Rheumatoid Arthritis
Conditions
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.
Interventions
DRUGSHR0302 Tablets
SHR0302 Tablets once daily
Midazolam Maleate Tablets single dose
Warfarin Sodium Tablets single dose
Omeprazole Enteric Capsules single dose
Vitamin K1 Tablets once daily
DRUGRepaglinide Tablets
Repaglinide Tablets single dose
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Single-center, single arm, open-label, fixed sequence, self-control
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
1. Subjects with known history or suspected of being allergic to the study drugs； 2. Participation in clinical trials of other investigational drugs or medical devices within 3 months prior to screening 3. Subjects with eGFR less than 90 mL/min/1.73m2； 4. 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; 5. Subjects whoes12-Lead ECG QTcF was more than 450 ms or there were other abnormalities determined by the investigator； 6. Subjects with clinically significant abnormalities in coagulation function； 7. Subjects with infectious disease； 8. Subjects with positive of urine drug screen； 9. Subjects with acute illness occurred within 4 weeks prior to the screening period; 10. Subjects who required antimicrobial therapy within 4 weeks prior to the screening period; 11. Subjects with medical history of systemic inflammatory disease, autoimmune disease, recurrent herpes zoster, disseminated herpes zoster, disseminated herpes simplex; 12. Subjects with a history of tuberculosis (TB) within six months prior to the screening period; 13. Subjects with a history of hypoglycemic episodes or fasting blood glucose less than 2.8 mmol/L during screening； 14. Subjects who took inhibitors or inducers of CYP3A4, CYP2C8, CYP2C9, or CYP2C19 within 28 days before the study; 15. Subjects with contraindications for midazolam, warfarin, omeprazole, and repaglinide.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302 | Days 1-29 |
| AUC0-t，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302 | Days 1-29 |
| AUC0-inf，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302 | Days 1-29 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
China
Outcome results
None listed