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

NCT05273775 | Completed Phase 1

• 1 other identifier: HRS5091-102
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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

Study Arms (1)

single arm

EXPERIMENTAL

HRS5091 + probe drugs (Midazolam Maleate Tablets+Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Digoxin Tablets+ Rosuvastatin Calcium) + Vitamin K1 Tablets

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

Interventions

HRS5091 Tablets DRUG

HRS5091 Tablets once daily

single arm

Midazolam Maleate Tablets DRUG

Midazolam Maleate Tablets single dose

single arm

Warfarin Sodium Tablets DRUG

Warfarin Sodium Tablets single dose

single arm

Omeprazole Enteric Capsules DRUG

Omeprazole Enteric Capsules single dose

single arm

Vitamin K1 Tablets DRUG

Vitamin K1 Tablets once daily

single arm

Digoxin Tablets DRUG

Digoxin Tablets single dose

single arm

Rosuvastatin Calcium Tablets DRUG

Rosuvastatin Calcium Tablets single dose

single arm

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510260, China

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Midazolam; Warfarin; Vitamin K 1; Digoxin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Vitamin K; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-center, single arm, open-label, fixed sequence, self-control

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: March 10, 2022
• Study Start: April 29, 2022
• Primary Completion: June 23, 2022
• Study Completion: June 23, 2022
• Last Updated: December 23, 2022

Record last verified: 2022-12

Locations

CN (1)