A Pharmacokinetic Study to Evaluate the Drug Interaction Between SHR0302 and CYP Substrates in Healthy Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: SHR0302 Tablets
* Drug: Midazolam Maleate Tablets
* Drug: Warfarin Sodium Tablets
* Drug: Omeprazole Enteric Capsules
* Drug: Vitamin K1 Tablets
* Drug: Repaglinide Tablets


Participation Criteria
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Eligibility Criteria
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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; Subjects with medical history of systemic inflammatory disease, autoimmune disease, recurrent herpes zoster, disseminated herpes zoster, disseminated herpes simplex; Subjects with a history of tuberculosis (TB) within six months prior to the screening period; Subjects with a history of hypoglycemic episodes or fasting blood glucose less than 2.8 mmol/L during screening； Subjects who took inhibitors or inducers of CYP3A4, CYP2C8, CYP2C9, or CYP2C19 within 28 days before the study; Subjects with contraindications for midazolam, warfarin, omeprazole, and repaglinide.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Single-center, single arm, open-label, fixed sequence, self-control
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm<br>SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets | Drug: SHR0302 Tablets<br>* SHR0302 Tablets once daily<br>Drug: Midazolam Maleate Tablets<br>* Midazolam Maleate Tablets single dose<br>Drug: Warfarin Sodium Tablets<br>* Warfarin Sodium Tablets single dose<br>Drug: Omeprazole Enteric Capsules<br>* Omeprazole Enteric Capsules single dose<br>Drug: Vitamin K1 Tablets<br>* Vitamin K1 Tablets once daily<br>Drug: Repaglinide Tablets<br>* Repaglinide Tablets single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302 |  | Days 1-29 | 
| 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 | 
| Number of subjects with adverse events and severity of adverse events |  | Up to 35 days |