This is a Phase I, randomized, subject-blinded, placebo controlled study to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD),and food effect (FE) of HSK44459 following (1) a single ascending dose (part 1), (2) 10 days of multiple ascending dose (part 2), and (3) a single dose two-period crossover FE cohort.

Inclusion Criteria:

1. Voluntarily sign the informed consent form, understand the trialprocedures, and be willing to comply with all trial procedures andrestrictions;
2. 18 years to 55 years (inclusive), male and female;
3. Male subjects weight ≥50 kg and female subjects weight ≥45 kg. Bodymass index (BMI) : 19-26 kg/m2 (inclusive) ;
4. Subjects are willing to voluntarily use effectivecontraceptives from screening to at least 3 months after the last dose administration.

Exclusion Criteria:

1. Have a history of severe and uncontrolled diseases, such ascardiovascular, respiratory, liver, gastrointestinal, endocrine,hematologic, mental/nervous systems diseases within 3 months prior to screening;
2. Have an infection that requires systematic treatment with antibiotics, antifungal, antiparasitic or antiviral drugs;
3. Have a history of any malignant tumors;
4. The abnormalities were clinically significant during the screening period, such as physical examination, vital signs, blood biochemistry, blood routine, coagulation, urine routine, blood pregnancy test, infectious diseases and X-ray;
5. Subjects whose results of routine 12-lead electrocardiograms were inconsistent with normal heart conduction and function;
6. Previous or current gastrointestinal, liver, kidney, or other disease known to interfere with drug absorption, distribution, metabolism, or excretion;
7. Smoking more than 5 cigarettes per day within 3 months prior toscreening or smoking during the study;
8. Average alcohol intake is more than 14 unit per week (1unit=10g alcohol , 1 unit=285 mL 4.9% alcohol beer, or 30 mL 40% alcohol spirit, or 100mL 12% alcohol wine) within the 3 months prior to screening, or positive urine drug screen at screening;
9. Have a history of high consumption of grapefruit juice, methylxanthinerich food or beverage (such as coffee, tea, cola, chocolate, energydrinks) ,consumption of grapefruit juice;
10. Blood donation (or blood loss) ≥400 mL, or receiving blood products to improve anemia within 3 months prior to the screening;
11. Subjects who have a allergic to any component of HSK44459 or allergic history to opiates;
12. Have participated in any clinical investigator within 3 months prior to screening;
13. A pregnant/lactating woman, or has a positive pregnancy test at screening or during the trial;
14. Not suitable for this study as judged by the investigator.