Safety and Pharmacokinetics/Pharmacodynamics of HSK3486 in Healthy Elderly Subjects

NCT04197661 | Completed Phase 1 DMC

• 1 other identifier: HSK3486-108
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Elderly Subjects

Keywords

Healthy Elderly Subjects

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• MOAA/S(modified observer's assessment of alert /sedation)

  -5 minutes before administration until 1 hours post administration on day 1

• Bispectral index(BIS)

  -5 minutes before administration until 1 hours post administration on day 1

• Tmax

  -30 minutes before administration until 24 hours post administration on day 1

• Total clearance

  -30 minutes before administration until 24 hours post administration on day 1

• blood pressure（systolic, diastolic and mean arterial pressure）

  from the screening to 2 days post-dose

Study Arms (4)

Elderly groupⅠ

ACTIVE COMPARATOR

Elderly groupⅠ 65 years or older 0.2 mg/kg HSK3486

Drug: HSK3486

Elderly group Ⅱ

ACTIVE COMPARATOR

Elderly group Ⅱ 65 years or older 0.3 mg/kg HSK3486

Drug: HSK3486

Elderly group Ⅲ

ACTIVE COMPARATOR

Elderly group Ⅲ 65 years or older 0.4 mg/kg HSK3486

Drug: HSK3486

Non-elderly group IV

ACTIVE COMPARATOR

Non-elderly group IV 18 to 64 years 0.4 mg/kg HSK3486

Drug: HSK3486

Interventions

HSK3486 DRUG

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

Also known as: HSK3486 0.2 mg/kg

Elderly groupⅠ

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sichuan Haisco Pharmaceutical Group Co., Ltd: lead
• The First Hospital of Jilin University: collaborator

Study Sites (1)

Phase I Clinical Trial Laboratory, The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Related Publications (1)

• 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.

  PMID: 28430430 RESULT

MeSH Terms

Interventions

HSK3486

Study Officials

• Yanhua Ding, PhD

  Phase I Clinical Trial Laboratory，The First Hospital of Jilin University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2019
• First Posted: December 13, 2019
• Study Start: December 25, 2019
• Primary Completion: January 22, 2020
• Study Completion: May 22, 2020
• Last Updated: December 17, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)