Drug-durg Interaction of Leritrelvir(RAY1216) With Midazolam, Omeprazole, Rosuvastatin, Verapamil, and Rifampin

Study Overview
=================
Brief Summary
-----------------
The drug-drug interaction study had been designed to investigate the effect of Leritrelvir on the pharmacokinetics of Midazolam, Omeprazole, Rosuvastatin and the effect of Verapamil and Rifampin on the pharmacokinetics of Leritrelvir

Official Title
-----------------
A Open-Label, Two-sequence Phase I Drug-drug Interaction Clinical Study to Investigate the Pharmacokinetics of Leritrelvir With Midazolam, Omeprazole, Rosuvastatin, Verapamil, and Rifampin in Healthy Participants

Conditions
-----------------
Drug Drug Interaction

Intervention / Treatment
-----------------
* Drug: Midazolam
* Drug: Omeprazole
* Drug: Rosuvastatin
* Drug: Verapamil
* Drug: Rifampin
* Drug: Leritrelvir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body mass index (BMI) ≥19 to ≤26kg/m2 and total body weight >50 kg(male) or >45kg(female) at screening (calculated as a function of measured height and weight according to the formula, BMI = kg/m2 where m2 is height in meters squared); Ability to understand and willingness to sign a written informed consent form; Normal physical examination,vital signs,12-lead ECG, and clinical laboratory values, or any abnormality that is non-clinically significant. Exclusion Criteria: Participants with a history of hypersensitivity to study drug(Leritrelvir,Midazolam,Omeprazole,Rosuvastatin, Verapamil, and Rifampin) or any component of study medication; Participants had taken prescription, over-the-counter, herbal, or vitamin products within 14 days prior to 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; Participants who donated blood/bleeding profusely (>400 mL) 3 months prior to randomization; Those with clinically significant Electrocardiogram(ECG) abnormalities, or QTcF>450ms; Participants who test positive at screening for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody or Syphilis spirochete-specific antibodies (TPPA); Participants who test positive at screening and/or admission (Day -1) for alcohol abuse. Females who are pregnant, lactating, or likely to become pregnant during the study. History of dysphagia or any gastrointestinal disorder that affect absorption

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental 1<br>All participants will receive the following oral doses of study drugs following an overnight fast in the fixed-sequence below: Period 1: 1 × 15-mg Midazolam tablet ,1 ×20-mg omeprazole tablet ,1×10-mg rosuvastatin tablet Period 2: 6 × 400-mg Leritrelvir tablet+1 × 15-mg Midazolam tablet, 1 ×20-mg omeprazole tablet ,1×10-mg rosuvastatin tablet | Drug: Midazolam<br>* oral<br>Drug: Omeprazole<br>* oral<br>Drug: Rosuvastatin<br>* oral<br>Drug: Leritrelvir<br>* oral<br>|
| Experimental: Experimental 2<br>All participants will receive the following oral doses of study drugs following an overnight fast in the fixed-sequence below: Period 1: 1 × 400-mg Leritrelvir tablet Period 2: 5 × 240-mg verapamil tablet+1 × 400-mg Leritrelvir tablet Period 3: 8 × 600-mg rifampin capsule +1 × 400-mg Leritrelvir tablet | Drug: Verapamil<br>* oral<br>Drug: Rifampin<br>* oral<br>Drug: Leritrelvir<br>* oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic - Cmax | Maximum observed plasma concentration | 0-72 hours | 
| Pharmacokinetic -Area under the curve（AUC） | Area under the curve | 0-72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | The safety and tolerability of Leritrelvir alone and in combination with Midazolam, Omeprazole, Rosuvastatin, Verapamil, and Rifampin will be examined. | Day1-Day31 |