Clinical trial NCT05146869: A Single-dose and Multiple-dose Study to Evaluate the Pharmacokinetics and Pharmacodynamics of DBPR108 Tablets in Type 2 Diabetes Mellitus Patients
Official title: A Randomized, Open-Label, Parallel-Cohort, Single-dose and Multiple-dose Phase I Study of DBPR108 Tablets in Type 2 Diabetes Mellitus Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-12-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Peak plasma concentration (Cmax) of DBPR108 tablets
timeFrame: Day 1-Day 11
measure: Area under the plasma concentration versus time curve (AUC) of DBPR108 tablets in plasma
timeFrame: Day 1-Day 11
measure: Half-life(t1/2) of DBPR108 tablets
timeFrame: Day 1-Day 11
measure: Apparent volume of Distribution(Vz/F)of DBPR108 tablets
timeFrame: Day 1-Day 11
measure: CL/F of DBPR108 tablets
timeFrame: Day 1-Day 11
measure: Change from baseline in dipeptidyl peptidase-IV inhibition rate
timeFrame: Day 1-Day 11
measure: Change from baseline in active glucagon-like peptide1 concentration
timeFrame: Day 1-Day 11
Secondary outcomes:
measure: The number of patients with adverse events
timeFrame: Throughout the study period, with an average of 1 months
measure: Clinically significant changes from baseline in 12-lead electrocardiogram (ECG) examination will be recorded as AEs at each visit time point
timeFrame: Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11).
measure: Clinically significant changes from baseline in vital signs examination will be recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 1 months
measure: Clinically significant changes from baseline in vital signs examination will be recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 1 months
measure: Clinically significant changes from baseline in vital signs examination will be recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 1 months
measure: Clinically significant changes from baseline in physical examination will be recorded as AEs at each visit time point.
timeFrame: Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11).
measure: Clinically significant changes from baseline in routine blood test will be recorded as AEs at each visit time point.
timeFrame: Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11)
measure: 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.
timeFrame: Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11)
measure: 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.
timeFrame: Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11)
measure: 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.
timeFrame: Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11)
measure: 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.
timeFrame: Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day 11)
measure: Clinically significant changes from baseline in routine urine test will be recorded as AEs at each visit time point.
timeFrame: Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11)
measure: Clinically significant changes from baseline in routine urine test will be recorded as AEs at each visit time point.
timeFrame: Within screening period (Day-21 to Day-15), baseline period (Day-7 to Day-1), and before discharge (Day11)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Anzhen Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Anzhen Hospital of Capital Medical University , Beijing, China
name: Yang Lin, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Anzhen Hospital of Capital Medical University , Beijing, China
name: Shan NA Jing, PhD
role: PRINCIPAL_INVESTIGATOR
References: