目的:我们评估了药代动力学,安全,在健康的西方和韩国参与者中,达格列净/西格列汀固定剂量组合(FDC)与单组分(IC)片剂的耐受性。这些抗高血糖药物的组合提供了有效的血糖控制,FDC的使用通常被证明可以改善2型糖尿病(T2DM)患者的用药依从性.
方法:两个随机,开放标签,两期,两种治疗,单剂量,单中心,纳入了对健康禁食的德国参与者(年龄18~55岁;西方研究)和韩国参与者(年龄19~55岁;韩国研究)进行的交叉生物等效性研究.在两项研究中,药代动力学参数(最大[峰值]血浆浓度[Cmax],从零到最后一个可量化浓度[AUClast]的血浆浓度-时间曲线下面积,和从零到无穷大的血浆浓度-时间曲线下面积[AUCinf])用于评估10mg达格列净/100mg西格列汀FDC(治疗A)与其IC(治疗B)在禁食条件下的生物等效性。在整个研究中评估安全性和耐受性。
结果:46名健康参与者(男性,60.9%;平均年龄,39.5岁;平均体重指数[BMI],23.9kg/m2)在西方研究中随机分组,和51名健康参与者(男性,100.0%;平均年龄,24.6年;平均BMI,23.9kg/m2)在韩国研究中随机分配。在两项研究中,参与者以1:1随机分为治疗序列AB和治疗序列BA.在西方和韩国研究中,达格列净/西格列汀FDC与IC片剂生物等效,因为达格列净和西格列汀的药代动力学参数的几何最小二乘平均值的FDC与IC比值的90%置信区间均在0.8000~1.2500生物等效性标准界限内.观察到的药代动力学参数差异,比如Cmax,AUClast,AUCinf,西方和韩国的研究没有临床意义.达格列净/西格列汀FDC及其IC耐受性良好,在任何研究人群中均未报告严重不良事件。
结论:10mg达格列净/100mg西格列汀FDC和IC制剂在禁食的西方和韩国健康参与者中具有生物等效性,没有发现新的安全问题,因此,为目前接受单独药物作为治疗方案一部分的患者提供了一种有用的替代方案。
背景:西方研究(clinicaltrials.gov:NCT05266404)和韩国研究(clinicaltrials.gov:NCT05453786)。
OBJECTIVE: We evaluated the pharmacokinetics, safety, and tolerability of a fixed-dose combination (FDC) of dapagliflozin/sitagliptin versus individual component (IC) tablets in healthy Western and Korean participants. The combination of these antihyperglycemic drugs provides efficient glucose control, and the use of FDC has generally been shown to improve medication adherence in individuals with type 2 diabetes mellitus (T2DM).
METHODS: Two randomized, open-label, two-period, two-treatment, single-dose, single-center, crossover bioequivalence studies conducted on healthy fasted German participants (aged 18-55 years; Western study) and South Korean participants (aged 19-55 years; Korean study) were included. In both studies, pharmacokinetic parameters (maximum [peak] plasma concentration [Cmax], area under the plasma concentration-time curve from zero to the last quantifiable concentration [AUClast], and area under the plasma concentration-time curve from zero to infinity [AUCinf]) were used to assess the bioequivalence of 10 mg dapagliflozin/100 mg sitagliptin FDC (Treatment A) with their ICs (Treatment B) under fasted conditions. Safety and tolerability were assessed throughout the study.
RESULTS: Forty-six healthy participants (male, 60.9%; mean age, 39.5 years; mean body mass index [BMI], 23.9 kg/m2) were randomized in the Western study, and 51 healthy participants (male, 100.0%; mean age, 24.6 years; mean BMI, 23.9 kg/m2) were randomized in the Korean study. In both studies, the participants were randomized 1:1 into treatment sequence AB and treatment sequence BA. Dapagliflozin/sitagliptin FDC was bioequivalent to IC tablets in both Western and Korean studies, as the 90% confidence interval of the FDC to IC ratios of the geometric least-squares means of the pharmacokinetic parameters for both dapagliflozin and sitagliptin was within the 0.8000-1.2500 bioequivalence criterion limit. The observed differences in pharmacokinetic parameters, such as Cmax, AUClast, and AUCinf, between the Western and Korean studies were not clinically meaningful. Dapagliflozin/sitagliptin FDC and their ICs were well tolerated, with no serious adverse events reported in any of the study populations.
CONCLUSIONS: The 10 mg dapagliflozin/100 mg sitagliptin FDC and IC formulations were bioequivalent in fasted healthy Western and Korean participants, with no new safety concerns identified, thus offering a useful alternative for patients currently receiving individual medications as part of their treatment regimen.
BACKGROUND: Western study (clinicaltrials.gov: NCT05266404) and Korean study (clinicaltrials.gov: NCT05453786).