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

NCT05392127 | Completed Phase 1

• 1 other identifier: SHR0302-111
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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

Study Arms (1)

single arm

EXPERIMENTAL

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

Drug: SHR0302 Tablets; Drug: Midazolam Maleate Tablets; Drug: Warfarin Sodium Tablets; Drug: Omeprazole Enteric Capsules; Drug: Vitamin K1 Tablets; Drug: Repaglinide Tablets

Interventions

SHR0302 Tablets DRUG

SHR0302 Tablets once daily

single arm

Midazolam Maleate Tablets DRUG

Midazolam Maleate Tablets single dose

single arm

Warfarin Sodium Tablets DRUG

Warfarin Sodium Tablets single dose

single arm

Omeprazole Enteric Capsules DRUG

Omeprazole Enteric Capsules single dose

single arm

Vitamin K1 Tablets DRUG

Vitamin K1 Tablets once daily

single arm

Repaglinide Tablets DRUG

Repaglinide Tablets single dose

single arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \- 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430000, China

Location

Related Publications (1)

• Fu M, Luo L, Feng S, Lin H, Lu Z, Gu F, Fan Y, Wu B, Huang J, Shen K. Effect of SHR0302 on the pharmacokinetics of CYP3A4, CYP2C8, CYP2C9 and CYP2C19 probe substrates in healthy volunteers: A cocktail analysis. Br J Clin Pharmacol. 2023 Dec;89(12):3659-3668. doi: 10.1111/bcp.15856. Epub 2023 Aug 22.

  PMID: 37464978 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

ivarmacitinib; Midazolam; Warfarin; Vitamin K 1; repaglinide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Vitamin K; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-center, single arm, open-label, fixed sequence, self-control

Study Record Dates

• First Submitted: May 23, 2022
• First Posted: May 26, 2022
• Study Start: July 15, 2022
• Primary Completion: August 18, 2022
• Study Completion: August 18, 2022
• Last Updated: December 22, 2022

Record last verified: 2022-12

Locations

CN (1)