A Pharmacokinetic Study to Evaluate the Drug Interaction Between HRS5091 and Probe Drugs in Healthy Volunteers

A Single-center, Single-arm, Open-label, Fixed-sequence, Self-controlled Study of the Effects of HRS5091 on the Pharmacokinetics of Midazolam, S-warfarin, Omeprazole, Digoxin and Rosuvastatin in Healthy Volunteers

This is a drug-drug interaction study conducted in healthy volunteers to evaluate the effect of HRS5091 on CYP3A4, CYP2C9, CYP2C19, P-gp, BCRP and OATP1B1, using midazolam, s-warfarin, omeprazole, digoxin and rosuvastatin as probe drugs.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Midazolam Maleate Tablets; Drug: Warfarin Sodium Tablets; Drug: Omeprazole Enteric Capsules; Drug: Vitamin K1 Tablets; Drug: HRS5091 Tablets; Drug: Digoxin Tablets; Drug: Rosuvastatin Calcium Tablets

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510260
      • The Second Affiliated Hospital of Guangzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. The subject can communicate well with the researcher, understand and comply with the requirements of this study, and understand and sign the informed consent;
2. Healthy subjects aged 18~50 (including 18 and 50 years old);
3. Body weight ≥ 50 kg, body mass index (BMI) within the range of 19 ~ 26 kg /m2 (including 19 and 26 kg/m2) (BMI= weight (kg)/height2 (m2));
4. Give informed consent not to have a family plan for six months after the last dose, and agree to take effective contraception.

Exclusion Criteria:

1. Has the medicine or food allergy history, or is the allergic constitution person;
2. Inability to swallow, chronic diarrhea and intestinal obstruction, or the presence of a variety of other factors affecting drug use and absorption;
3. QTCF > 450 ms in 12-lead ECG examination or other abnormal conditions judged by the researchers to have clinical significance;
4. Hepatitis B surface Antigen (HBSAG), Hepatitis C virus antibody, human immunodeficiency virus (HIV) antibody, syphilis antibody test positive;
5. Those who smoked more than 5 cigarettes per day within 3 months before screening and could not stop using any tobacco products during the trial period;
6. Regular drinkers who had consumed more than 14 units of alcohol per week (1 unit = 285 ml of beer, 25 ml of spirits, or 100 ml of wine) during the six months prior to screening and could not stop using any alcoholic product during the trial; positive Breath test for alcohol;
7. Having a history of drug abuse, drug dependence (consultation) or positive urine drug abuse screening before drug administration;
8. Anyone who has undergone any surgery within 6 months prior to screening;
9. Clinical trial participants who have participated in any drug or medical device within 3 months prior to screening (subject to the intervention of the experimental drug or medical device);10.Blood donation (or blood loss) within 3 months before screening and the amount of blood donation (or blood loss)≥400 ml, or receiving blood transfusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: single arm; HRS5091 + probe drugs (Midazolam Maleate Tablets+Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Digoxin Tablets+ Rosuvastatin Calcium) + Vitamin K1 Tablets

Drug: Midazolam Maleate Tablets; Midazolam Maleate Tablets single dose; Drug: Warfarin Sodium Tablets; Warfarin Sodium Tablets single dose; Drug: Omeprazole Enteric Capsules; Omeprazole Enteric Capsules single dose; Drug: Vitamin K1 Tablets; Vitamin K1 Tablets once daily; Drug: HRS5091 Tablets; HRS5091 Tablets once daily; Drug: Digoxin Tablets; Digoxin Tablets single dose; Drug: Rosuvastatin Calcium Tablets; Rosuvastatin Calcium Tablets single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax，PK parameters of midazolam, s-warfarin, omeprazole, digoxin, rosuvastatin before and after oral administration of HRS5091	Days 1-27
AUC0-t，PK parameters of midazolam, s-warfarin, omeprazole, digoxin, rosuvastatin before and after oral administration of HRS5091	Days 1-27
AUC0-∞，PK parameters of midazolam, s-warfarin, omeprazole, digoxin, rosuvastatin before and after oral administration of HRS5091	Days 1-27

Secondary Outcome Measures

Outcome Measure	Time Frame
Tmax，PK parameters of midazolam, s-warfarin, omeprazole, digoxin, rosuvastatin before and after oral administration of HRS5091	Days 1-27
t1/2，PK parameters of midazolam, s-warfarin, omeprazole, digoxin, rosuvastatin before and after oral administration of HRS5091	Days 1-27
CL/F，PK parameters of midazolam, s-warfarin, omeprazole, digoxin, rosuvastatin before and after oral administration of HRS5091	Days 1-27
Vz/F，PK parameters of midazolam, s-warfarin, omeprazole, digoxin, rosuvastatin before and after oral administration of HRS5091	Days 1-27
Number of subjects with adverse events and severity of adverse events	Up to 56 days

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2022
• Primary Completion (Actual): June 23, 2022
• Study Completion (Actual): June 23, 2022

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: March 8, 2022
• First Posted (Actual): March 10, 2022

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Fibrin Modulating Agents; Antimetabolites; Gastrointestinal Agents; Protective Agents; Cardiotonic Agents; Micronutrients; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Vitamins; Anticoagulants; Antifibrinolytic Agents; Hemostatics; Coagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Digoxin; Midazolam; Vitamin K; Rosuvastatin Calcium; Warfarin; Omeprazole; Vitamin K 1
• Other Study ID Numbers: HRS5091-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No