A Single-center, Open-label, Single-arm, Fixed-sequence Study to Evaluate the Pharmacokinetic Effects of SHR0302 Tablets on Substrates of CYP3A4, CYP2C8, CYP2C9, CYP2C19 in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- SHR0302 Tablets
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- AUC0-t，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a drug-drug interaction study conducted in healthy volunteers to evaluate the pharmacokinetic effect of SHR0302 on CYP3A4, CYP2C9, CYP2C9, CYP2C19, using midazolam, s-warfarin, omeprazole, and repaglinide as probe drugs.
Investigators
Eligibility Criteria
Inclusion Criteria
- •1.18 ≤ age ≤45, healthy male; 2.Subjects with body weight ≥ 50 kg, and 19≤BMI ≤26 kg/m2 ； 3.Subjects must agree to take effective contraceptive methods from signing informed consent to 6 months after the last administration.
Exclusion Criteria
- •Subjects with known history or suspected of being allergic to the study drugs；
- •Participation in clinical trials of other investigational drugs or medical devices within 3 months prior to screening
- •Subjects with eGFR less than 90 mL/min/1.73m2；
- •Subjects with systolic blood pressure less than 90 mmHg or more than 140 mmHg, and/or diastolic blood pressure less than 60 mmHg or more than 90 mmHg;
- •Subjects whoes12-Lead ECG QTcF was more than 450 ms or there were other abnormalities determined by the investigator；
- •Subjects with clinically significant abnormalities in coagulation function；
- •Subjects with infectious disease；
- •Subjects with positive of urine drug screen；
- •Subjects with acute illness occurred within 4 weeks prior to the screening period;
- •Subjects who required antimicrobial therapy within 4 weeks prior to the screening period;
Arms & Interventions
single arm
SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
Intervention: SHR0302 Tablets
single arm
SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
Intervention: Midazolam Maleate Tablets
single arm
SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
Intervention: Warfarin Sodium Tablets
single arm
SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
Intervention: Omeprazole Enteric Capsules
single arm
SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
Intervention: Vitamin K1 Tablets
single arm
SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
Intervention: Repaglinide Tablets
Outcomes
Primary Outcomes
AUC0-t，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
Time Frame: Days 1-29
AUC0-inf，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
Time Frame: Days 1-29
Cmax，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
Time Frame: Days 1-29
Secondary Outcomes
- t1/2，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302(Days 1-29)
- CL/F，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302(Days 1-29)
- Vz/F，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302(Days 1-29)
- Tmax，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302(Days 1-29)
- Number of subjects with adverse events and severity of adverse events(Up to 35 days)