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

Sponsor

Jiangsu HengRui Medicine Co., Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05273775

Collaborator

(none)

Enrollment

Arm

1.5

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	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	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single-center, single arm, open-label, fixed sequence, self-controlSingle-center, single arm, open-label, fixed sequence, self-control

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Anticipated Study Start Date :

Mar 15, 2022

Anticipated Primary Completion Date :

May 1, 2022

Anticipated Study Completion Date :

May 1, 2022

Arms and Interventions

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: HRS5091 Tablets HRS5091 Tablets once daily 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: Digoxin Tablets Digoxin Tablets single dose Drug: Rosuvastatin Calcium Tablets Rosuvastatin Calcium Tablets single dose

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: HRS5091 Tablets

HRS5091 Tablets once daily

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: Digoxin Tablets

Digoxin Tablets single dose

Drug: Rosuvastatin Calcium Tablets

Rosuvastatin Calcium Tablets single dose

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

The subject can communicate well with the researcher, understand and comply with the requirements of this study, and understand and sign the informed consent;
Healthy subjects aged 18~50 (including 18 and 50 years old);
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));
Give informed consent not to have a family plan for six months after the last dose, and agree to take effective contraception.

Exclusion Criteria:

Has the medicine or food allergy history, or is the allergic constitution person;
Inability to swallow, chronic diarrhea and intestinal obstruction, or the presence of a variety of other factors affecting drug use and absorption;
QTCF > 450 ms in 12-lead ECG examination or other abnormal conditions judged by the researchers to have clinical significance;
Hepatitis B surface Antigen (HBSAG), Hepatitis C virus antibody, human immunodeficiency virus (HIV) antibody, syphilis antibody test positive;
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;
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;
Having a history of drug abuse, drug dependence (consultation) or positive urine drug abuse screening before drug administration;
Anyone who has undergone any surgery within 6 months prior to screening;
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.