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

Phase 1

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Drug: HRS5091 Tablets; Drug: Midazolam Maleate Tablets; Drug: Warfarin Sodium Tablets; Drug: Omeprazole Enteric Capsules; Drug: Vitamin K1 Tablets; Drug: Digoxin Tablets; Drug: Rosuvastatin Calcium Tablets

• Registration Number: NCT05273775
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-03-01
• Study First Submitted QC: 2022-03-08
• Study First Posted: 2022-03-10
• Study Start: 2022-04-29
• Primary Completion: 2022-06-23
• Study Completion: 2022-06-23
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-22
• Last Update Posted: 2022-12-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 22

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
single arm	Omeprazole Enteric Capsules	HRS5091 + probe drugs (Midazolam Maleate Tablets+Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Digoxin Tablets+ Rosuvastatin Calcium) + Vitamin K1 Tablets
single arm	Warfarin Sodium Tablets	HRS5091 + probe drugs (Midazolam Maleate Tablets+Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Digoxin Tablets+ Rosuvastatin Calcium) + Vitamin K1 Tablets
single arm	Rosuvastatin Calcium Tablets	HRS5091 + probe drugs (Midazolam Maleate Tablets+Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Digoxin Tablets+ Rosuvastatin Calcium) + Vitamin K1 Tablets
single arm	HRS5091 Tablets	HRS5091 + probe drugs (Midazolam Maleate Tablets+Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Digoxin Tablets+ Rosuvastatin Calcium) + Vitamin K1 Tablets
single arm	Midazolam Maleate Tablets	HRS5091 + probe drugs (Midazolam Maleate Tablets+Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Digoxin Tablets+ Rosuvastatin Calcium) + Vitamin K1 Tablets
single arm	Vitamin K1 Tablets	HRS5091 + probe drugs (Midazolam Maleate Tablets+Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Digoxin Tablets+ Rosuvastatin Calcium) + Vitamin K1 Tablets
single arm	Digoxin Tablets	HRS5091 + probe drugs (Midazolam Maleate Tablets+Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Digoxin Tablets+ Rosuvastatin Calcium) + Vitamin K1 Tablets

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

The Second Affiliated Hospital of Guangzhou Medical University; 🇨🇳 Guangzhou, Guangdong, China