Safety, Tolerability and Pharmacokinetics of HSK21542 in Healthy Volunteers

Study Overview
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Brief Summary
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This is a first-in-human, Phase I, single-dose escalation clinical trial conducted in Chinese healthy volunteers. The safety, tolerability, and PK of HSK21542 injection in healthy volunteers will be evaluated using a randomized, double-blind, placebo-controlled trial design

Official Title
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A Phase I Clinical Study Evaluating the Safety, Tolerability and Pharmacokinetics of HSK21542 in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: HSK21542
* Drug: HSK21542
* Drug: HSK21542
* Drug: HSK21542
* Drug: HSK21542
* Drug: HSK21542
* Drug: HSK21542
* Drug: HSK21542
* Drug: HSK21542


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 18-45 years old (inclusive) at screening; Male volunteers no less than 50 kg, or female volunteers no less than 45 kg, with body mass index [BMI] in the range of 18.0-27.0 kg/m2 (inclusive) at screening; Healthy volunteers, as assessed by the investigator based on past medical history, comprehensive physical examination, vital signs, and specified tests and examinations. Fully understand the nature, purpose, and potential benefits, inconveniences and risks of the trial. Understand the study procedure and voluntarily provide written informed consent. Able to communicate with the investigator and to follow all requirements of the study, and willing to be admitted into the phase I clinical facility. Exclusion Criteria: Those who have suffered or are currently suffering from any clinical serious disease such as circulatory system, endocrine system, nervous system, digestive system, respiratory system, hematology, immunology, psychiatry and metabolic abnormality or any other disease or physiological condition that can interfere with the results; Physical examination, vital sign monitoring, ECG examination, chest anteroposterior and lateral radiographs, laboratory examination (including blood routine, urine routine, blood biochemistry, coagulation function, thyroid function, blood pregnancy (only for female subjects) during screening period, and the researcher judged that the abnormality had clinical significance; People with positive hepatitis B surface antigen, positive hepatitis C antibody, positive Treponema pallidum antibody, or positive AIDS virus antibody test; Patients with QTcF>450 ms in ECG examination during screening; Allergic constitution: such as those who are allergic to two or more drugs and foods; Or those who are allergic to any ingredient in this product and auxiliary materials; (Auxiliary materials: glacial acetic acid, sodium acetate, water for injection) Those who cannot tolerate venipuncture and/or have a history of blood and needle sickness; Those who have drunk too much tea, grapefruit, coffee, caffeinated or grapefruit drinks for a long time (more than 8 cups a day, 1 cup=250mL); Those who have a history of alcohol abuse within 3 months before screening, that is, those who drink more than 14 units of alcohol per week (1 unit=12 ounces or 360 mL of beer, 1.5 ounces or 45 mL of spirits with 40% alcohol content, 5 ounces or 150 mL of wine), or those who have positive alcohol breath test; Volunteers with a positive urine nicotine test; Volunteers with drug abuse or dependence, or with a positive urine drugs of abuse test; Those who have used any prescription medicine, over-the-counter medicine, Chinese herbal medicine and health care products within 14 days Blood donation or loss of blood > 450 mL within the past 3 months; Participation in any clinical trials within the past 3 months; Volunteers who plan to become pregnant within the next 6 months; Any other factors judged by the investigator to be unsuitable for participating in this study.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSK21542 0.2 μg/kg（15 min)<br>Healthy volunteers 0.2 μg/kg HSK21542 | Drug: HSK21542<br>* Intravenous injection 0.2 μg/kg solution (active or placebo, 0.5-1h after standard meal). Complete infusion within 15 min.<br>* Other names: HSK21542 0.2 μg/kg;|
| Experimental: HSK21542 0.5 μg/kg<br>Healthy volunteers 0.5 μg/kg HSK21542 or Placebo | Drug: HSK21542<br>* Intravenous injection 0.5 μg/kg solution (active or placebo, 0.5-1h after standard meal). Complete infusion within 15 min.<br>* Other names: HSK21542 0.5 μg/kg;|
| Experimental: HSK21542 1 μg/kg （15min)<br>Healthy volunteers 1 μg/kg HSK21542 or Placebo | Drug: HSK21542<br>* Intravenous injection 1 μg/kg solution (active or placebo, 0.5-1h after standard meal). Complete infusion within 15 min.<br>* Other names: HSK21542 1 μg/kg;|
| Experimental: HSK21542 1 μg/kg （2min)<br>Healthy volunteers 1 μg/kg HSK21542 or Placebo | Drug: HSK21542<br>* Intravenous injection 1 μg/kg solution (active or placebo, 0.5-1h after standard meal). Complete infusion within 2 min.<br>* Other names: HSK21542 1 μg/kg;|
| Experimental: HSK21542 0.75 μg/kg<br>Healthy volunteers 0.75 μg/kg HSK21542 or Placebo | Drug: HSK21542<br>* Intravenous injection 0.75 μg/kg solution (active or placebo, 0.5-1h after standard meal). Complete infusion within 15 min.<br>* Other names: HSK21542 0.75 μg/kg;|
| Experimental: HSK21542 1.5 μg/kg<br>Healthy volunteers 1.5 μg/kg HSK21542 or Placebo | Drug: HSK21542<br>* Intravenous injection 1.5 μg/kg solution (active or placebo, 0.5-1h after standard meal). Complete infusion within 15 min.<br>* Other names: HSK21542 1.5 μg/kg;|
| Experimental: HSK21542 2.25 μg/kg<br>Healthy volunteers 2.25 μg/kg HSK21542 or Placebo | Drug: HSK21542<br>* Intravenous injection 2.25 μg/kg solution (active or placebo, 0.5-1h after standard meal). Complete infusion within 15 min.<br>* Other names: HSK21542 2.25 μg/kg;|
| Experimental: HSK21542 3.375 μg/kg<br>Healthy volunteers 3.375 μg/kg HSK21542 or Placebo | Drug: HSK21542<br>* Intravenous injection 3.375 μg/kg solution (active or placebo, 0.5-1h after standard meal). Complete infusion within 15 min.<br>* Other names: HSK21542 3.375 μg/kg;|
| Experimental: HSK21542 0.2 μg/kg（2min)<br>Healthy volunteers 0.2 μg/kg HSK21542 or Placebo | Drug: HSK21542<br>* Intravenous injection 0.2 μg/kg solution (active or placebo, 0.5-1h after standard meal). Complete infusion within 2 min.<br>* Other names: HSK21542 0.2 μg/kg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AE/serious AE | Adverse event/serious adverse event | From screening up to 3 weeks | 
| Vital signs: Systolic and Diastolic Blood Pressure | Vital signs (Systolic and Diastolic Blood Pressure) will be collected in healthy volunteers. | From screening up to 3 weeks | 
| Ramsay sedation score | Ramsay sedation score will be collected | -60 minutes before administration until 24 hours after administration | 
| Visual analog scale (VAS) addiction score | VAS addiction score will be collected | from administration to 24 hours after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak concentration (Cmax) | Cmax（a measure of the body's exposure to HSK21542）will be calculated in healthy volunteers. | -30 minutes before administration until 24 hours after administration | 
| Area under the concentration-time curve（AUC） | AUC（a measure of the body's exposure to HSK21542）will be calculated in healthy volunteers. | -30 minutes before administration until 24 hours after administration | 
| Tmax | time to peak observed | -30 minutes before administration until 24 hours after administration | 
| Total clearance | Total clearance | -30 minutes before administration until 24 hours after administration | 
| Prolactin level | Prolactin level will be collected | before administration until 24 hours after administration | 
| Antidiuretic hormone level | Antidiuretic hormone level will be collected | before administration until 24 hours after administration | 
| Urine volume | Urine volume will be collected | before administration until 24 hours after administration |