Drug Interactions
Conditions
Keywords
Drugs, interacting drugs
Brief summary
This is a Phase 1, single-center, open-label study designed to evaluate the effect of itraconazole on the pharmacokinetics of HRS-4642 in healthy adult participants. Approximately 18 healthy participants will be enrolled. Each participant will receive HRS-4642 alone by intravenous infusion, followed by HRS-4642 in combination with oral itraconazole. Blood samples will be collected to measure HRS-4642 concentrations and assess whether itraconazole affects how HRS-4642 is processed by the body. The safety of HRS-4642 administered alone and in combination with itraconazole will also be evaluated throughout the study.
Detailed description
This is a Phase 1, single-center, single-arm, open-label, fixed-sequence study to evaluate the effect of itraconazole on the pharmacokinetics of HRS-4642 following intravenous infusion in healthy adult participants. Approximately 18 healthy participants aged 18 to 45 years will be enrolled. On Day 1, participants will receive a single 200 mg dose of HRS-4642 by intravenous infusion. Blood samples for pharmacokinetic assessment will be collected through Day 17. From Day 18 to Day 36, participants will receive itraconazole 200 mg orally once daily. On Day 21, participants will receive a second 200 mg intravenous infusion of HRS-4642 in combination with itraconazole. Blood samples for pharmacokinetic assessment will be collected through Day 37. Pharmacokinetic parameters of HRS-4642 following administration alone and in combination with itraconazole will be evaluated to assess the potential drug-drug interaction. Safety assessments will include adverse events, physical examinations, vital signs, laboratory tests, and 12-lead electrocardiograms. Participants will undergo safety follow-up after completion of study treatment.
Interventions
DRUGHRS-4642
HRS-4642 injection will be administered at a dose of 200 mg by intravenous infusion on Day 1 and Day 21. The recommended infusion duration is 100 ± 10 minutes, including flushing.
Itraconazole capsules will be administered orally at a dose of 200 mg once daily after breakfast from Day 18 through Day 36, for a total of 19 days. On Day 21, HRS-4642 will be administered by intravenous infusion within 10 minutes after oral administration of itraconazole.
Sponsors
The Third Xiangya Hospital of Central South University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy participants aged 18 to 45 years (inclusive) at the time of signing the informed consent form. 2. Male participants with a body weight of at least 50.0 kg and female participants with a body weight of at least 45.0 kg, and a body mass index between 19 and 26 kg/m² (inclusive). 3. Women of childbearing potential who have not undergone surgical sterilization must use highly effective contraception from signing the informed consent form until 1 month after the last dose of HRS-4642. Male participants with female partners of childbearing potential must also use highly effective contraception during the same period. Women of childbearing potential must have a negative serum human chorionic gonadotropin test within 14 days before the first dose and must not be breastfeeding. 4. Participants who are able to communicate effectively with the investigator, understand and comply with all study requirements, and voluntarily sign the informed consent form. \*\*
Exclusion criteria
\*\* 1. History or presence of any clinically significant serious disease involving the cardiovascular, endocrine, neurological, gastrointestinal, respiratory, genitourinary, hematological, immunological, psychiatric, or metabolic systems, or any other condition that may interfere with the study results. 2. Poorly controlled or severe cardiovascular or cerebrovascular disease, or arterial or venous thrombotic events within 6 months before study entry, including cerebral hemorrhage, cerebral infarction, severe or unstable angina, symptomatic congestive heart failure (New York Heart Association Class II-IV), myocardial infarction, arrhythmias requiring medical intervention, or deep vein thrombosis. 3. Carotid artery stenosis of at least 50% on ultrasonography (preferably assessed using the European Carotid Surgery Trial method), or the presence of more than two high-risk plaque features. 4. Low-density lipoprotein cholesterol, total cholesterol, or triglyceride levels above the upper limit of the study site's reference range at screening, or moderate or higher risk of atherosclerotic cardiovascular disease as assessed by the investigator according to the Chinese Guidelines for Lipid Management (2023). 5. History of surgery within 6 months before screening or planned surgery during the study. 6. History of any surgery affecting gastrointestinal absorption, including gastrectomy, intestinal resection, or bariatric surgery, or a need for gastric acid-neutralizing medications during the study. 7. Blood donation or significant blood loss of at least 400 mL, blood transfusion, or use of blood products within 3 months before screening. 8. History of severe drug allergy or hypersensitivity reactions, or known hypersensitivity to HRS-4642 injection, itraconazole, or any of their excipients. 9. Regular use of sedatives, hypnotics, or other addictive medications; history of drug abuse within 1 year before screening; or a positive urine drug abuse screening test. 10. Use of potentially hepatotoxic medications, such as dapsone, erythromycin, fluconazole, ketoconazole, or rifampicin, for more than 7 consecutive days within 6 months before screening. 11. Participation in any clinical trial involving administration of an investigational drug within 3 months before the first dose. 12. Use of medications affecting hepatic enzyme activity or P-glycoprotein activity within 28 days before administration of the study drug. 13. Use of any prescription medications or traditional herbal supplements within 1 month before the first dose, or any over-the-counter medications or dietary supplements, including vitamins and calcium supplements, within 2 weeks before the first dose. 14. Smoking more than 5 cigarettes per day within 3 months before screening and inability to abstain from tobacco products during the study. 15. Regular alcohol consumption exceeding 14 units per week within 6 months before screening and inability to abstain from alcohol during the study, or a positive alcohol breath test. One unit of alcohol is equivalent to 285 mL of beer, 25 mL of spirits, or 100 mL of wine. 16. Clinically significant abnormalities in vital signs, physical examination, 12-lead electrocardiogram, abdominal ultrasonography, chest radiography, hematology, blood biochemistry, urinalysis, or coagulation tests during screening. 17. Positive screening results for hepatitis B surface antigen, hepatitis C antibody, syphilis antibody, or human immunodeficiency virus antibody. 18. Consumption of and unwillingness to abstain from methylxanthine-containing foods or beverages, such as coffee, tea, cola, or chocolate, from 48 hours before the first dose until study withdrawal; consumption of and unwillingness to abstain from grapefruit-containing foods or beverages from 14 days before the first dose until study withdrawal; or special dietary requirements that prevent compliance with standardized meals. 19. History of fainting in response to needles or blood, difficulty with blood collection, or inability to tolerate venipuncture. 20. Pregnant or breastfeeding women. 21. Any other condition that, in the investigator's opinion, makes the participant unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Total HRS-4642 Following Administration Alone | From within 30 minutes before HRS-4642 infusion on Day 1 through 384 hours after completion of the infusion (Day 17). | The maximum observed plasma concentration of total HRS-4642 following a single intravenous infusion of HRS-4642 alone, determined from the plasma concentration-time profile. |
Outcome results
None listed