HSK16149 for Perioperative Analgesia in Orthopedic Surgery

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

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.

Study Overview

• Status: Completed
• Conditions: Post-operative Pain
• Intervention / Treatment: Drug: HSK16149 capsule; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Sino-Japanese Friendship Hospital
  • Guangdong
    • Dongguan, Guangdong, China
      • Dongguan People's Hospital
    • Foshan, Guangdong, China
      • Foshan Fuxing Chancheng Hospital
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Jinan University
  • Guizhou
    • Guiyang, Guizhou, China
      • Affiliated Hospital of Guizhou Medical University
    • Guiyang, Guizhou, China
      • Beijing Jishuitan Hospital Guizhou Hospital
    • Zunyi, Guizhou, China
      • Zunyi University Affiliated Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Henan provincial people's hospital
  • Hubei
    • Wuhan, Hubei, China
      • Wuhan Central Hospital
    • Wuhan, Hubei, China
      • People's Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China
      • Xiangya Third Hospital of Central South University
    • Hengyang, Hunan, China
      • The First Affiliated Hospital of South China University
  • Jiangsu
    • Lianyungang, Jiangsu, China
      • Lianyungang First People's Hospital
    • Nanjing, Jiangsu, China
      • Nanjing First Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • Sichuan Provincial People's Hospital
    • Chengdu, Sichuan, China
      • Chengdu Second People's Hospital
    • Chengdu, Sichuan, China
      • Chengdu Third People's Hospital
    • Guangyuan, Sichuan, China
      • Guangyuan First People's Hospital
    • Mianyang, Sichuan, China
      • Mianyang Central Hospital
    • Yibin, Sichuan, China
      • Yibin Second People's Hospital
  • Yunnan
    • Kunming, Yunnan, China
      • The First People's Hospital of Yunnan Province

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female between the ages of 18 and 75 years (included);
2. Elective orthopedic surgery under general anesthesia, expected operation time ≤4 hours and postoperative morphine analgesia time ≥24 hours;
3. 18kg/m^2≤BMI≤30 kg/m^2;
4. American Society of Anesthesiologists (ASA) grade I and II;

Exclusion Criteria:

1. 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;

2. 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);
3. Abnormal laboratory tests during screening:
4. 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;
5. A history of drug abuse, and/or alcohol abuse in the 3 months prior to screening;
6. Participated in another clinical trial and received IMP within 30 days prior to screening;
7. Pregnant or lactating women;
8. Unwillingness to use reliable contraceptive methods from the time of screening until 28 days after the last dose of IMP;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2023
• Primary Completion (Actual): June 12, 2023
• Study Completion (Actual): July 5, 2023

Study Registration Dates

• First Submitted: March 5, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 23, 2023

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: HSK16149-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No