Efficacy and Safety of HSK3486 Compared to Propofol for Adults Undergoing Elective Surgery With General Anesthesia

Inclusion Criteria

• 1. Subjects undergoing elective surgery (non emergency, non cardiothoracic, and non intracranial surgery, anticipated to last at least 1 hour) requiring endotracheal intubation and inhalation general anesthesia during the maintenance period. Duration of surgery is defined as time from study drug administration to time of transfer from operating room to recovery room or PACU.
• Males or females, aged ≥18 years old, with ASA-PS I to IV (Appendix 6). For ASA-PS IV subjects, clinical status must be optimized at time of preoperative anesthesia evaluation per judgement of the anesthesiologist.
• BMI ≥18 kg/m2. 4. Vital signs at screening: RR ≥10 and ≤24 breaths/min; SpO2≥92% in ambient air; SBP ≥90 and ≤160 mmHg; DBP ≥55 and ≤100 mmHg; HR ≥55 (or ≥50 if subjects are on beta blockers) and ≤100 beats/min.
• For all women of childbearing potential, negative serum pregnancy test at screening and must have negative urine pregnancy test at baseline (Day 1). Additionally, women of childbearing potential* must agree to use effective contraception as defined in 7.3.4 from the time of consent until 30 days post study drug administration.
• Capable of understanding the procedures and methods of this study, willing to sign an Informed Consent Form, and able to complete this study in strict compliance with the study protocol.
• Willing to comply with the site's COVID guidelines and testing requirements as applicable.
• Patients with psychiatric/mental disorders must be considered stable on treatment (e.g., SSRIs, SNRIs, TCAs, MAOIs, psychotherapy) and no hospitalizations and urgent care for at least 1 year.

*Women NOT of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral salpingo-oophorectomy) or who are postmenopausal (defined 12 months since last regular menses).

Exclusion criteria

• Contraindications to deep sedation/general anesthesia or a history of adverse reaction to sedation/general anesthesia.
• Known to be allergic to eggs, soy products, opioids and their antidotes, or propofol; subject having contraindications to propofol, opioids, and their antidotes.
• Medical condition or evidence of increased sedation/general anesthesia risk as follows:
• Cardiovascular disorders: uncontrolled hypertension (SBP>160 mmHg and/or DBP >100 mmHg) with or without antihypertensive therapy (antihypertensive therapy should be stable for 1 month prior to screening), serious arrhythmia (including the subjects with implanted pace makers), unstable heart failure, Adams-Stokes syndrome (i.e., syncope or near syncope due to cardiac arrythmia), unstable angina, myocardial infarction occurring within 6 months prior to screening, history of tachycardia/bradycardia requiring medications, third degree atrioventricular block or QT interval corrected for HR using Fridericia's formula (QTcF)≥450ms for males and ≥470ms for females.
• History of severe obstructive lung disease (i.e., forced expiratory volume in 1 second [FEV1] 2 units (1 unit = 360 mL of beer or 45 mL of spirit with a strength of 40% or 150 mL of wine).
• History of drug abuse that, in the opinion of the investigator, may confound the interpretation of safety or efficacy in a study subject.
• Management risks of respiratory tract and judged by the investigator to be unsuitable for inclusion in the study as follows:
• Asthma must be stable: stable doses of asthma medications for the past 6 months, no requirement for rescue inhalers or oral steroids within past 6 months, not evaluated in emergency department, urgent care, or hospitalized for an asthma attack within past 1 year.
• History (or family history) of malignant hyperthermia.
• Any previous failure of tracheal intubation.
• Judged to have a difficult airway for endotracheal intubation in the opinion of the Investigator based on parameters such as modified Mallampati score (Grade III or IV [Appendix 7], neck mobility, short thyromental distance,