Healthy Subjects
Conditions
Brief summary
This is a three-part, single-center, open-label phase I clinical study to characterize the DDIs potential of DBPR108 with Warfarin sodium, Digoxin, or Probenecid in healthy subjects. This study also aims to evaluate the safety and tolerability of DBPR108 in the presence of Warfarin sodium, Digoxin, or Probenecid.
Detailed description
DBPR108 is a potent dipeptidylpeptidase-4 inhibitor. This study will be run in three parts to characterize the DDIs potential of DBPR108 with the expected concomitant drugs (Warfarin sodium, Digoxin, Probenecid) in Healthy Subjects. Each part of this study consists of a screening period (Day -14 to Day -1), a baseline period (Day -1), a treatment period, and a follow-up visit period. Approximately 14 subjects will be enrolled in each part of this study.
Interventions
Drug: Warfarin sodium, tablet, oral
DRUGDigoxin tablet
Drug: Digoxin, tablet, oral
DRUGProbenecid tablets
Drug: Probenecid, tablet, oral
DRUGDBPR108 tablets
Drug: DBPR108, tablet, oral
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions; 2. 18 to 45 years (inclusive), male and female; 3. Male subjects weight ≥50.0 kg and female subjects weight ≥45.0 kg. Body mass index (BMI): 18-28 kg/m\^2 (inclusive) (BMI= weight (kg)/height\^2 (m\^2)； 4. Subjects (including their partners) are willing to use effective contraceptives from screening to the 6 months after the last dose administration; 5. Subjects judged to be in good health by the investigator, based on the physical examination, vital signs examination, 12-lead electrocardiogram (ECG) examination and laboratory examination etc;
Exclusion criteria
1. Subjects who have a history of allergic conditions (such as asthma, urticaria), or have a history of allergy to any of the study drugs or other similarly structured drugs; 2. Subjects with a history of severe diseases, such as cardiovascular, respiratory, liver, gastrointestinal, endocrine, hematological, psychiatric/neurological systems diseases within 1 year prior to screening; 3. Subjects with a history of hypoglycemia or abnormal blood glucose at screening: fasting blood glucose \<70 mg/dL (3.9 mmol/L) or \>110 mg/dL (6.1 mmol/L); 4. Subjects who have previously undergone surgery that may affect the absorption, distribution, metabolism, or excretion of the drug (e.g., subtotal gastrectomy), or who have a scheduled surgical plan during the study period; 5. Use of any prescription drug, over-the-counter drug, or herbal medicine within 2 weeks prior to screening; 6. Have been vaccinated within 4 weeks prior to screening or who have a scheduled vaccinated plan during the study period; 7. History of drug abuse, or positive urine drug screen at screening; 8. Smoking more than 5 cigarettes per day within 3 months prior to screening，or who cannot stop using any tobacco products during the study period； 9. Average daily intake of alcohol is more than 28 g alcohol (male) or 14 g (female) (14 g ≈ 497 mL beer, or 44 mL spirits with low alcohol content, or 145 mL wine) within the 3 months prior to screening, or taking any product containing alcohol within 48 h before dosing, or a positive ethanol breath test at screening; 10. Consumption of grapefruit juice, methylxanthine-rich food or beverage (such as coffee, tea, cola, chocolate, energy drinks) within 48 h before the administration, or those who have had strenuous exercise, or have other factors affecting drug absorption, distribution, metabolism, excretion, etc; 11. Participation in another clinical trial within 3 months before screening (whichever is administrated)； 12. Blood donation (or blood loss) ≥400 mL, or receiving whole blood transfusions or erythrocyte suspension transfusions within 3 months prior to the screening; 13. Any positive test result of hepatitis B surface antigen, hepatitis C virus antibody, anti-human immunodeficiency virus antibody or anti-Treponema pallidum specific antibody; 14. Pregnant/lactating woman, or has a positive pregnancy test at screening; 15. Not suitable for this study as judged by the investigator; 16. Supplementary
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part one: Peak plasma concentration (Cmax) of S-warfarin and R-warfarin | Day 1 to Day 8, and Day 19 to Day 26 |
| Part one: Area under the plasma concentration versus time curve (AUC) of S-warfarin and R-warfarin | Day 1 to Day 8, and Day 19 to Day 26 |
| Part one: Peak plasma concentration (Cmax) of DBPR108 | Day 17 to Day 20 |
| Part one: Area under the plasma concentration versus time curve (AUC) of DBPR108 | Day 17 to Day 20 |
| Part two: Peak plasma concentration (Cmax) of Digoxin | Day 1 to Day 6, and Day 10 to Day 15 |
| Part two: Area under the plasma concentration versus time curve (AUC) of Digoxin | Day 1 to Day 6, and Day 10 to Day 15 |
| Part two: Peak plasma concentration (Cmax) of DBPR108 | Day 8 to Day 11 |
| Part two: Area under the plasma concentration versus time curve (AUC) of DBPR108 | Day 8 to Day 11 |
| Part three: Peak plasma concentration (Cmax) of DBPR108 | Day 1 to Day 3, and Day 7 to Day 9 |
| Part three: Area under the plasma concentration versus time curve (AUC) of DBPR108 | Day 1 to Day 3, and Day 7 to Day 9 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part two: Time to achieve maximum plasma concentration (Tmax) of Digoxin | Day 1 to Day 6, and Day 10 to Day 15 | — |
| Part two: Half-life(t1/2) of Digoxin | Day 1 to Day 6, and Day 10 to Day 15 | — |
| Part two: Apparent volume of Distribution(Vz/F) of Digoxin | Day 1 to Day 6, and Day 10 to Day 15 | — |
| Part two: Apparent clearance(CL/F) of Digoxin | Day 1 to Day 6, and Day 10 to Day 15 | — |
| Part two: Time to achieve maximum plasma concentration (Tmax) of DBPR108 | Day 8 to Day 11 | — |
| Part two: Half-life(t1/2) of DBPR108 | Day 8 to Day 11 | — |
| Part two: Apparent volume of Distribution(Vz/F) of DBPR108 | Day 8 to Day 11 | — |
| Part two: Apparent clearance(CL/F) of DBPR108 | Day 8 to Day 11 | — |
| Part three: Time to achieve maximum plasma concentration (Tmax) of DBPR108 | Day 1 to Day 3, and Day 7 to Day 9 | — |
| Part three: Half-life(t1/2) of DBPR108 | Day 1 to Day 3, and Day 7 to Day 9 | — |
| Part three: Apparent volume of Distribution(Vz/F) of DBPR108 | Day 1 to Day 3, and Day 7 to Day 9 | — |
| Part three: Apparent clearance(CL/F) of DBPR108 | Day 1 to Day 3, and Day 7 to Day 9 | — |
| Part three:Cumulative amount of drug excreted in urine(Ae) of DBPR108 | Day 1 to Day 3, and Day 7 to Day 9 | — |
| Part three: Cumulative fraction of the dose excreted(fe) of DBPR108 | Day 1 to Day 3, and Day 7 to Day 9 | — |
| Part three: Renal Clearance(CLR) of DBPR108 | Day 1 to Day 3, and Day 7 to Day 9 | — |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Up to Day 33 from screening for part one, up to Day 22 from screening for part two, and up to Day 16 from screening for part three. | Number of participants with treatment-related adverse events will be assessed by CTCAE v5.0. The AEs will be summarized according to the system organ class (SOC) and preferred term (PT), including the number and percentage of participants who had AEs. |
| Part one: Time to achieve maximum plasma concentration (Tmax) of S-warfarin and R-warfarin | Day 1 to Day 8, and Day 19 to Day 26 | — |
| Clinically significant changes from baseline in physical examination will be recorded as AEs at each visit time point. | Up to Day 33 from screening for part one, up to Day 22 from screening for part two, and up to Day 16 from screening for part three. | Physical examination includes general conditions, skin, mucous membranes, head, neck, chest, abdomen, spine, limbs, nervous system, and lymphatic system. |
| Clinically significant changes from baseline in vital signs examination will be recorded as AEs at each visit time point. | Up to Day 33 from screening for part one, up to Day 22 from screening for part two, and up to Day 16 from screening for part three. | Vital signs monitoring includes body temperature in degrees Celsius. |
| Clinically significant changes from baseline in routine blood test will be recorded as AEs at each visit time point. | Up to Day 33 from screening for part one, up to Day 22 from screening for part two, and up to Day 16 from screening for part three. | Routine blood test includes red blood cell count in 10\^12/L. |
| Clinically significant changes from baseline in blood biochemistry test will be recorded as AEs at each visit time point. | Up to Day 33 from screening for part one, up to Day 22 from screening for part two, and up to Day 16 from screening for part three. | Blood biochemistry test includes total protein and albumin in g/L. |
| Clinically significant changes from baseline in routine urine test will be recorded as AEs at each visit time point. | Up to Day 33 from screening for part one, up to Day 22 from screening for part two, and up to Day 16 from screening for part three. | Routine urine test includes urobilinogen, glucose and protein in mg/dL. |
| Clinically significant changes from baseline in coagulation function test will be recorded as AEs at each visit time point. | Up to Day 33 from screening for part one, up to Day 22 from screening for part two, and up to Day 16 from screening for part three. | Coagulation action test includes fibrinogen in g/L. |
| Clinically significant changes from baseline in 12-lead electrocardiogram (ECG) examination will be recorded as AEs at each visit time point. | Up to Day 33 from screening for part one, up to Day 22 from screening for part two, and up to Day 16 from screening for part three. | ECG monitoring includes heart rate in bpm. |
| Part one: Half-life(t1/2) of S-warfarin and R-warfarin | Day 1 to Day 8, and Day 19 to Day 26 | — |
| Part one: Apparent volume of Distribution(Vz/F) of S-warfarin and R-warfarin | Day 1 to Day 8, and Day 19 to Day 26 | — |
| Part one: Apparent clearance(CL/F) of S-warfarin and R-warfarin | Day 1 to Day 8, and Day 19 to Day 26 | — |
| Part one: Time to achieve maximum plasma concentration (Tmax) of DBPR108 | Day 17 to Day 20 | — |
| Part one: Half-life(t1/2) of DBPR108 | Day 17 to Day 20 | — |
| Part one: Apparent volume of Distribution(Vz/F) of DBPR108 | Day 17 to Day 20 | — |
| Part one: Apparent clearance(CL/F) of DBPR108 | Day 17 to Day 20 | — |
| Part one: the pharmacodynamic parameters-Prothrombin time(PT) | Day 1 to Day 8, and Day 19 to Day 26 | — |
| Part one: the pharmacodynamic parameters-International normalized ratio(INR) | Day 1 to Day 8, and Day 19 to Day 26 | — |
Countries
China
Outcome results
None listed