Safety and Pharmacokinetics/Pharmacodynamics of HSK3486 in Healthy Elderly Subjects

Phase 1

Completed

• Conditions: Healthy Elderly Subjects
• Interventions: Drug: HSK3486

• Registration Number: NCT04197661
• Lead Sponsor: Sichuan Haisco Pharmaceutical Group Co., Ltd

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-06
• Study First Submitted QC: 2019-12-10
• Study First Posted: 2019-12-13
• Study Start: 2019-12-25
• Primary Completion: 2020-01-22
• Study Completion: 2020-05-22
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-16
• Last Update Posted: 2020-12-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Sign the informed consent form and fully understand the content, procedure and possible adverse effects before the trial starts;
2. Able to complete the study in compliance with the requirements of the clinical trial protocol;
3. 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;
4. 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));
5. 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);
6. 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

1. Smoke more than 5 cigarettes per day on average within 3 months prior to screening;
2. Patient having contraindications to deep sedation/general anesthesia or a history of past sedation/anesthesia accidents;
3. 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);
4. History of drug abuse or any signs of long-term use of benzodiazepines (such as insomnia, anxiety, spasms) within 3 months prior to screening;
5. 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);
6. 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);
7. Subjects judged by the investigator to be unsuitable for participating in this trial for any reason.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Elderly groupⅠ	HSK3486	Elderly groupⅠ 65 years or older 0.2 mg/kg HSK3486
Elderly group Ⅲ	HSK3486	Elderly group Ⅲ 65 years or older 0.4 mg/kg HSK3486
Elderly group Ⅱ	HSK3486	Elderly group Ⅱ 65 years or older 0.3 mg/kg HSK3486
Non-elderly group IV	HSK3486	Non-elderly group IV 18 to 64 years 0.4 mg/kg HSK3486

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Phase I Clinical Trial Laboratory, The First Hospital of Jilin University; 🇨🇳 Chang chun, Ji Lin, China