A Phase 1, Open-Label, Sequential, Multiple-Dose, Drug-Drug Interaction Study of Dorzagliatin and Empagliflozin in Subjects with Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- GMR for Cmax of empagliflozin
研究概览
简要总结
This is a Phase 1, open-label, sequential, multiple-dose, drug interaction study of glucokinase activator dorzagliatin and empagliflozin in subjects with T2DM. Pharmacokinetics and pharmacodynamics when dorzagliatin and empagliflozin given alone and in combination will be studied.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects diagnosed with T2DM within at least 3 months prior to screening
- •Male and/or female subjects between the ages of 30 and 65 years, inclusive;
- •Body Mass Index (BMI) of 19 to 38 kg/m2, inclusive, at screening;
- •Fasting C-peptide test result >0.3 nmol/L (>0.90 ng/mL);
- •HbA1c ≥7% and ≤10.5%;
排除标准
- •Fasting blood glucose at screening or Day -1 ≤110 or ≥270 mg/dL ;
- •Type 1 diabetes mellitus;
- •Reported incidence of severe hypoglycemia within 3 months prior to screening;
- •Known contraindications to empagliflozin;
- •Clinically significant gastrointestinal disorder;
- •History or symptoms of clinically significant cardiovascular disease;
- •History of more than three urinary tract infections and/or more than three genital fungal infections in the last 12 months;
- •Reported history of clinically significant central nervous system disease including within one year prior to screening;
- •Reported history of liver disease;
- •Reported history of clinically significant renal disease;
- •Estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73m2;
- •Acute or chronic metabolic acidosis, including diabetic ketoacidosis;
- •Known or suspected malignancy;
- •Any reported hypersensitivity or intolerance to empagliflozin;
- •Antidiabetic treatment with insulin, sulfonylureas, thiazolidinediones or GLP-1 agonist within 3 months prior to screening;
- •Systolic blood pressure <90 or >160 mmHg or diastolic blood pressure <60 or >100 mmHg at screening;
- •A hospital admission or major surgery within 90 days prior to screening;
- •Uncontrolled hypertriglyceridemia >500 mg/dL;
- •Positive blood screen for HIV, HBsAg, or hepatitis C antibody;
- •Positive pregnancy test result;
- •Treated with any investigational drugs within 6 weeks prior to screening;
- •Reported history of prescription drug abuse;
- •Reported history of alcohol abuse
- •Reported history of donation or acute loss of blood during the 90 days prior to screening;
研究组 & 干预措施
Sequential arm ABC
A: Empagliflozin 25 mg QD in the morning on Days 1-5; B: Empagliflozin 25 mg in the morning and Dorzagliatin 75 mg BID (morning and evening) on Days 6-10, with only the morning dose on Day 10; C: Dorzagliatin 75 mg BID (morning and evening) on Days 11-15, with only the morning dose on Day 15.
干预措施: Empagliflozin (Drug)
Sequential arm ABC
A: Empagliflozin 25 mg QD in the morning on Days 1-5; B: Empagliflozin 25 mg in the morning and Dorzagliatin 75 mg BID (morning and evening) on Days 6-10, with only the morning dose on Day 10; C: Dorzagliatin 75 mg BID (morning and evening) on Days 11-15, with only the morning dose on Day 15.
干预措施: Dorzagliatin (Drug)
结局指标
主要结局
GMR for Cmax of empagliflozin
时间窗: up to 10 days
Geometric mean ratio (GMR) between combination and empagliflozin monotherapy for Cmax of empagliflozin
GMR for AUC0-24h of empagliflozin
时间窗: up to 10 days
GMR between combination and empagliflozin in monotherapy for AUC0-24h of empagliflozin
GMR for Cmax of dorzagliatin
时间窗: up to 15 days
GMR between combination and dorzagliatin monotherapy for Cmax of dorzagliatin
GMR for AUC0-24h of dorzagliatin
时间窗: up to 15 days
GMR between combination and dorzagliatin in monotherapy for AUC0-24h of dorzagliatin
Adverse events
时间窗: up to 15 days
Number of participants with AEs
Abnormal vital signs
时间窗: up to 15 days
Number of participants with abnormal vital signs (blood pressure, pulse rate, respiratory rate and oral temperature)
Abnormal clinical laboratory findings
时间窗: up to 15 days
Number of participants with abnormal clinical laboratory findings
12-lead ECG
时间窗: up to 15 days
Number of participants with abnormal ECG VR,, PR, QRS and QT
次要结局
- iCmax of glucose(up to 15 days)
- iAUC0-4h of glucose(up to 15 days)
- iCmax of insulin(up to 15 days)
- iAUC0-4h of insulin(up to 15 days)
- iCmax of C-peptide(up to 15 days)
- iAUC0-4h of C-peptide(up to 15 days)