Clinical trial NCT04197661: Safety and Pharmacokinetics/Pharmacodynamics of HSK3486 in Healthy Elderly Subjects
Official title: A Study Evaluating Pharmacokinetics, Pharmacodynamics and Safety of Intravenous Administration of HSK3486 Injectable Emulsion in Healthy Elderly Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Elderly Subjects
Keywords: Healthy Elderly Subjects
Lead sponsor: Haisco Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: The First Hospital of Jilin University
First posted: 2019-12-13
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Peak concentration (Cmax)
timeFrame: -30 minutes before administration until 24 hours post administration on day 1
measure: Area under the concentration-time curve（AUC）
timeFrame: -30 minutes before administration until 24 hours post administration on day 1
Secondary outcomes:
measure: MOAA/S(modified observer's assessment of alert /sedation)
timeFrame: -5 minutes before administration until 1 hours post administration on day 1
measure: Bispectral index(BIS)
timeFrame: -5 minutes before administration until 1 hours post administration on day 1
measure: Tmax
timeFrame: -30 minutes before administration until 24 hours post administration on day 1
measure: Total clearance
timeFrame: -30 minutes before administration until 24 hours post administration on day 1
measure: blood pressure（systolic, diastolic and mean arterial pressure）
timeFrame: from the screening to 2 days post-dose
Other outcomes:
Locations:
city: Chang chun
country: China
facility: Phase I Clinical Trial Laboratory, The First Hospital of Jilin University
state: Ji Lin
Study officials:
affiliation: Phase I Clinical Trial Laboratory，The First Hospital of Jilin University
name: Yanhua Ding, PhD
role: STUDY_DIRECTOR
References:
citation: 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.