Study on the Pharmacokinetic Effect of Itraconazole on SHR0302 Tablets in Healthy Subjects

Study on the Pharmacokinetic Effects of Single-centered, Open, Single-arm, Fixed-sequence Itraconazole on SHR0302 Tablets in Healthy Subjects

To evaluate the effect of oral itraconazole on the pharmacokinetics of SHR0302 in healthy subjects.

To evaluate the safety and tolerability of oral SHR0302 and itraconazole monotherapy and combination use in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: itraconazole、 SHR0302 tablets

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410000
      • The Third Hospital of Changsha

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Voluntarily sign an informed consent form prior to the commencement of activities related to this trial, be able to understand the procedures and methods of this trial, and be willing to strictly comply with the clinical trial protocol to complete this trial;
2. Age 18 to 45 years (inclusive, subject to the signing of informed consent), healthy male;
3. Body mass ≥ 50 kg and body mass index (BMI): 19 to 26 kg/m2 (both ends included);
4. Be able to communicate well with the investigators and understand and comply with the requirements of this study.

Exclusion Criteria:

1. Those who have participated in clinical trials of any drug and medical device within three months before the first administration or who are still in the follow-up period of a clinical study or 5 half-life periods of the test drug before screening (whichever is longer), the participant in the clinical trial is defined as: those who have signed informed consent for clinical trials and have used the test drugs (including placebo) or experimental medical devices;
2. Those who have chronic or active gastrointestinal diseases such as esophageal diseases, gastritis, gastric ulcers, enteritis, active gastrointestinal bleeding or gastrointestinal surgery within three years and the researchers believe that there is still clinical significance;
3. Those who have a history of respiratory system, cardiovascular system, endocrine system, urinary system, nervous system, hematology, immunology (including personal or family history of hereditary immunodeficiency), metabolic abnormalities, etc., and the researcher believes that there is still clinical significance;
4. Patients with a history of ventricular dysfunction;
5. Have any history of systemic inflammatory diseases, autoimmune diseases, recurrent herpes zoster, disseminated herpes zoster, and disseminated herpes simplex;
6. Those who have a history of tuberculosis (TB) within half a year before the first administration;
7. Infections or other acute diseases that need to be treated with antimicrobials (viral, bacterial, fungal, parasitic infections) within 4 weeks before the first administration of the drug are judged by the researchers to be unsuitable for participating in the trial;
8. Allergic to the study drug (SHR0302 tablets and itraconazole capsules) or any ingredient in the study drug, or have a history of allergy to drugs, food or other substances;
9. Those who cannot tolerate intravenous puncture or have a history of blood sickness and needle sickness;
10. Those who have undergone surgery that the researchers judge will affect the absorption, distribution, metabolism and excretion of the drug within 6 months before the first administration; or have undergone surgery within 4 weeks before the first administration; or those who plan to perform surgical operations during the trial period;
11. Those who have used any drugs (including Chinese herbal medicines, health care products, etc.) within 14 days before the first administration, or those who plan to take drugs or health care products that are not experimental in this study during the trial period;
12. Any drug or food that has been used within 30 days prior to the first administration is an inhibitor or inducer of the cytochrome P4503A4 enzyme (CYP3A4), as detailed in Annex 2;
13. those who have received BCG vaccine within 12 months prior to the first dose, or who have been vaccinated or exposed to other live vaccines or live attenuated vaccines within 3 months prior to the first dose, or who plan to be vaccinated during the trial;
14. those who donate blood or lose a large amount of blood (> 400 mL) within 3 months before the first administration, those who receive blood transfusions or use blood products, or those who intend to donate blood or blood components during the trial period or within 3 months after the end of the test;
15. Drug abusers or those who have used soft drugs (such as marijuana) or hard drugs (such as cocaine, phencyclidine, etc.) within 1 year before the first administration of drugs;
16. Smokers or smokers with more than 5 cigarettes per day in the 3 months before the first administration, or who cannot stop using any tobacco-based products during the trial;
17. Alcoholics or regular drinkers in the 6 months prior to the first administration of the drug, i.e. those who drink more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of spirits or 150 mL of wine with an alcohol content of 45 mL); or are unwilling to stop drinking alcohol or any alcoholic products during the trial;
18. those who drink excessive amounts of tea, coffee and/or caffeinated beverages (more than 8 cups, 1 cup = 250 mL) per day, or those who do not agree to stop drinking tea, coffee and/or caffeinated beverages during the trial period;
19. those who have eaten any beverage or food containing grapefruit within 7 days before the first administration, or any beverage or food containing methylxanthine, such as coffee, tea, cola, chocolate, etc., within 48 hours before the first administration; or do not agree to stop eating the above diet during the trial period;
20. Those who have special requirements for diet and cannot comply with the unified diet;
21. During the test period, strenuous exercise cannot be stopped, or there are other factors that may affect the absorption, distribution, metabolism, excretion and other factors of the drug;
22. Volunteers who have a fertility plan, a sperm donation and egg donation plan during the trial period and 6 months after the end of the trial, or are unwilling to take one or more non-drug contraceptive measures (such as complete abstinence, condoms, contraceptive rings, partner sterilization, etc.);
23. Abnormal clinical significance of physical examination, electrocardiogram, vital signs, color ultrasound of the heart and abdomen, chest orthostatic film, and laboratory examination (subject to the judgment of the clinician);
24. ECG examination QTc>440 ms;
25. Glomerular filtration rate (eGFR）<90 mL/min/1.73m2(Adopt simplified renal disease dietary adjustments (MDRDformula calculation,eGFR=186×[serum creatinine value (mg/dL）]-1.154×[Age (years)]-0.203oreGFR=186×[serum creatinine value (μmol/L）×0.01131]-1.154×[Age (years)]-0.203）;
26. Positive uremic screen test;
27. Positive alcohol breath test;
28. Volunteers may not be able to complete this study for other reasons or have other reasons that the researchers judge that they are not suitable to participate in the trial.

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: Treatment group; itraconazole and SHR0302 tablets	Drug: itraconazole、 SHR0302 tablets; Itraconazole 7 times and SHR0302 tablets twice. On the 8th day of this, itraconazole and SHR0302 tablets were taken simultaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
SHR0302 and its main metabolite AUC0-t	day 1 to day 11
SHR0302 and its main metabolite AUC0-inf	day 1 to day 11
SHR0302 and its main metabolite Cmax	day 1 to day 11

Secondary Outcome Measures

Outcome Measure	Time Frame
SHR0302 and its main metabolite Tmax (SHR0302 only)	day 1 to day 11
SHR0302 and its main metabolite t1/2 (SHR0302 only)	day 1 to day 11
SHR0302 and its main metabolite CL/F (SHR0302 only)	day 1 to day 11
SHR0302 and its main metabolite Vz/F (SHR0302 only)	day 1 to day 11
Adverse events	Day 1 to Day 17

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2022
• Primary Completion (Actual): July 11, 2022
• Study Completion (Actual): July 11, 2022

Study Registration Dates

• First Submitted: May 31, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Estimate): 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: SHR0302-110

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