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Abstract：
To investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of tirzepatide in Chinese patients with type 2 diabetes (T2D).
In this phase 1, double-blind, placebo-controlled, multiple dose study, patients were randomized into one of two cohorts to receive once-weekly subcutaneous tirzepatide or placebo. The initial tirzepatide dose in both cohorts was 2.5 mg, which was increased by 2.5 mg every 4 weeks to a maximum final dose of 10.0 mg at week 16 (Cohort 1) or 15.0 mg at week 24 (Cohort 2). The primary outcome was the safety and tolerability of tirzepatide.
Twenty-four patients were randomized (tirzepatide 2.5-10.0 mg: n = 10, tirzepatide 2.5-15.0 mg: n = 10, placebo: n = 4); 22 completed the study. The most frequently reported treatment-emergent adverse events (TEAEs) among patients receiving tirzepatide were diarrhea and decreased appetite; most TEAEs were mild and resolved spontaneously with no serious adverse events reported in the tirzepatide groups and one in the placebo group. The plasma concentration half-life of tirzepatide was approximately 5-6 days. Mean glycated hemoglobin (HbA1c) decreased over time from baseline in the 2.5-10.0 mg (- 2.4%) and 2.5-15.0 mg (- 1.6%) tirzepatide groups, at week 16 and week 24, respectively, but remained steady in patients receiving placebo. Body weight decreased from baseline by - 4.2 kg at week 16 in the tirzepatide 2.5-10.0 mg group and by - 6.7 kg at week 24 in the 2.5-15.0 mg group. Mean fasting plasma glucose levels fell from baseline by - 4.6 mmol/L in the tirzepatide 2.5-10.0 mg group at week 16 and by - 3.7 mmol/L at week 24 in the tirzepatide 2.5-15.0 mg group.
Tirzepatide was well tolerated in this population of Chinese patients with T2D. The safety, tolerability, PK, and PD profile of tirzepatide support once-weekly dosing in this population.
ClinicalTrials.gov: NCT04235959.
In this phase 1, double-blind, placebo-controlled, multiple dose study, patients were randomized into one of two cohorts to receive once-weekly subcutaneous tirzepatide or placebo. The initial tirzepatide dose in both cohorts was 2.5 mg, which was increased by 2.5 mg every 4 weeks to a maximum final dose of 10.0 mg at week 16 (Cohort 1) or 15.0 mg at week 24 (Cohort 2). The primary outcome was the safety and tolerability of tirzepatide.
Twenty-four patients were randomized (tirzepatide 2.5-10.0 mg: n = 10, tirzepatide 2.5-15.0 mg: n = 10, placebo: n = 4); 22 completed the study. The most frequently reported treatment-emergent adverse events (TEAEs) among patients receiving tirzepatide were diarrhea and decreased appetite; most TEAEs were mild and resolved spontaneously with no serious adverse events reported in the tirzepatide groups and one in the placebo group. The plasma concentration half-life of tirzepatide was approximately 5-6 days. Mean glycated hemoglobin (HbA1c) decreased over time from baseline in the 2.5-10.0 mg (- 2.4%) and 2.5-15.0 mg (- 1.6%) tirzepatide groups, at week 16 and week 24, respectively, but remained steady in patients receiving placebo. Body weight decreased from baseline by - 4.2 kg at week 16 in the tirzepatide 2.5-10.0 mg group and by - 6.7 kg at week 24 in the 2.5-15.0 mg group. Mean fasting plasma glucose levels fell from baseline by - 4.6 mmol/L in the tirzepatide 2.5-10.0 mg group at week 16 and by - 3.7 mmol/L at week 24 in the tirzepatide 2.5-15.0 mg group.
Tirzepatide was well tolerated in this population of Chinese patients with T2D. The safety, tolerability, PK, and PD profile of tirzepatide support once-weekly dosing in this population.
ClinicalTrials.gov: NCT04235959.
摘要：
背景：为了调查安全性，耐受性,药代动力学（PK），中国2型糖尿病（T2D）患者的替瑞沙肽和药效学（PD）。
方法：在此阶段1，双盲，安慰剂对照,多剂量研究，患者被随机分为2个队列中的1个,接受每周一次的替利西帕肽皮下治疗或安慰剂治疗.两组患者的初始剂量为2.5mg，每4周增加2.5mg，至第16周最大终剂量为10.0mg（第1组）或第24周最大终剂量为15.0mg（第2组）。主要结果是替利西帕肽的安全性和耐受性。
结果：24名患者被随机分配（替利平肽2.5-10.0mg：n=10，替利平肽2.5-15.0mg：n=10，安慰剂：n=4）；22名患者完成了研究。在接受替利平治疗的患者中，最常报告的治疗引起的不良事件（TEAE）是腹泻和食欲下降；大多数TEAE是轻度的，可以自发缓解，在替利平治疗组中没有报告严重不良事件，在安慰剂组中没有报告严重不良事件。替拉肽的血浆浓度半衰期约为5-6天。在2.5-10.0mg(-2.4%)和2.5-15.0mg(-1.6%)替拉肽组中,平均糖化血红蛋白(HbA1c)随时间从基线下降,分别在第16周和第24周，但在接受安慰剂的患者中保持稳定。在第16周时，替拉肽2.5-10.0mg组的体重从基线下降-4.2kg，在第24周时，在2.5-15.0mg组的体重从基线下降-6.7kg。在第16周时，替利平肽2.5-10.0mg组的平均空腹血糖水平从基线下降-4.6mmol/L，在第24周时，替利平肽2.5-15.0mg组的平均空腹血糖水平从基线下降-3.7mmol/L。
结论：Tirzepatide在中国T2D患者中具有良好的耐受性。安全,耐受性,PK,在该人群中,替利西帕肽的PD谱支持每周一次给药.
背景：ClinicalTrials.gov：NCT04235959。
方法：在此阶段1，双盲，安慰剂对照,多剂量研究，患者被随机分为2个队列中的1个,接受每周一次的替利西帕肽皮下治疗或安慰剂治疗.两组患者的初始剂量为2.5mg，每4周增加2.5mg，至第16周最大终剂量为10.0mg（第1组）或第24周最大终剂量为15.0mg（第2组）。主要结果是替利西帕肽的安全性和耐受性。
结果：24名患者被随机分配（替利平肽2.5-10.0mg：n=10，替利平肽2.5-15.0mg：n=10，安慰剂：n=4）；22名患者完成了研究。在接受替利平治疗的患者中，最常报告的治疗引起的不良事件（TEAE）是腹泻和食欲下降；大多数TEAE是轻度的，可以自发缓解，在替利平治疗组中没有报告严重不良事件，在安慰剂组中没有报告严重不良事件。替拉肽的血浆浓度半衰期约为5-6天。在2.5-10.0mg(-2.4%)和2.5-15.0mg(-1.6%)替拉肽组中,平均糖化血红蛋白(HbA1c)随时间从基线下降,分别在第16周和第24周，但在接受安慰剂的患者中保持稳定。在第16周时，替拉肽2.5-10.0mg组的体重从基线下降-4.2kg，在第24周时，在2.5-15.0mg组的体重从基线下降-6.7kg。在第16周时，替利平肽2.5-10.0mg组的平均空腹血糖水平从基线下降-4.6mmol/L，在第24周时，替利平肽2.5-15.0mg组的平均空腹血糖水平从基线下降-3.7mmol/L。
结论：Tirzepatide在中国T2D患者中具有良好的耐受性。安全,耐受性,PK,在该人群中,替利西帕肽的PD谱支持每周一次给药.
背景：ClinicalTrials.gov：NCT04235959。
