PDF(Pubmed)
Abstract：
BACKGROUND: The Chinese Diabetes Society recommends basal insulin and glucagon-like peptide-1 receptor agonists as an add-on therapy to first-line oral antihyperglycemic drugs for people with type 2 diabetes (T2D). Fixed-ratio combination of insulin glargine 100 U/ml (iGlar) and lixisenatide (iGlarLixi) is known to improve glycemic control in adults with T2D. However, the pharmacokinetics of iGlarLixi has not been evaluated in Chinese participants. The present study evaluated pharmacokinetics and safety of two iGlarLixi (10 U/10 μg and 30 U/15 μg) doses following single subcutaneous administration in healthy Chinese participants.
METHODS: This was a Phase 1, single-center, open-label, parallel-group, randomized study in healthy Chinese adults who were randomized to receive a single dose of iGlarLixi with either 1:1 (10 U/10 μg) or 2:1 (30 U/15 μg) ratio of iGlar and lixisenatide. Primary objectives include assessment of pharmacokinetics of iGlar in iGlarLixi 30 U/15 μg group and the pharmacokinetics of lixisenatide in both the groups (iGlarLixi 10 U/10 μg and iGlarLixi 30 U/15 μg). Safety and tolerability were also assessed.
RESULTS: In iGlarLixi 30 U/15 μg group, iGlar concentrations were low and quantifiable in three of ten participants, while its main metabolite (M1) was quantifiable in all participants, reflecting rapid conversion of iGlar to M1. Median INS-tmax was 14.00 h for iGlar and 13.00 h post-dose for M1. Absorption of lixisenatide was similar in both dose groups with median tmax of 3.25 and 2.00 h post-dose in both groups. The exposure increase was dose proportionate with a 1.5-fold increase in the lixisenatide dose. Adverse events observed were consistent with those previously reported with iGlar or lixisenatide.
CONCLUSIONS: iGlarLixi administration resulted in early absorption of both iGlar and lixisenatide with a good tolerability profile in healthy Chinese participants. These results are consistent with the previously published data from other geographic regions.
BACKGROUND: U1111-1194-9411.
METHODS: This was a Phase 1, single-center, open-label, parallel-group, randomized study in healthy Chinese adults who were randomized to receive a single dose of iGlarLixi with either 1:1 (10 U/10 μg) or 2:1 (30 U/15 μg) ratio of iGlar and lixisenatide. Primary objectives include assessment of pharmacokinetics of iGlar in iGlarLixi 30 U/15 μg group and the pharmacokinetics of lixisenatide in both the groups (iGlarLixi 10 U/10 μg and iGlarLixi 30 U/15 μg). Safety and tolerability were also assessed.
RESULTS: In iGlarLixi 30 U/15 μg group, iGlar concentrations were low and quantifiable in three of ten participants, while its main metabolite (M1) was quantifiable in all participants, reflecting rapid conversion of iGlar to M1. Median INS-tmax was 14.00 h for iGlar and 13.00 h post-dose for M1. Absorption of lixisenatide was similar in both dose groups with median tmax of 3.25 and 2.00 h post-dose in both groups. The exposure increase was dose proportionate with a 1.5-fold increase in the lixisenatide dose. Adverse events observed were consistent with those previously reported with iGlar or lixisenatide.
CONCLUSIONS: iGlarLixi administration resulted in early absorption of both iGlar and lixisenatide with a good tolerability profile in healthy Chinese participants. These results are consistent with the previously published data from other geographic regions.
BACKGROUND: U1111-1194-9411.
摘要：
背景：中国糖尿病学会推荐基础胰岛素和胰高血糖素样肽-1受体激动剂作为2型糖尿病（T2D）患者一线口服降糖药的附加治疗。已知甘精胰岛素100U/ml（iGlar）和利西拉来（iGlarLixi）的固定比例组合可改善T2D成人的血糖控制。然而,iGlarLixi的药代动力学尚未在中国参与者中进行评估.本研究评估了健康中国参与者单次皮下给药后两种iGlarLixi（10U/10μg和30U/15μg）剂量的药代动力学和安全性。
方法：这是第一阶段，单中心，开放标签，平行组，在健康的中国成年人中进行随机研究，这些成年人被随机分配接受1：1（10U/10μg）或2：1（30U/15μg）比例的iGlar和利西拉来单剂量iGlarLixi。主要目标包括评估iGlarLixi30U/15μg组中iGlar的药代动力学和两组中利西拉来的药代动力学（iGlarLixi10U/10μg和iGlarLixi30U/15μg）。还评估了安全性和耐受性。
结果：在iGlarLixi30U/15μg组中，十个参与者中有三个人的iGlar浓度较低且可量化，虽然它的主要代谢物(M1)在所有参与者中都是可量化的，反映iGlar到M1的快速转换。iGlar的INS-tmax中位数为14.00h，M1的给药后为13.00h。利西拉来的吸收在两个剂量组中相似,在两个组中,中位tmax为3.25和给药后2.00小时。暴露增加与利西拉来剂量增加1.5倍成比例。观察到的不良事件与以前报道的iGlar或利西拉来的不良事件一致。
结论：iGlarLixi给药导致iGlar和利西拉来在健康中国参与者中早期吸收，具有良好的耐受性。这些结果与以前发布的其他地理区域的数据一致。
背景：U1111-1194-9411。
方法：这是第一阶段，单中心，开放标签，平行组，在健康的中国成年人中进行随机研究，这些成年人被随机分配接受1：1（10U/10μg）或2：1（30U/15μg）比例的iGlar和利西拉来单剂量iGlarLixi。主要目标包括评估iGlarLixi30U/15μg组中iGlar的药代动力学和两组中利西拉来的药代动力学（iGlarLixi10U/10μg和iGlarLixi30U/15μg）。还评估了安全性和耐受性。
结果：在iGlarLixi30U/15μg组中，十个参与者中有三个人的iGlar浓度较低且可量化，虽然它的主要代谢物(M1)在所有参与者中都是可量化的，反映iGlar到M1的快速转换。iGlar的INS-tmax中位数为14.00h，M1的给药后为13.00h。利西拉来的吸收在两个剂量组中相似,在两个组中,中位tmax为3.25和给药后2.00小时。暴露增加与利西拉来剂量增加1.5倍成比例。观察到的不良事件与以前报道的iGlar或利西拉来的不良事件一致。
结论：iGlarLixi给药导致iGlar和利西拉来在健康中国参与者中早期吸收，具有良好的耐受性。这些结果与以前发布的其他地理区域的数据一致。
背景：U1111-1194-9411。
