Safety and Pharmacokinetics/Pharmacodynamics of HSK3486 in Healthy Elderly Subjects

Study Overview
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Brief Summary
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It is a single-center, open-label, dose-finding, Phase I clinical study evaluating the pharmacokinetics, pharmacodynamics, and safety characteristics of HSK3486 in healthy elderly subjects.

Official Title
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A Study Evaluating Pharmacokinetics, Pharmacodynamics and Safety of Intravenous Administration of HSK3486 Injectable Emulsion in Healthy Elderly Subjects

Conditions
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Healthy Elderly Subjects

Intervention / Treatment
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* Drug: HSK3486
* Drug: HSK3486
* Drug: HSK3486
* Drug: HSK3486


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent form and fully understand the content, procedure and possible adverse effects before the trial starts; Able to complete the study in compliance with the requirements of the clinical trial protocol; Subjects (including their partners) are willing to voluntarily adopt an effective measure of contraception starting from screening to 6 months after the last dose of the investigational drug. See the attachment for specific contraceptive measures; Males and females with full capacity for civil conduct, aged ≥ 18 years old (aged between 18 and 64 years old for the non-elderly group and ≥ 65 years old for the elderly group (inclusive)); Females weighing ≥ 45 kg and males weighing ≥ 50 kg, and with a body mass index (BMI) of ≥ 18 and ≤ 30 kg/m2 (BMI = Weight (kg)/height2(m2))(inclusive); For all subjects, the body temperature should be between 35.9-37.6 °C, respiratory rate between 12-20 breaths/min, and SpO2 when inhaling > 95%; in addition, for subjects in the non-elderly group, the blood pressure should be between 90-140/60-90 mmHg and heart rate between 60-99 bpm; for those in the elderly group, the blood pressure should be between 90-160/60-100 mmHg and heart rate between 50-100 bpm; Exclusion Criteria: Smoke more than 5 cigarettes per day on average within 3 months prior to screening; Patient having contraindications to deep sedation/general anesthesia or a history of past sedation/anesthesia accidents; Known sensitivity to HSK3486 excipients (soybean oil, glycerin, triglyceride, egg lecithin, sodium oleate, and sodium hydroxide); or history of drug allergies (including other anesthetics), allergic diseases, or those with hyperactive immuneresponse(allergies to various drugs and foods); History of drug abuse or any signs of long-term use of benzodiazepines (such as insomnia, anxiety, spasms) within 3 months prior to screening; Acute diseases with clinical significance (determined by the investigator) within 2 weeks prior to screening, including GI diseases and infections (such as respiratory or CNS infections); History or evidence of cardiovascular diseases prior to screening: Uncontrolled hypertension [SBP ≥ 170 mmHg and/or DBP ≥ 105 mmHg without antihypertensive treatment, or SBP > 160 mmHg and/or DBP > 100 mmHg despite antihypertensive treatment], postural hypotension, severe arrhythmia, heart failure, Adams-Stokes syndrome, unstable angina, myocardial infarction within 6 months before screening, history of tachycardia/bradycardia requiring medication, II-III degree atrioventricular block (excluding patients with pacemakers), or QTcF interval ≥ 450 ms (Fridericia's correction formula); Subjects judged by the investigator to be unsuitable for participating in this trial for any reason.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Elderly groupⅠ<br>Elderly groupⅠ 65 years or older 0.2 mg/kg HSK3486 | Drug: HSK3486<br>* Intravenously infuse 0.2 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.<br>* Other names: HSK3486 0.2 mg/kg;|
| Active Comparator: Elderly group Ⅱ<br>Elderly group Ⅱ 65 years or older 0.3 mg/kg HSK3486 | Drug: HSK3486<br>* Intravenously infuse 0.3 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.<br>* Other names: HSK3486 0.3 mg/kg;|
| Active Comparator: Elderly group Ⅲ<br>Elderly group Ⅲ 65 years or older 0.4 mg/kg HSK3486 | Drug: HSK3486<br>* Intravenously infuse 0.4 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.<br>* Other names: HSK3486 0.4 mg/kg;|
| Active Comparator: Non-elderly group IV<br>Non-elderly group IV 18 to 64 years 0.4 mg/kg HSK3486 | Drug: HSK3486<br>* Intravenously infuse 0.4 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.<br>* Other names: HSK3486 0.4 mg/kg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak concentration (Cmax) | Cmax（a measure of the body's exposure to HSK3486）will be compared between non-elderly subjects and elderly subjects. | -30 minutes before administration until 24 hours post administration on day 1 | 
| Area under the concentration-time curve（AUC） | AUC（a measure of the body's exposure to HSK3486）will be compared between non-elderly subjects and elderly subjects. | -30 minutes before administration until 24 hours post administration on day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MOAA/S(modified observer's assessment of alert /sedation) | modified observer's assessment of alert /sedation | -5 minutes before administration until 1 hours post administration on day 1 | 
| Bispectral index(BIS) | Bispectral index | -5 minutes before administration until 1 hours post administration on day 1 | 
| Tmax | time to peak observed | -30 minutes before administration until 24 hours post administration on day 1 | 
| Total clearance | Total clearance | -30 minutes before administration until 24 hours post administration on day 1 | 
| blood pressure（systolic, diastolic and mean arterial pressure） | safety endpoits | from the screening to 2 days post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Elderly Subjects