Clinical trial NCT05392127: A Pharmacokinetic Study to Evaluate the Drug Interaction Between SHR0302 and CYP Substrates in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-05-26
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-center, single arm, open-label, fixed sequence, self-control
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Cmax，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
timeFrame: Days 1-29
measure: AUC0-t，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
timeFrame: Days 1-29
measure: AUC0-inf，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
timeFrame: Days 1-29
Secondary outcomes:
measure: Tmax，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
timeFrame: Days 1-29
measure: t1/2，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
timeFrame: Days 1-29
measure: CL/F，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
timeFrame: Days 1-29
measure: Vz/F，PK parameters of midazolam, s-warfarin, omeprazole, Repaglinide before and after oral administration of SHR0302
timeFrame: Days 1-29
measure: Number of subjects with adverse events and severity of adverse events
timeFrame: Up to 35 days
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
Study officials:
References: