A Single-dose and Multiple-dose Study to Evaluate the Pharmacokinetics and Pharmacodynamics of DBPR108 Tablets in Type 2 Diabetes Mellitus Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 50 mg DBPR108 tablets 10 patients will be randomized to receive 50 mg DBPR108 tablets. |
Drug: DBPR108 tablets
DBPR108 tablets, oral, once daily on Day 1 and Day 3-9 for a total of 8 doses.
|
| Experimental: 100 mg DBPR108 tablets 10 patients will be randomized to receive 100 mg DBPR108 tablets. |
Drug: DBPR108 tablets
DBPR108 tablets, oral, once daily on Day 1 and Day 3-9 for a total of 8 doses.
|
| Experimental: 200 mg DBPR108 tablets 10 patients will be randomized to receive 200 mg DBPR108 tablets. |
Drug: DBPR108 tablets
DBPR108 tablets, oral, once daily on Day 1 and Day 3-9 for a total of 8 doses.
|
Outcome Measures
Primary Outcome Measures
- Peak plasma concentration (Cmax) of DBPR108 tablets [Day 1-Day 11]
Cmax 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 [Day 1-Day 11]
AUC of DBPR108 tablets will be assessed after single-dose and multiple-dose administration
- Half-life(t1/2) of DBPR108 tablets [Day 1-Day 11]
T1/2 of DBPR108 tablets will be assessed after single-dose and multiple-dose administration
- Apparent volume of Distribution(Vz/F)of DBPR108 tablets [Day 1-Day 11]
Vz/F of DBPR108 tablets will be assessed after single-dose and multiple-dose administration
- CL/F of DBPR108 tablets [Day 1-Day 11]
Apparent clearance(CL/F) of DBPR108 tablets will be assessed single-dose and multiple-dose administration
- Change from baseline in dipeptidyl peptidase-IV inhibition rate [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 [Day 1-Day 11]
Change from baseline in active glucagon-like peptide1 concentration will be assessed after single-dose and multiple-dose administration
Secondary Outcome Measures
- The number of patients with adverse events [Throughout the study period, with an average of 1 months]
The number of patients with adverse events as a measure of safety and tolerability.
- 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).]
ECG monitoring includes P-R, QT and QTc intervals in ms.
- 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]
Vital signs monitoring includes respiratory rate and pulse in times per minute
- 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]
Vital signs monitoring includes systolic blood pressure and diastolic blood pressure in mmHg.
- 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]
Vital signs monitoring includes body temperature in degrees Celsius
- 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).]
Physical examination includes mucocutaneous, lymphonodus, head and neck,chest, abdomen, spinal column, musculoskeletal, nervous system
- 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)]
Routine blood test includes white blood cell count, platelet, neutrophilic granulocyte count, lymphocyte count and monocyte count in 10^9 /L.
- 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 (Day11)]
Blood biochemistry test includes total protein, albumin and albumin in g/L.
- 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 (Day11)]
Blood biochemistry test includes alanine aminotransferase, aspartate aminotransferase, amylase, alkaline phosphatase and in U/L.
- 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 (Day11)]
Blood biochemistry test includes ureophil, glucose, triglyceridein, total cholesterol, high-density lipoprotein, low-density lipoprotein, sodium, potassium, chlorine, calcium in mmol/L
- 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)]
Blood biochemistry test includes total bilirubin and serum creatinine in umol/L.
- 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)]
Routine urine test includes the count of leukocyte, and red blood cell in high-power field.
- 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)]
Routine urine test includes glucose, protein, ketonein in negative or positive.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients who meet the World Health Organization (WHO) (1999) criteria for the diagnosis and classification criteria for type 2 diabetes mellitus;
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18 ≤ age ≤ 75 years old, male or female;
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Body mass index (BMI) within the range of 19-35 kg/m2 (inclusive), BMI = weight (kg) / height2 (m^2);
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7.0% ≤Hemoglobin A1c (HbA1c) ≤ 9.5%;
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Patients who voluntarily participate in the study and sign the informed consent form;
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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:
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Fasting plasma glucose (FPG) > 13.9 mmol/L;
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The investigator determines that the patients need to use insulin therapy;
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Patients with acute or serious complications of diabetes (including diabetic ketoacidosis, hyperosmotic nonketotic diabetic coma, lactic acidosis and hypoglycemia coma);
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History of severe hypoglycemia (hypoglycemia with severe cognitive impairment and requiring other measures to help recover);
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History of acute or chronic pancreatitis, or related diseases that are most common cause of acute pancreatitis (such as recurrent cholelithiasis, etc.);
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History of allergy to DPP-4 inhibitors or the investigator determines that the patients may be allergic to investigational drug;
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Patients with untreated hyperthyroidism and other diseases, which may affect blood glucose;
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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;
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Patients with inflammatory bowel disease, partial intestinal obstruction or chronic bowel disease related to obvious digestive and absorption disorders;
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Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 3 * upper limit of normal (ULN), or total bilirubin > 1.5 *ULN;
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Abnormal renal function: serum creatinine>1.5 * ULN; or eGFR< 45 mL/min/1.73m^2;
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White blood cells (WBC) < 3.0 *109/L and neutrophil count of peripheral blood < 1.5 * 109/L; hemoglobin < 100 g / L; triglyceride > 5.7 mmol/L;
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Patients who have the second or third degree atrioventricular block, long Q-T syndrome, or QTc>500 ms without cardiac pacemaker;
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Patients with any one of HBsAg, hepatitis C antibody, anti-HIV antibody and antibody of treponema pallidum positive;
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Female patients of childbearing age with pregnant test positive or lactating women;
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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;
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Patients who smoke more than 5 cigarettes per day within 3 months prior to screening;
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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;
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Participation in other clinical trials or administration of any other investigational drugs or devices within 3 months before screening;
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Patients with the following diseases:
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Serious dysrhythmias, obvious left ventricular dysfunction, New York Heart Association (NYHA) functional class III or IV;
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History of unstable angina pectoris, myocardial infarction, or other high-risk coronary artery diseases;
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Uncontrolled hypertension, systolic pressure ≥160 mmHg or diastolic pressure ≥100 mmHg;
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History of cancer , organ transplantation;
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History of epilepsy, psychosis, severe depression, etc.
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Not suitable for this study as determined by the investigator due to other reasons.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Anzhen Hospital, Capital Medical University | Beijing | Beijing | China | 100000 |
Sponsors and Collaborators
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Investigators
- Principal Investigator: Yang Lin, PhD, Beijing Anzhen Hospital of Capital Medical University , Beijing, China
- Principal Investigator: Shan NA Jing, PhD, Beijing Anzhen Hospital of Capital Medical University , Beijing, China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HA1118-014