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

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: SHR0302 Tablets; Drug: Midazolam Maleate Tablets; Drug: Warfarin Sodium Tablets; Drug: Omeprazole Enteric Capsules; Drug: Vitamin K1 Tablets; Drug: Repaglinide Tablets

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Zhongnan Hospital of Wuhan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2022
• Primary Completion (Actual): August 18, 2022
• Study Completion (Actual): August 18, 2022

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Actual): December 22, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Fibrin Modulating Agents; Gastrointestinal Agents; Micronutrients; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Vitamins; Anticoagulants; Antifibrinolytic Agents; Hemostatics; Coagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Midazolam; Vitamin K; Warfarin; Omeprazole; Vitamin K 1; Repaglinide
• Other Study ID Numbers: SHR0302-111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No