Safety and Pharmacokinetics/Pharmacodynamics of HSK3486 in Healthy Elderly Subjects

Overview

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.

Full Title of Study: “A Study Evaluating Pharmacokinetics, Pharmacodynamics and Safety of Intravenous Administration of HSK3486 Injectable Emulsion in Healthy Elderly Subjects”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Other
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 28, 2020

Interventions

  • Drug: HSK3486
    • Intravenously infuse 0.2 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.
  • Drug: HSK3486
    • Intravenously infuse 0.3 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.
  • Drug: HSK3486
    • Intravenously infuse 0.4 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.
  • Drug: HSK3486
    • Intravenously infuse 0.4 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.

Arms, Groups and Cohorts

  • Active Comparator: Elderly groupⅠ
    • Elderly groupⅠ 65 years or older 0.2 mg/kg HSK3486
  • Active Comparator: Elderly group Ⅱ
    • Elderly group Ⅱ 65 years or older 0.3 mg/kg HSK3486
  • Active Comparator: Elderly group Ⅲ
    • Elderly group Ⅲ 65 years or older 0.4 mg/kg HSK3486
  • Active Comparator: Non-elderly group IV
    • Non-elderly group IV 18 to 64 years 0.4 mg/kg HSK3486

Clinical Trial Outcome Measures

Primary Measures

  • Peak concentration (Cmax)
    • Time Frame: -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)
    • Time Frame: -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 Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Sichuan Haisco Pharmaceutical Group Co., Ltd.
  • Collaborator
    • First Hospital of Jilin University
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Yanhua Ding, PhD, Study Director, Phase I Clinical Trial Laboratory,The First Hospital of Jilin University
  • Overall Contact(s)
    • Shi-ping Ma, PhD, (021)50799069, masp@haisco.com

Citations Reporting on Results

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.

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