HSK16149 for Perioperative Analgesia in Orthopedic Surgery

Study Overview
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Brief Summary
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This study will compare the effect and safety of HSK16149 with placebo on perioperative analgesia in orthopedic surgery, and explore the dosage of HSK16149 capsules for orthopedic analgesia during perioperative period.

Detailed Description
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This study included patients who have orthopedic surgery under general anesthetic, with expected operation time ≤4h. Subjects were given 40mg or 60mg of HSK16149 or placebo orally the night before surgery, 2h before surgery, 4h and 16h after surgery, for a total of 4 times during the whole treatment period. Subjects will receive intravenous patient-controlled analgesia (PCA) morphine for pain in the immediate postoperative period. If PCA is insufficient, rescue analgesia of morphine may be given I.V. as determined by the investigator. After the treatment period, the subjects will be followed up.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-controlled Phase II Study of The Efficacy And Safety of HSK16149 In The Treatment of Patients With Orthopedic Perioperative Analgesia

Conditions
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Post-operative Pain

Intervention / Treatment
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* Drug: HSK16149 capsule
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between the ages of 18 and 75 years (included); Elective orthopedic surgery under general anesthesia, expected operation time ≤4 hours and postoperative morphine analgesia time ≥24 hours; 18kg/m^2≤BMI≤30 kg/m^2; American Society of Anesthesiologists (ASA) grade I and II; Exclusion Criteria: Any of the following medical histories or conditions prior to screening: Long history of chronic pain; history of severe cardiovascular or respiratory disease; history of neurological or psychiatric disorders; history of acute poisoning with alcohol, hypnotics, analgesics or other drugs acting on the central nervous system; major surgery within 3 months; patients with high bleeding risk; history of renal disease treated with dialysis within 28 days before surgery; have active infection within the past 2 weeks; Use of any of the following medications or treatments: opioid analgesics for more than 10 consecutive days within 3 months prior to screening; other analgesics before randomization if the last dose was taken less than 5 half-lives of the drug (according to the label); Abnormal laboratory tests during screening: Hypertension that is not adequately controlled by antihypertensive drugs (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), or systolic blood pressure ≤90 mmHg during screening; A history of drug abuse, and/or alcohol abuse in the 3 months prior to screening; Participated in another clinical trial and received IMP within 30 days prior to screening; Pregnant or lactating women; Unwillingness to use reliable contraceptive methods from the time of screening until 28 days after the last dose of IMP;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preoperative administration of HSK16149 40mg<br>HSK16149 40mg will be administered the night before and 2h before surgery | Drug: HSK16149 capsule<br>* Subjects will be given 40mg or 60mg of HSK16149 orally.<br>* Other names: HSK16149;|
| Experimental: Preoperative administration of HSK16149 60mg<br>HSK16149 60mg will be administered the night before and 2h before surgery | Drug: HSK16149 capsule<br>* Subjects will be given 40mg or 60mg of HSK16149 orally.<br>* Other names: HSK16149;|
| Experimental: Preoperative and postoperative administration of HSK16149 40mg<br>HSK16149 40mg will be administered orally the night before surgery, 2h before surgery, 4h and 16h after surgery | Drug: HSK16149 capsule<br>* Subjects will be given 40mg or 60mg of HSK16149 orally.<br>* Other names: HSK16149;|
| Experimental: Preoperative and postoperative administration of HSK16149 60mg<br>HSK16149 60mg will be administered orally the night before surgery, 2h before surgery, 4h and 16h after surgery | Drug: HSK16149 capsule<br>* Subjects will be given 40mg or 60mg of HSK16149 orally.<br>* Other names: HSK16149;|
| Placebo Comparator: placebo<br>The placebo will be administered orally the night before surgery, 2h before surgery, 4h and 16h after surgery | Drug: Placebo<br>* Subjects will be given HSK16149 placebo orally.<br>* Other names: HSK16149 placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morphine Consumption | IV Patient Controlled Analgesia (PCA) morphine for pain management in the immediate postoperative period for an average of 24 hours after surgery. If PCA is insufficient, rescue analgesia of morphine may be given I.V. as determined by the investigator. Total morphine consumption = PCA morphine consumption + rescue analgesia morphine consumption. | Participants received PCA pump, an average of 24 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NRS at rest and during exercise | NRS:0 (no pain) to 10 (worst possible pain) | 1, 2, 6, 12, 18, and 24 hours after surgery | 
| Time of first rescue analgesia with morphine after surgery |  | Within 24 hours after surgery | 
| Incidence of adverse reactions associated with morphine |  | Within 24 hours after surgery | 
| The frequency of rescue analgesia with morphine |  | Within 24 hours after surgery | 
| The total number of PCA presses and the number of effective PCA presses |  | Within 24 hours after surgery | 
| Daily Sleep Interference Scale (DSIS) | Subjects review their sleep status during the past 12 hours at 8:00 a.m. on the day of surgery. DSIS: 0 (not affecting sleep) to 10 (unable to sleep) | Within 24 hours after surgery | 
| Subjects analgesic satisfaction score | Analgesic satisfaction score: 0 (not satisfied) to 10 (very satisfied) | Within 24 hours after surgery | 
| Investigators analgesic satisfaction score | Analgesic satisfaction score: 0 (not satisfied) to 10 (very satisfied) | Within 24 hours after surgery | 
| Number of participants with treatment-related adverse events(TEAE) as assessed by CTCAE v5.0. | Number and severity of AEs, clinical laboratory abnormalities, physical examinations, 12-lead electrocardiograms (ECGs)(including QT Interval,QTc Interval and PR Interval), and vital signs. | From enrollment to 72 hours after surgery |