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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05392127
• Other study ID #: SHR0302-111
• Status: Completed
• Phase: Phase 1
• Start date: July 15, 2022
• Est. completion date: August 18, 2022

Study information

• Verified date: December 2022
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 18, 2022
• Est. primary completion date: August 18, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• SHR0302 Tablets
SHR0302 Tablets once daily
• Midazolam Maleate Tablets
Midazolam Maleate Tablets single dose
• Warfarin Sodium Tablets
Warfarin Sodium Tablets single dose
• Omeprazole Enteric Capsules
Omeprazole Enteric Capsules single dose
• Vitamin K1 Tablets
Vitamin K1 Tablets once daily
• Repaglinide Tablets
Repaglinide Tablets single dose

Locations

Country	Name	City	State
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax,PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302		Days 1-29
Primary	AUC0-t,PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302		Days 1-29
Primary	AUC0-inf,PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302		Days 1-29
Secondary	Tmax,PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302		Days 1-29
Secondary	t1/2,PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302		Days 1-29
Secondary	CL/F,PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302		Days 1-29
Secondary	Vz/F,PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302		Days 1-29
Secondary	Number of subjects with adverse events and severity of adverse events		Up to 35 days