A Randomized, Open-Label, Parallel-Cohort, Single-dose and Multiple-dose Phase I Study of DBPR108 Tablets in Type 2 Diabetes Mellitus Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Peak plasma concentration (Cmax) of DBPR108 tablets
研究概览
简要总结
This is a phase I study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single-dose and multiple-dose of DBPR108 tablets in Type 2 Diabetes Mellitus Patients.
详细描述
This study aims to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics characteristics, single-dose and multiple-dose of DBPR108 tablets in Chinese Type 2 Diabetes Mellitus Patients. The 30 eligible patients will be randomized to receive 50 mg, 100 mg, or 200 mg DBPR108 tablets.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who meet the World Health Organization (WHO) (1999) criteria for the diagnosis and classification criteria for type 2 diabetes mellitus;
- •18 ≤ age ≤ 75 years old, male or female;
- •Body mass index (BMI) within the range of 19-35 kg/m^2 (inclusive), BMI = weight (kg) / height^2 (m^2);
- •7.0% ≤Hemoglobin A1c (HbA1c) ≤ 9.5%;
- •Patients who voluntarily participate in the study and sign the informed consent form;
- •Patients who agree to use contraception from the signing of the informed consent form until 1 month after the end of the last medication.
排除标准
- •Fasting plasma glucose (FPG) > 13.9 mmol/L;
- •The investigator determines that the patients need to use insulin therapy;
- •Patients with acute or serious complications of diabetes (including diabetic ketoacidosis, hyperosmotic nonketotic diabetic coma, lactic acidosis and hypoglycemia coma);
- •History of severe hypoglycemia (hypoglycemia with severe cognitive impairment and requiring other measures to help recover);
- •History of acute or chronic pancreatitis, or related diseases that are most common cause of acute pancreatitis (such as recurrent cholelithiasis, etc.);
- •History of allergy to DPP-4 inhibitors or the investigator determines that the patients may be allergic to investigational drug;
- •Patients with untreated hyperthyroidism and other diseases, which may affect blood glucose;
- •Patients who have used other hypoglycemic drugs within 14 days before the first dose; or patients who are not suitable for this study as determined by the investigator due to taking other hypoglycemic drugs;
- •Patients with inflammatory bowel disease, partial intestinal obstruction or chronic bowel disease related to obvious digestive and absorption disorders;
- •Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 3 * upper limit of normal (ULN), or total bilirubin > 1.5 *ULN;
- •Abnormal renal function: serum creatinine>1.5 * ULN; or eGFR< 45 mL/min/1.73m^2;
- •White blood cells (WBC) < 3.0 *10^9/L and neutrophil count of peripheral blood < 1.5 * 10^9/L; hemoglobin < 100 g / L; triglyceride > 5.7 mmol/L;
- •Patients who have the second or third degree atrioventricular block, long Q-T syndrome, or QTc>500 ms without cardiac pacemaker;
- •Patients with any one of HBsAg, hepatitis C antibody, anti-HIV antibody and antibody of treponema pallidum positive;
- •Female patients of childbearing age with pregnant test positive or lactating women;
- •History of alcohol or drug abuse within 3 months before screening, alcohol abuse is average alcohol intake more than 14 units alcohol (1 unit=12 ounces or 360 mL of beer,1.5 ounces or 45 mL spirits with 40% alc/vol, 5 ounces or 150 mL grape wine); or intake any other products containing alcohol within 2 days before the first administration of investigational product;
- •Patients who smoke more than 5 cigarettes per day within 3 months prior to screening;
- •Patients with consumption of grapefruit juice, methylxanthine-rich food or beverage (such as coffee, tea, cola, chocolate, energy drinks) within 2 days before the first administration in treatment period , or patients who have strenuous exercise, or have other factors affecting drug absorption, distribution, metabolism, excretion, etc;
- •Participation in other clinical trials or administration of any other investigational drugs or devices within 3 months before screening;
- •Patients with the following diseases:
- •Serious dysrhythmias, obvious left ventricular dysfunction, New York Heart Association (NYHA) functional class III or IV;
- •History of unstable angina pectoris, myocardial infarction, or other high-risk coronary artery diseases;
- •Uncontrolled hypertension, systolic pressure ≥160 mmHg or diastolic pressure ≥100 mmHg;
- •History of cancer , organ transplantation;
- •History of epilepsy, psychosis, severe depression, etc.
- •Not suitable for this study as determined by the investigator due to other reasons.
研究组 & 干预措施
50 mg DBPR108 tablets
10 patients will be randomized to receive 50 mg DBPR108 tablets.
干预措施: DBPR108 tablets (Drug)
100 mg DBPR108 tablets
10 patients will be randomized to receive 100 mg DBPR108 tablets.
干预措施: DBPR108 tablets (Drug)
200 mg DBPR108 tablets
10 patients will be randomized to receive 200 mg DBPR108 tablets.
干预措施: DBPR108 tablets (Drug)
结局指标
主要结局
Peak plasma concentration (Cmax) of DBPR108 tablets
时间窗: Day 1-Day 11
Cmax of DBPR108 tablets will be assessed after single-dose and multiple-dose administration
Apparent volume of Distribution(Vz/F)of DBPR108 tablets
时间窗: Day 1-Day 11
Vz/F of DBPR108 tablets will be assessed after single-dose and multiple-dose administration
Area under the plasma concentration versus time curve (AUC) of DBPR108 tablets in plasma
时间窗: Day 1-Day 11
AUC of DBPR108 tablets will be assessed after single-dose and multiple-dose administration
CL/F of DBPR108 tablets
时间窗: Day 1-Day 11
Apparent clearance(CL/F) of DBPR108 tablets will be assessed single-dose and multiple-dose administration
Half-life(t1/2) of DBPR108 tablets
时间窗: Day 1-Day 11
T1/2 of DBPR108 tablets will be assessed after single-dose and multiple-dose administration
Change from baseline in dipeptidyl peptidase-IV inhibition rate
时间窗: Day 1-Day 11
Change from baseline in dipeptidyl peptidase-IV inhibition rate will be assessed after single-dose and multiple-dose administration
Change from baseline in active glucagon-like peptide1 concentration
时间窗: Day 1-Day 11
Change from baseline in active glucagon-like peptide1 concentration will be assessed after single-dose and multiple-dose administration
次要结局
- Clinically significant changes from baseline in vital signs examination will be recorded as AEs at each visit time point.(Throughout the study period, with an average of 1 months)
- Clinically significant changes from baseline in blood biochemistry test will be recorded as AEs at each visit time point.recorded as AEs at each visit time point.(Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day 11))
- Clinically significant changes from baseline in routine urine test will be recorded as AEs at each visit time point.(Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11))
- The number of patients with adverse events(Throughout the study period, with an average of 1 months)
- Clinically significant changes from baseline in 12-lead electrocardiogram (ECG) examination will be recorded as AEs at each visit time point(Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11).)
- Clinically significant changes from baseline in physical examination will be recorded as AEs at each visit time point.(Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11).)
- Clinically significant changes from baseline in routine blood test will be recorded as AEs at each visit time point.(Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11))