A Phase 1 Multiple Dose Study of Tirzepatide in Chinese Patients with Type 2 Diabetes

被引:11
作者
Feng, Ping [1 ,2 ]
Sheng, Xiaoyan [3 ]
Ji, Yongjia [4 ]
Urva, Shweta [5 ]
Wang, Feng [4 ]
Miller, Sheila [5 ]
Qian, Chenxi [4 ]
An, Zhenmei [6 ]
Cui, Yimin [3 ,7 ]
机构
[1] Sichuan Univ, West China Hosp, Dept Pharm, 37 Guoxue Lane, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, West China Hosp, Clin Trial Ctr, 37 Guoxue Lane, Chengdu 610041, Sichuan, Peoples R China
[3] Peking Univ First Hosp, Dept Pharm, 8 Xishiku St, Beijing 100034, Peoples R China
[4] Eli Lilly & Co, 19F Ctr T1 HKRI Taikoo 288 Shimen 1 Rd, Shanghai 200041, Peoples R China
[5] Eli Lilly & Co, Lilly Corp Ctr, 893 Delaware St, Indianapolis, IN 46285 USA
[6] Sichuan Univ, West China Hosp, Dept Endocrinol & Metab, 37 Guoxue Lane, Chengdu 610041, Sichuan, Peoples R China
[7] Peking Univ First Hosp, Inst Clin Pharmacol, Xueyuan Rd 38, Beijing 100191, Peoples R China
关键词
GIP; GLP-1; Phase; 1; Pharmacodynamics; Pharmacokinetics; Tirzepatide; Type; 2; diabetes; GLP-1 RECEPTOR AGONIST; DUAL GIP;
D O I
10.1007/s12325-023-02536-8
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
IntroductionTo investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of tirzepatide in Chinese patients with type 2 diabetes (T2D).MethodsIn 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.ResultsTwenty-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.ConclusionsTirzepatide 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.
引用
收藏
页码:3434 / 3445
页数:12
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