A Phase IIa Study Investigating the Tolerance, Efficacy and Safety of HSK3486

Study Overview
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Brief Summary
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This is a Phase IIa, open-label, propofol-controlled ,dose-escalation, multi-center Study to evaluate the tolerance, efficacy and safety of HSK3486 for induction of general anesthesia in elective surgery patients.This study is consisted of two cohorts, dose-escalation and dose-expansion cohorts. The doses in dose- expansion cohort were selected from dose-escalation results.

Official Title
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A Phase IIa, Open-label, Propofol-controlled ,Dose-escalation, Multi-center Study to Evaluate the Tolerance, Efficacy and Safety of HSK3486 for Induction of General Anesthesia in Elective Surgery Patients.

Conditions
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Induction of General Anaesthesia

Intervention / Treatment
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* Drug: HSK3486
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inpatients required tracheal intubation under general anesthesia and a non-emergency non-cardiothoracic and non-extracranial elective surgery for an estimated duration of ≤ 3 h ;. Males or females, aged ≥ 18 and ≤ 65 years old; Body mass index (BMI) ≥ 19 and ≤ 30 kg/m2; ASA grade I II; Capable of understanding the procedure and method of this study, willing to sign an informed consent form and to complete this study in strict accordance with the study protocol. Exclusion Criteria: Patients were contraindicated in general anesthesia.; Patients with a known sensitivity to propofol, opioids, naloxone, eggs, soy products or a medical condition such that these agents were contraindicated Patients in receipt of any investigational drug within 30 days before screening. Patients in receipt of propofol, opioid , other sedative or anesthetic or analgesics within one month prior to the screening period. Patients in receipt of general anesthesia surgery within two weeks prior to the screening period. The patient has some history or evidence of increased risk of sedation or anesthesia, such as cardiovascular disease, respiratory disease, cerebrovascular disease, liver, kidney, blood system, or metabolic system disease prior to the screening period. Abnormal laboratory results consisting of any of the following: : 1) AST and ALT≥ 2×ULN； 2）TBIL≥ 1.5×ULN； 3）Hb≤ 90g/L; 4）ANC≤1.5×109/L; 5) PLT≤80×109/L； 6） serum creatinine≥ 1.5×ULN. 8. Patients with a history of drug or ethanol abuse with the past 3 months. 9. Pregnant women or female patients with a positive serum or urine human chorionic gonadotropin pregnancy test at screening or baseline or lactating female patients. . 10. 10. Patients with a positive Allen 's test who collected arterial blood for PK study. 11. Patients with respiratory management difficulties. 12. Patients with an inability to communicate well with the investigator, or deemed unsuitable according to the investigator (in each case providing a reason).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSK3486<br>Dose Escalation Cohort: 0.1 mg/kg, 0.2 mg/kg, 0.3mg/kg 0.4 mg/kg 0.5 mg/kg, 0.6 mg/kg, 0.7mg/kg, 0.8 mg/kg Dose Expansion Cohort: 0.3 mg/kg and 0.5 mg/kg. | Drug: HSK3486<br>* For induction of general anesthesia In dose escalation cohort: Starting from 0.4mg/kg, up-titration dose by 0.1mg/kg until 0.8mg//kg or down-titration dose by 0.1mg/kg until 0.1mg/kg based on the efficacy and safety results.<br>|
| Active Comparator: Propofol<br>Dose Escalation Cohorts:2.0mg/kg and 2.5mg/kg; Dose Expansion Cohorts: 2.0mg/kg | Drug: Propofol<br>* For induction of general anesthesia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The success rate of induction of general anesthesia | To find the MTD or the RP2D of HSK3486 in the induction of general anesthesia, the success rate of induction of general anesthesia is the primary outcome measurement. | during induction of general anesthesia on day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from start of IMP administration to loss of eyelash reflex |  | during induction of general anesthesia on day 1 | 
| Time from start of IMP administration to loss of consciousness |  | during induction of general anesthesia on day 1 | 
| Time from start of IMP administration to intubation and the intubation reaction |  | during induction of general anesthesia on day 1 | 
| Mini-Mental State Examination (MMSE) total scores(0-30) by time point | Change from baseline in Mini-Mental State Examination (MMSE) total score | Pre-dose to 48 hours post-dose | 
| change from baseline in blood pressure （systolic, diastolic and mean arterial pressure) | safety endpoits | pre-dose to 20 minutes post-dose | 
| change from baseline in heart rate | safety endpoits | pre-dose to 20 minutes post-dose | 
| change from baseline in arterial oxygen saturation | safety endpoits | pre-dose to 20 minutes post-dose | 
| Number of patients with adverse events | safety endpoits | Pre-dose to 48 hours post-dose |