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

NCT05045313 | Completed Phase 1

• 1 other identifier: HA1118-CSP-012
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (45)

• 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

• 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

Study Arms (3)

The DDI of DBPR108 and Warfarin Sodium Tablets

EXPERIMENTAL

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.

Drug: Warfarin sodium tablets; Drug: DBPR108 tablets

The DDI of DBPR108 and Digoxin Tablets

EXPERIMENTAL

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.

Drug: Digoxin tablet; Drug: DBPR108 tablets

The DDI of DBPR108 and Probenecid Tablets

EXPERIMENTAL

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.

Drug: Probenecid tablets; Drug: DBPR108 tablets

Interventions

Warfarin sodium tablets DRUG

Drug: Warfarin sodium, tablet, oral

The DDI of DBPR108 and Warfarin Sodium Tablets

Digoxin tablet DRUG

Drug: Digoxin, tablet, oral

The DDI of DBPR108 and Digoxin Tablets

Probenecid tablets DRUG

Drug: Probenecid, tablet, oral

The DDI of DBPR108 and Probenecid Tablets

DBPR108 tablets DRUG

Drug: DBPR108, tablet, oral

Also known as: DBPR108

The DDI of DBPR108 and Digoxin Tablets; The DDI of DBPR108 and Probenecid Tablets; The DDI of DBPR108 and Warfarin Sodium Tablets

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;
• to 45 years (inclusive), male and female;
• 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)；
• Subjects (including their partners) are willing to use effective contraceptives from screening to the 6 months after the last dose administration;
• 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;

You may not qualify if:

• 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;
• 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;
• 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);
• 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;
• Use of any prescription drug, over-the-counter drug, or herbal medicine within 2 weeks prior to screening;
• Have been vaccinated within 4 weeks prior to screening or who have a scheduled vaccinated plan during the study period;
• History of drug abuse, or positive urine drug screen at screening;
• 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；
• 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;
• 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;
• Participation in another clinical trial within 3 months before screening (whichever is administrated)；
• Blood donation (or blood loss) ≥400 mL, or receiving whole blood transfusions or erythrocyte suspension transfusions within 3 months prior to the screening;
• Any positive test result of hepatitis B surface antigen, hepatitis C virus antibody, anti-human immunodeficiency virus antibody or anti-Treponema pallidum specific antibody;
• Pregnant/lactating woman, or has a positive pregnancy test at screening;
• Not suitable for this study as judged by the investigator;

Sponsors & Collaborators

• CSPC ZhongQi Pharmaceutical Technology Co., Ltd.: lead

Study Sites (1)

First Affiliated Hospital of Soochow University

Suzhou, China

Location

MeSH Terms

Interventions

Warfarin; Digoxin; Probenecid; DBPR108

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: September 16, 2021
• Study Start: October 20, 2021
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: March 10, 2022

Record last verified: 2021-08

Locations

CN (1)