once weekly (QW) in 30 Japanese patients with type 2 diabetes (T2D) suboptimally controlled by diet and exercise alone or combined with biguanide, sulfonylurea, thiazolidinedione, or combinations of these agents (58.6% male; 58 +/- 9 years; body mass index 26.3 +/- 2.9 kg/m(2); hemoglobin A(lc) [HbA(lc)] 7.4 +/- 0.8%; fasting plasma glucose [FPG] 156.1 +/- 29.1 mg/dL; duration of T2D 6 +/- 5 years; means +/- SD). Patients were randomized in a 1: 1: 1 ratio to subcutaneous placebo QW, exenatide QW 0.8 mg, or exenatide QW 2.0 mg for 10 weeks. All evaluable patients were analyzed (placebo QW, n=10; exenatide QW 0.8 mg, n=10; exenatide QW 2.0 mg, n=9), unless otherwise stated. Steady-state plasma exenatide concentrations were observed by Week 8 of the study. For the evaluable pharmacokinetic population, geometric mean (90% confidence interval) steady-state plasma concentrations (pg/mL) were 81.2 (68.3-96.4) and 344.5 (256.5-462.7) with exenatide QW 0.8 mg (n=8) and exenatide QW 2.0 mg (n=5), respectively. Baseline-to-Week 10 glycemic improvements with placebo QW, exenatide QW 0.8 mg, and exenatide QW 2.0 mg, respectively, were: HbA(lc) (%): -0.4 +/- 0.3, -1.0 +/- 0.7, and - 1.5 +/- 0.7; FPG (mg/dL): -20.5 +/- 20.4, -25.2 +/- 10.9, and -50.8 +/- 27.8; and 2-hour postprandial plasma glucose excursions (mg/dL): -8.8 +/- 26.9, -50.0 +/- 41.1, and -59.7 +/- 26.8 (means +/- SD). No serious adverse events (AEs) were reported and no AEs led to study discontinuation in any group. The most frequent AE observed was mild-to-moderate injection site induration. No serious hypoglycemia was reported. Exenatide QW for 10 weeks was well tolerated and improved short-term glycemic control in Japanese patients with suboptimally controlled T2D.