A Study to Evaluate the Drug-drug Interactions (DDIs) of DBPR108 With Warfarin Sodium, Digoxin, Probenecid in Healthy Subjects

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.28 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Subjects

Interventions

Warfarin sodium tabletsDRUG

Drug: Warfarin sodium, tablet, oral

Digoxin tabletDRUG

Drug: Digoxin, tablet, oral

Probenecid tabletsDRUG

Drug: Probenecid, tablet, oral

DBPR108 tablets

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 exclusion criteria for the first part of the study: subjects with bleeding tendency, or PT and INR test results judged by the investigator to be not suitable for participating in the study; 17. Supplementary exclusion criteria for the third part of the study: the estimated glomerular filtration rate (eGFR) calculated by the modification of diet in renal diseases (MDRD) equation at screening with clinical significance as judged by the investigator, or subjects with nephrolithiasis or have a history of nephrolithiasis.

Locations (1)

First Affiliated Hospital of Soochow University

Suzhou, China

Outcomes

Primary Outcomes

Part one: Peak plasma concentration (Cmax) of S-warfarin and R-warfarin

Time frame: 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

Time frame: Day 1 to Day 8, and Day 19 to Day 26

Part one: Peak plasma concentration (Cmax) of DBPR108

Time frame: Day 17 to Day 20

Part one: Area under the plasma concentration versus time curve (AUC) of DBPR108

Time frame: Day 17 to Day 20

Part two: Peak plasma concentration (Cmax) of Digoxin

Time frame: Day 1 to Day 6, and Day 10 to Day 15

Part two: Area under the plasma concentration versus time curve (AUC) of Digoxin

Time frame: Day 1 to Day 6, and Day 10 to Day 15

Part two: Peak plasma concentration (Cmax) of DBPR108

Time frame: Day 8 to Day 11

Part two: Area under the plasma concentration versus time curve (AUC) of DBPR108

Time frame: Day 8 to Day 11

Part three: Peak plasma concentration (Cmax) of DBPR108

Time frame: Day 1 to Day 3, and Day 7 to Day 9

Part three: Area under the plasma concentration versus time curve (AUC) of DBPR108

Time frame: Day 1 to Day 3, and Day 7 to Day 9

Secondary Outcomes

Data from ClinicalTrials.gov

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Drug: DBPR108, tablet, oral

Part one: Time to achieve maximum plasma concentration (Tmax) of S-warfarin and R-warfarin

Time frame: Day 1 to Day 8, and Day 19 to Day 26

Part one: Half-life(t1/2) of S-warfarin and R-warfarin

Time frame: 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

Time frame: Day 1 to Day 8, and Day 19 to Day 26

Part one: Apparent clearance(CL/F) of S-warfarin and R-warfarin

Time frame: Day 1 to Day 8, and Day 19 to Day 26

Part one: Time to achieve maximum plasma concentration (Tmax) of DBPR108

Time frame: Day 17 to Day 20

Part one: Half-life(t1/2) of DBPR108

Time frame: Day 17 to Day 20

Part one: Apparent volume of Distribution(Vz/F) of DBPR108

Time frame: Day 17 to Day 20

Part one: Apparent clearance(CL/F) of DBPR108

Time frame: Day 17 to Day 20

Part one: the pharmacodynamic parameters-Prothrombin time(PT)

Time frame: Day 1 to Day 8, and Day 19 to Day 26

Part one: the pharmacodynamic parameters-International normalized ratio(INR)

Time frame: Day 1 to Day 8, and Day 19 to Day 26

Part two: Time to achieve maximum plasma concentration (Tmax) of Digoxin

Time frame: Day 1 to Day 6, and Day 10 to Day 15

Part two: Half-life(t1/2) of Digoxin

Time frame: Day 1 to Day 6, and Day 10 to Day 15

Part two: Apparent volume of Distribution(Vz/F) of Digoxin

Time frame: Day 1 to Day 6, and Day 10 to Day 15

Part two: Apparent clearance(CL/F) of Digoxin

Time frame: Day 1 to Day 6, and Day 10 to Day 15

Part two: Time to achieve maximum plasma concentration (Tmax) of DBPR108

Time frame: Day 8 to Day 11

Part two: Half-life(t1/2) of DBPR108

Time frame: Day 8 to Day 11

Part two: Apparent volume of Distribution(Vz/F) of DBPR108

Time frame: Day 8 to Day 11

Part two: Apparent clearance(CL/F) of DBPR108

Time frame: Day 8 to Day 11

Part three: Time to achieve maximum plasma concentration (Tmax) of DBPR108

Time frame: Day 1 to Day 3, and Day 7 to Day 9

Part three: Half-life(t1/2) of DBPR108

Time frame: Day 1 to Day 3, and Day 7 to Day 9

Part three: Apparent volume of Distribution(Vz/F) of DBPR108

Time frame: Day 1 to Day 3, and Day 7 to Day 9

Part three: Apparent clearance(CL/F) of DBPR108

Time frame: Day 1 to Day 3, and Day 7 to Day 9

Part three:Cumulative amount of drug excreted in urine(Ae) of DBPR108

Time frame: Day 1 to Day 3, and Day 7 to Day 9

Part three: Cumulative fraction of the dose excreted(fe) of DBPR108

Time frame: Day 1 to Day 3, and Day 7 to Day 9

Part three: Renal Clearance(CLR) of DBPR108

Time frame: 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

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.