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

CSPC Pharmaceutical Group

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: Digoxin tablet; Drug: DBPR108 tablets; Drug: Probenecid tablets; Drug: Warfarin sodium tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT05045313

HA1118-CSP-012

Details and patient eligibility

About

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.

Full 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.

Enrollment: 28 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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28 participants in 3 patient groups

The DDI of DBPR108 and Warfarin Sodium Tablets

Experimental group

Description:

Subjects will receive a single dose of Warfarin sodium 5 mg on Day 1, then take DBPR108 100 mg once-daily on Day 15 through Day 26 and a single dose of Warfarin sodium 5 mg on Day 19.

Treatment:

Drug: Warfarin sodium tablets

Drug: DBPR108 tablets

The DDI of DBPR108 and Digoxin Tablets

Experimental group

Description:

Subjects will receive a single dose of Digoxin 0.25 mg on Day 1, then take DBPR108 100 mg once-daily on Day 6 through Day 15 and a single dose of Digoxin 0.25 mg on Day 10.

Treatment:

Drug: Digoxin tablet

Drug: DBPR108 tablets

The DDI of DBPR108 and Probenecid Tablets

Experimental group

Description:

Subjects will receive a single dose of DBPR108 100 mg on Day 1, then take Probenecid 500 mg twice-daily on Day 5 through Day 9 and a single dose of DBPR108 100 mg on Day 7.

Treatment:

Drug: Probenecid tablets

Drug: DBPR108 tablets