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

Sponsor

Jiangsu HengRui Medicine Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05392127

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Days)

146.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: SHR0302 Tablets Drug: Midazolam Maleate Tablets Drug: Warfarin Sodium Tablets Drug: Omeprazole Enteric Capsules Drug: Vitamin K1 Tablets Drug: Repaglinide Tablets	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single-center, single arm, open-label, fixed sequence, self-controlSingle-center, single arm, open-label, fixed sequence, self-control

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Anticipated Study Start Date :

Jul 15, 2022

Anticipated Primary Completion Date :

Jul 20, 2022

Anticipated Study Completion Date :

Jul 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: single arm SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets	Drug: SHR0302 Tablets SHR0302 Tablets once daily Drug: Midazolam Maleate Tablets Midazolam Maleate Tablets single dose Drug: Warfarin Sodium Tablets Warfarin Sodium Tablets single dose Drug: Omeprazole Enteric Capsules Omeprazole Enteric Capsules single dose Drug: Vitamin K1 Tablets Vitamin K1 Tablets once daily Drug: Repaglinide Tablets Repaglinide Tablets single dose

Arm

Intervention/Treatment

Experimental: single arm

SHR0302 Tablets + probe drugs (Midazolam Maleate Tablets + Warfarin Sodium Tablets+ Omeprazole Enteric Capsules+ Repaglinide Tablets) + Vitamin K1 Tablets

Drug: SHR0302 Tablets

SHR0302 Tablets once daily

Drug: Midazolam Maleate Tablets

Midazolam Maleate Tablets single dose

Drug: Warfarin Sodium Tablets

Warfarin Sodium Tablets single dose

Drug: Omeprazole Enteric Capsules

Omeprazole Enteric Capsules single dose

Drug: Vitamin K1 Tablets

Vitamin K1 Tablets once daily

Drug: Repaglinide Tablets

Repaglinide Tablets single dose

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts 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:

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.