A Single-dose and Multiple-dose Study to Evaluate the Pharmacokinetics and Pharmacodynamics of DBPR108 Tablets in Type 2 Diabetes Mellitus Patients

A Randomized, Open-Label, Parallel-Cohort, Single-dose and Multiple-dose Phase I Study of DBPR108 Tablets in Type 2 Diabetes Mellitus Patients

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.

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.

Inclusion Criteria:

1. Patients who meet the World Health Organization (WHO) (1999) criteria for the diagnosis and classification criteria for type 2 diabetes mellitus;
2. 18 ≤ age ≤ 75 years old, male or female;
3. Body mass index (BMI) within the range of 19-35 kg/m^2 (inclusive), BMI = weight (kg) / height^2 (m^2);
4. 7.0% ≤Hemoglobin A1c (HbA1c) ≤ 9.5%;
5. Patients who voluntarily participate in the study and sign the informed consent form;
6. Patients who agree to use contraception from the signing of the informed consent form until 1 month after the end of the last medication.

Exclusion Criteria:

1. Fasting plasma glucose (FPG) > 13.9 mmol/L;

2. The investigator determines that the patients need to use insulin therapy;

3. Patients with acute or serious complications of diabetes (including diabetic ketoacidosis, hyperosmotic nonketotic diabetic coma, lactic acidosis and hypoglycemia coma);

4. History of severe hypoglycemia (hypoglycemia with severe cognitive impairment and requiring other measures to help recover);

5. History of acute or chronic pancreatitis, or related diseases that are most common cause of acute pancreatitis (such as recurrent cholelithiasis, etc.);

6. History of allergy to DPP-4 inhibitors or the investigator determines that the patients may be allergic to investigational drug;

7. Patients with untreated hyperthyroidism and other diseases, which may affect blood glucose;

8. 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;

9. Patients with inflammatory bowel disease, partial intestinal obstruction or chronic bowel disease related to obvious digestive and absorption disorders;

10. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 3 * upper limit of normal (ULN), or total bilirubin > 1.5 *ULN;

11. Abnormal renal function: serum creatinine>1.5 * ULN; or eGFR< 45 mL/min/1.73m^2;

12. 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;

13. Patients who have the second or third degree atrioventricular block, long Q-T syndrome, or QTc>500 ms without cardiac pacemaker;

14. Patients with any one of HBsAg, hepatitis C antibody, anti-HIV antibody and antibody of treponema pallidum positive;

15. Female patients of childbearing age with pregnant test positive or lactating women;

16. 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;

17. Patients who smoke more than 5 cigarettes per day within 3 months prior to screening;

18. 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;

19. Participation in other clinical trials or administration of any other investigational drugs or devices within 3 months before screening;

20. Patients with the following diseases:

    1. Serious dysrhythmias, obvious left ventricular dysfunction, New York Heart Association (NYHA) functional class III or IV;
    2. History of unstable angina pectoris, myocardial infarction, or other high-risk coronary artery diseases;
    3. Uncontrolled hypertension, systolic pressure ≥160 mmHg or diastolic pressure ≥100 mmHg;
    4. History of cancer , organ transplantation;
    5. History of epilepsy, psychosis, severe depression, etc.

21. Not suitable for this study as determined by the investigator due to other reasons.