Xiao-Xue Zhu1, Da-Long Zhu2, Xiao-Ying Li3, Ya-Lin Li4, Xiao-Wei Jin4, Tian-Xin Hu4, Yu Zhao4, Yong-Guo Li4, Gui-Yu Zhao4, Shuang Ren4, Yi Zhang4, Yan-Hua Ding1, Li Chen4. 1. Phase I Clinical Trial Unit, The First Hospital of Jilin University, Changchun, China. 2. Department of Endocrinology and Metabolism, Nanjing Drum Hospital, Nanjing University Medical School, Nanjing, China. 3. Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China. 4. Hua Medicine (Shanghai) Limited, Shanghai, China.
Abstract
AIMS: To investigate the pharmacokinetics and pharmacodynamics of a dual-acting glucokinase activator, dorzagliatin, and its safety, tolerability and effect on pancreatic β-cell function in Chinese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: A total of 24 T2D patients were selected, utilizing a set of predefined clinical biomarkers, and were randomized to receive dorzagliatin 75 mg twice or once daily (BID, QD respectively) for 28 days. Changes in HbA1c and glycaemic parameters from baseline to Day 28 were assessed. In addition, changes in β-cell function from baseline to Day 32 were evaluated. RESULTS: Significant reductions in HbA1c were observed in both regimens on Day 28 (-0.79%, 75 mg BID; -1.22%, 75 mg QD). Similar trends were found in the following parameters, including reductions from baseline in fasting plasma glucose by 1.20 mmol/L and 1.51 mmol/L, in 2-hour postprandial glucose by 2.48 mmol/L and 5.03 mmol/L, and in glucose AUC0-24 by 18.59% and 20.98%, for the BID and QD groups, respectively. Both regimens resulted in improvement in β-cell function as measured by steady state HOMA 2 parameter, %B, which increased by 36.31% and 40.59%, and by dynamic state parameter, ΔC30 /ΔG30 , which increased by 24.66% and 167.67%, for the BID and QD groups, respectively. Dorzagliatin was well tolerated in both regimens, with good pharmacokinetic profiles. CONCLUSIONS:Dorzagliatin treatment for 28 days in Chinese T2D patients, selected according to predefined biomarkers, resulted in significant improvement in β-cell function and glycaemic control. The safety and pharmacokinetic profile of dorzagliatin supports a subsequent Phase II trial design and continued clinical development.
RCT Entities:
AIMS: To investigate the pharmacokinetics and pharmacodynamics of a dual-acting glucokinase activator, dorzagliatin, and its safety, tolerability and effect on pancreatic β-cell function in Chinese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: A total of 24 T2D patients were selected, utilizing a set of predefined clinical biomarkers, and were randomized to receive dorzagliatin 75 mg twice or once daily (BID, QD respectively) for 28 days. Changes in HbA1c and glycaemic parameters from baseline to Day 28 were assessed. In addition, changes in β-cell function from baseline to Day 32 were evaluated. RESULTS: Significant reductions in HbA1c were observed in both regimens on Day 28 (-0.79%, 75 mg BID; -1.22%, 75 mg QD). Similar trends were found in the following parameters, including reductions from baseline in fasting plasma glucose by 1.20 mmol/L and 1.51 mmol/L, in 2-hour postprandial glucose by 2.48 mmol/L and 5.03 mmol/L, and in glucose AUC0-24 by 18.59% and 20.98%, for the BID and QD groups, respectively. Both regimens resulted in improvement in β-cell function as measured by steady state HOMA 2 parameter, %B, which increased by 36.31% and 40.59%, and by dynamic state parameter, ΔC30 /ΔG30 , which increased by 24.66% and 167.67%, for the BID and QD groups, respectively. Dorzagliatin was well tolerated in both regimens, with good pharmacokinetic profiles. CONCLUSIONS:Dorzagliatin treatment for 28 days in Chinese T2D patients, selected according to predefined biomarkers, resulted in significant improvement in β-cell function and glycaemic control. The safety and pharmacokinetic profile of dorzagliatin supports a subsequent Phase II trial design and continued clinical development.
Authors: Konstantinos A Toulis; Krishnarajah Nirantharakumar; Chrysa Pourzitaki; Anthony H Barnett; Abd A Tahrani Journal: Drugs Date: 2020-04 Impact factor: 9.546