This is the first clinical trial of HSK3486 and will be conducted in healthy volunteers to determine the safety, tolerability (including pain on injection), and PK(only to be assessed for subjects who are randomized to HSK3486 in Cohorts 3 to 8)and PD and profiles of HSK3486 administered as a single IV injection.

Results from this study will supports further clinical development of HSK3486. This study will be performed in compliance with the protocol, International Conference on Harmonization Good Clinical Practice (ICH GCP) and local regulatory requirements. Aspects of the study concerned with the investigational product will meet the requirements of Good Manufacturing Practice (GMP).

Inclusion Criteria:

• Male, aged 18 - 49 years (inclusive).
• In general good health without clinically significant (CS) medical history.
• American Society of Anesthesiologists (ASA) Physical Status Classification of I or II.
• Body Mass Index (BMI) between 18 and 30 kg/m2 (inclusive).
• Negative screen for drugs of abuse, alcohol, Hepatitis B surface antigen (HBs-Ag), Hepatitis C Virus antibody (HCV-Ab) and Human Immunodeficiency Virus (HIV) at screening; and drugs of abuse, alcohol pre dose on Day -1.
• Normal or non-clinically significant (NCS) findings on a physical examination, 12-lead electrocardiogram (ECG) and vital signs (respiration rate between 12 and 20 breaths per minute, blood pressure between 100-140/60-90 mmHg, heart rate between 50-99 beats per minute, temperature between 35.8°C and 37.5°C and pulse oximetry values > 95% on room air).
• Clinical laboratory values within the normal limits as defined by the clinical laboratory samples, unless the Principal Investigator (PI) decided that out-of-range values were not CS.
• Able to provide written informed consent.
• Willing and able to follow study instructions and likely to complete all study requirements.
• Suitable venous and arterial access.

Exclusion Criteria:

• History of allergy or sensitivity to: propofol, components of Fresofol 1% MCT/LCT propofol, or HSK3486 (excipients soy bean oil, glycerine, triglycerides, purified egg phospholipids, sodium oleate and sodium hydroxide), or plain lignocaine.
• History of CS problems with general anesthesia.
• Current smoker, or a history of regular (more than weekly) use of tobacco- or nicotine-containing products within 2 months prior to screening.
• History of excessive alcohol intake (more than four standard drinks daily, on average) or use of recreational drugs within the last 3 months.
• Use of prescription or over the counter medications within 7 days of Investigational Product administration, with the exception of simple analgesics such as paracetamol and oral non-steroidal antiinflammatory agents.
• Standard donation of blood within 30 days of the study.
• Donation of plasma or participation in a plasmapheresis program within 7 days preceding this study.
• Receipt of any investigational study drug within 30 days prior to screening.
• Unable to fast for the 6 hours prior to Investigational Product administration.
• Clinically significant (as judged by the Investigator) presence of acute illness (e.g. gastrointestinal illness, infection such as influenza, upper respiratory tract infection) at admission to the clinical study unit.
• Anticipated need for surgery or hospitalization during the study.
• Anatomical abnormality that would potentially interfere with airway management under unconscious sedation or anesthesia.

Following Screening, subjects who meet the inclusion/exclusion criteria will be assigned a subject number in the order in which they are enrolled in the study. The subject number will determine the allocation of treatment as per the randomization list which will be generated by INCResearch Australia Pty Ltd and provided to the pharmacist. Cohorts 1 and 2 are a placebo controlled design, with open-labelling for the sentinel subjects and double-blind thereafter. Cohorts 3 to 8 are an open-label, positive controlled design.