Safety and Pharmacokinetics/Pharmacodynamics of HSK3486 in Healthy Elderly Subjects

Healthy Elderly Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04197661
• Other study ID #: HSK3486-108
• Status: Completed
• Phase: Phase 1
• Start date: December 25, 2019
• Est. completion date: May 22, 2020

Study information

• Verified date: December 2020
• Source: Haisco Pharmaceutical Group Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: May 22, 2020
• Est. primary completion date: January 22, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Elderly Subjects

Intervention

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

Locations

Country	Name	City	State
China	Phase I Clinical Trial Laboratory, The First Hospital of Jilin University	Chang chun	Ji Lin

Sponsors (2)

Lead Sponsor	Collaborator
Sichuan Haisco Pharmaceutical Group Co., Ltd	First Hospital of Jilin University

Country where clinical trial is conducted

China, 

References & 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 20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Bispectral index(BIS)	Bispectral index	-5 minutes before administration until 1 hours post administration on day 1
Secondary	Tmax	time to peak observed	-30 minutes before administration until 24 hours post administration on day 1
Secondary	Total clearance	Total clearance	-30 minutes before administration until 24 hours post administration on day 1
Secondary	blood pressure(systolic, diastolic and mean arterial pressure)	safety endpoits	from the screening to 2 days post-dose