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

Phase 1

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: SHR0302 Tablets; Drug: Midazolam Maleate Tablets; Drug: Warfarin Sodium Tablets; Drug: Omeprazole Enteric Capsules; Drug: Vitamin K1 Tablets; Drug: Repaglinide Tablets

• Registration Number: NCT05392127
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-23
• Study First Submitted QC: 2022-05-23
• Study First Posted: 2022-05-26
• Study Start: 2022-07-15
• Primary Completion: 2022-08-18
• Study Completion: 2022-08-18
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-21
• Last Update Posted: 2022-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
single arm	SHR0302 Tablets	SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
single arm	Midazolam Maleate Tablets	SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
single arm	Warfarin Sodium Tablets	SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
single arm	Omeprazole Enteric Capsules	SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
single arm	Vitamin K1 Tablets	SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets
single arm	Repaglinide Tablets	SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets

Primary Outcome Measures

Name	Time	Method
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
Cmax，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302	Days 1-29

Secondary Outcome Measures

Name	Time	Method
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
Tmax，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302	Days 1-29

Trial Locations

Locations (1)

Zhongnan Hospital of Wuhan University; 🇨🇳 Wuhan, Hubei, China