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 nonintracranial surgery, anticipated to last at least 1 hour) requiring endotrachealintubation and inhalation general anesthesia during the maintenance period. Durationof surgery is defined as time from study drug administration to time of transferfrom operating room to recovery room or PACU.

2. Males or females, aged ≥18 years old, with ASA-PS I to IV (Appendix 6). ForASA-PS IV subjects, clinical status must be optimized at time of preoperativeanesthesia evaluation per judgement of the anesthesiologist.

3. 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 ifsubjects are on beta blockers) and ≤100 beats/min.

4. For all women of childbearing potential, negative serum pregnancy test atscreening and must have negative urine pregnancy test at baseline (Day 1).Additionally, women of childbearing potential* must agree to use effectivecontraception as defined in 7.3.4 from the time of consent until 30 days post studydrug administration.

5. Capable of understanding the procedures and methods of this study, willing tosign an Informed Consent Form, and able to complete this study in strict compliancewith the study protocol.

6. Willing to comply with the site's COVID guidelines and testing requirements asapplicable.

7. Patients with psychiatric/mental disorders must be considered stable on treatment (e.g., SSRIs, SNRIs, TCAs, MAOIs, psychotherapy) and no hospitalizations and urgentcare for at least 1 year.

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

Exclusion criteria:

1. Contraindications to deep sedation/general anesthesia or a history of adversereaction to sedation/general anesthesia.

2. Known to be allergic to eggs, soy products, opioids and their antidotes, orpropofol; subject having contraindications to propofol, opioids, and theirantidotes.

3. Medical condition or evidence of increased sedation/general anesthesia risk asfollows:

4. Cardiovascular disorders: uncontrolled hypertension (SBP>160 mmHg and/or DBP >100 mmHg) with or without antihypertensive therapy (antihypertensive therapyshould be stable for 1 month prior to screening), serious arrhythmia (includingthe subjects with implanted pace makers), unstable heart failure, Adams-Stokessyndrome (i.e., syncope or near syncope due to cardiac arrythmia), unstableangina, myocardial infarction occurring within 6 months prior to screening,history of tachycardia/bradycardia requiring medications, third degreeatrioventricular block or QT interval corrected for HR using Fridericia'sformula (QTcF)≥450ms for males and ≥470ms for females.

5. History of severe obstructive lung disease (i.e., forced expiratory volume in 1second [FEV1] <50% predicted), history of bronchospasm requiring treatment in ahospital emergency room or hospitalization occurring within 3 months prior toscreening, developing acute respiratory tract infection within 2 weeks prior tobaseline (such as symptoms of fever, shortness of breath, wheezing, nasalcongestion, and cough).

6. Cerebrovascular disease: subject with a history of serious craniocerebralinjury, convulsion, seizure disorder, intracranial hypertension, cerebralaneurysm, or stroke.

7. Patients with psychiatric diseases (schizophrenia, mania) who have not been ona stable treatment regimen (with SSRIs, SNRIs, TCAs, MAOIs) for at least 1 yearor who have been hospitalized or had emergent/urgent care within the past year.

8. Uncontrolled clinically significant conditions of liver (e.g., severe hepaticinsufficiency defined as Childs-Pugh class C), kidney, gastrointestinal tract,blood system, nervous system, or metabolic system diseases, judged by theinvestigator to be unsuitable for involvement in the study.

9. Known glycosylated hemoglobin (HbA1c) greater than or equal to 10%.

10. Known thyroid-stimulating hormone (TSH) value 10% outside the normal range oron thyroid replacement therapy with a known free T-4 level outside the normalrange.

11. History of alcohol abuse within 3 months prior to screening, where alcoholabuse refers to daily alcohol drinking >2 units (1 unit = 360 mL of beer or 45mL of spirit with a strength of 40% or 150 mL of wine).

12. History of drug abuse that, in the opinion of the investigator, may confoundthe interpretation of safety or efficacy in a study subject.

13. Management risks of respiratory tract and judged by the investigator to beunsuitable for inclusion in the study as follows:

14. Asthma must be stable: stable doses of asthma medications for the past 6months, no requirement for rescue inhalers or oral steroids within past 6months, not evaluated in emergency department, urgent care, or hospitalized foran asthma attack within past 1 year.

15. History (or family history) of malignant hyperthermia.

16. Any previous failure of tracheal intubation.

17. Judged to have a difficult airway for endotracheal intubation in the opinion ofthe Investigator based on parameters such as modified Mallampati score (GradeIII or IV [Appendix 7], neck mobility, short thyromental distance, and/orhistory of difficult intubation).

18. Any medication that has the potential to interact synergistically with propofol orHSK3486, including but not limited to all sedatives and hypnotics (e.g.,benzodiazepines and opioids) taken within 5 half-lives prior to Day 1.

19. Laboratory parameters measured at screening with the following levels:

20. Neutrophil count ≤1.5 x 109/L

21. Platelet count <80 x 109/L

22. Hemoglobin <90 g/L (without blood transfusion within 14 days)

23. Alanine transaminase and/or aspartate transaminase ≥2.0 x upper limit of normal (ULN)

24. Total bilirubin ≥2.0 x ULN

25. Severe renal impairment defined by creatinine clearance (CrCl) ≤30 mL/min

26. Female subjects with a positive pregnancy test at screening (serum) or baseline (urine); lactating subjects; any subject planning to get pregnant within 1 monthafter the study (including the male subject's partner).

27. Judged by the investigator to have any other factors that make the subjectunsuitable for participation in the study.