AIMS To report phase 1 bioequivalence results comparing MYL-1501D, US reference insulin glargine (US IG), and European reference insulin glargine (EU IG). MATERIALS AND METHODS The double-blind, randomized, three-way crossover study compared the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of MYL-1501D, US IG and EU IG. In total, 114 patients with type 1 diabetes (T1DM) received 0.4 U/kg of each study treatment under automated euglycaemic clamp conditions. Insulin metabolite M1 concentrations, insulin glargine (IG) and glucose infusion rates (GIRs) were assessed over 30 hours. Primary PK endpoints were area under the serum IG concentration-time curve from 0 to 30 hours (AUCins.0-30h ) and maximum serum IG concentration (Cins.max ). Primary PD endpoints were area under the GIR-time curve from 0 to 30 hours (AUCGIR0-30h ) and maximum GIR (GIRmax ). RESULTS Bioequivalence among MYL-1501D, US IG and EU IG was demonstrated for the primary PK and PD endpoints. Least squares mean ratios were close to 1, and 90% confidence intervals were within 0.80 to 1.25. The PD GIR-time profiles were nearly superimposable. There were no noticeable differences in the safety profiles of the three treatments, and no serious adverse events were reported. CONCLUSIONS Equivalence with regard to PK and PD characteristics was shown among MYL-1501D, US IG and EU IG in patients with T1DM, and each treatment was well tolerated and safe.

中文翻译：

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拟议的生物仿制药 MYL-1501D 与美国和欧洲甘精胰岛素制剂在 1 型糖尿病患者中的药代动力学和药效学生物等效性。


目的 报告比较 MYL-1501D、美国参比甘精胰岛素 (US IG) 和欧洲参比甘精胰岛素 (EU IG) 的 1 期生物等效性结果。材料和方法 双盲、随机、三向交叉研究比较了 MYL-1501D、US IG 和 EU IG 的药代动力学 (PK) 和药效 (PD) 特征。总共有 114 名 1 型糖尿病 (T1DM) 患者在自动血糖钳夹条件下接受了 0.4 U/kg 的每种研究治疗。在 30 小时内评估胰岛素代谢物 M1 浓度、甘精胰岛素 (IG) 和葡萄糖输注速率 (GIR)。主要PK终点是0至30小时的血清IG浓度-时间曲线下面积(AUCins.0-30h)和最大血清IG浓度(Cins.max)。主要 PD 终点是 0 至 30 小时的 GIR 时间曲线下面积 (AUCGIR0-30h ) 和最大 GIR (GIRmax )。结果 MYL-1501D、US IG 和 EU IG 之间的主要 PK 和 PD 终点的生物等效性得到证实。最小二乘均值比率接近 1，90% 置信区间在 0.80 至 1.25 范围内。 PD GIR 时间曲线几乎是可叠加的。三种治疗方法的安全性没有明显差异，也没有报告严重不良事件。结论 MYL-1501D、US IG 和 EU IG 在 T1DM 患者中显示出 PK 和 PD 特征的等效性，并且每种治疗均具有良好的耐受性和安全性。