Safety and Pharmacokinetics/Pharmacodynamics of HSK3486 in Healthy Elderly Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Elderly Subjects
• Intervention / Treatment: Drug: HSK3486; Drug: HSK3486; Drug: HSK3486

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Ji Lin
    • Chang chun, Ji Lin, China, 130021
      • Phase I Clinical Trial Laboratory, The First Hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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
Tmax	time to peak observed	-30 minutes before administration until 24 hours post administration on day 1
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
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

Collaborators and Investigators

• Sponsor: Sichuan Haisco Pharmaceutical Group Co., Ltd
• Collaborators: The First Hospital of Jilin University
• Investigators: Study Director: Yanhua Ding, PhD, Phase I Clinical Trial Laboratory，The First Hospital of Jilin University

Publications and helpful links

General Publications

• Qin L, Ren L, Wan S, Liu G, Luo X, Liu Z, Li F, Yu Y, Liu J, Wei Y. Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics. J Med Chem. 2017 May 11;60(9):3606-3617. doi: 10.1021/acs.jmedchem.7b00254. Epub 2017 Apr 28.

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2019
• Primary Completion (Actual): January 22, 2020
• Study Completion (Actual): May 22, 2020

Study Registration Dates

• First Submitted: December 6, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 13, 2019

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Healthy Elderly Subjects
• Other Study ID Numbers: HSK3486-108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No