A Study to Evaluate the Effect of Itraconazole on Pharmacokinetics (PK) of SHR8554 in Healthy Adult Subjects

Study Overview
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Brief Summary
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This drug-drug interaction (DDI) study has been designed to characterize the pharmacokinetic profile of SHR8554 when co administered with a strong cytochrome P450 3A4 (CYP3A4) inhibitor itraconazole

Official Title
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A Phase 1, Open-label, Fixed-sequence Study to Estimate the Effects of Multiple-dose Administration of Itraconazole on the Pharmacokinetics of SHR8554 in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: SHR8554；Itraconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects, aged 18 to 45 years (inclusive). Female subjects body weight≥45 kg, male subjects body weight≥50 kg, body mass index (BMI) of 19.0 to 26.0 kg/m2 (inclusive). Understand the study procedures in the informed consent form and be willing and able to comply with the protocol. Exclusion Criteria: Subjects with a history of drug allergy, or a history of specific allergies, or known allergy to SHR8554 or itraconazole or similar. Any condition or disease detected during the medical interview/physical examination that would render the participant unsuitable for the study as determined by the investigator. Subjects with positive tests for infectious diseases. Subjects who have undergone major surgery within 3 months prior to screening or have undergone surgery that could significantly affect the in vivo course or safety evaluation of the study drug. History of using any medication within 2 weeks prior to the first dosing. Subjects who have received vaccination within 1 month prior to screening or plan to receive vaccination during the trial. Excessive daily consumption of tea, coffee, grapefruit/grapefruit juice and other special diets in the 1 month prior to screening. Subjects with a history of substance abuse, drug use or a positive screening test for substance abuse. Female who are pregnant or breastfeeding, or have a positive pregnancy test. Subjects who may not be able to complete the study for other reasons or who the investigator believes should not be included.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR8554 and itraconazole<br>SHR8554 will be provided in a solution. Participants will receive 1 mg SHR8554 by intravenous pump on Day 1 and Day 9. Itraconazole capsules 200 mg orally after meals twice daily for 7 days from Day 4 to Day 10. | Drug: SHR8554；Itraconazole<br>* Drug: SHR8554 Administered as specified in the treatment arm Drug: Itraconazole Administered as specified in the treatment arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax：observed maximum plasma concentration |  | Day 1 and Day 9 (pre-dose up to 48 hours post-dose) | 
| AUC0-t ：area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration |  | Day 1 and Day 9 (pre-dose up to 48 hours post-dose) | 
| AUC0-∞：area under the plasma concentration-time curve from time 0 to infinity |  | Day 1 and Day 9 (pre-dose up to 48 hours post-dose) | 
| Tmax：observed time to reach Cmax |  | Day 1 and Day 9 (pre-dose up to 48 hours post-dose) | 
| Vz ：apparent volume of distribution |  | Day 1 and Day 9 (pre-dose up to 48 hours post-dose) | 
| MRT0-∞：mean residence time from time 0 to infinity |  | Day 1 and Day 9 (pre-dose up to 48 hours post-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) |  | Baseline up to Day 18 | 
| Incidence of participants with clinical laboratory abnormalities |  | Baseline up to Day 18 | 
| Incidence of participants with vital signs abnormalities |  | Baseline up to Day 18 | 
| Incidence of participants with physical exam abnormalities |  | Baseline up to Day 18 |