A Trial of SHR0410 Injection in Postsurgical Pain Management

Study Overview
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Brief Summary
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The study is being conducted to evaluate the efficacy, safety of SHR0410 Injection and to explore the reasonable of SHR0410 Injection for Pain Management after Orthopaedic Surgery.

Official Title
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A Phase Ⅱ, Randomized, Double-blind, Placebo-controlled ， Evaluation of the Safety, Efficacy of SHR0410 Injection for Pain Management Following Orthopaedic Surgery

Conditions
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Postsurgical Pain

Intervention / Treatment
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* Drug: SHR0410 Injection
* Drug: Placebo for SHR0410 Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide a written informed consent； Subjects requiring elective general anesthesia orthopedic surgery； Male or female； Meet the body mass index standard； Conform to the ASA Physical Status Classification； Negative pregnancy test. Exclusion Criteria: Subjects with a history of myocardial infarction or unstable angina pectoris； Subjects with atrioventricular block or cardiac insufficiency； Subjects with a history of malignancy ； Subjects with a history of stroke； Subjects with a history of mental illness； Subjects with a history of difficult airway； Random blood glucose ≥11.1mmol/L； Subjects with poor blood pressure control； Abnormal values in liver or renal function； Subject with a history of substance abuse and drug abuse； Allergic to drugs that may be used during the study； Use other drugs that affect the analgesic effect before randomization, and the time from the last use to randomization is shorter than 5 half-lives； Participated in clinical trials of other drugs (received experimental drugs)； Other circumstances that the investigator judged inappropriate for participation in this clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: SHR0410 Injection compared with placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR0410 Injection High dose<br> | Drug: SHR0410 Injection<br>* SHR0410 Injection<br>|
| Experimental: SHR0410 Injection Low dose<br> | Drug: SHR0410 Injection<br>* SHR0410 Injection<br>|
| Placebo Comparator: Placebo for SHR0410 Injection<br> | Drug: Placebo for SHR0410 Injection<br>* SHR0410 Injection blank preparation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Usage of Morphine, Post Surgery | Change in the amount of morphine use (in milligrams) by subjects in each treatment group for a 48 hour period post IP administration | 0 hour to 48 hours after IP administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Usage of Morphine, Post Surgery at other intervals | Change in the amount of morphine use (in milligrams) by subjects in each treatment group for 0-24 hours after IP administration.Change in the amount of morphine use (in milligrams) by subjects in each treatment group for 4-48 hours after IP administration. | 0 hour to 24 hours after IP administration ；24 hours to 48 hours after IP administration | 
| the Sum of Pain Intensity Differences in Pain Score Over 6、12、24、48 、12-24、24-48 Hours under static condition | Pain intensity will be evaluated using an 11-point (0-10) Numeric Rating Scale (NRS), with higher numbers indicating a higher pain intensity, administered over 48 hours. Time weighted average change from baseline is calculated using the following: time weighted sum of pain intensity differences (SPID) divided by a constant (48 hours) to yield values on the 0-10 NRS. | 48-hours | 
| the Sum of Pain Intensity Differences in Pain Score Over 6、12、24、48 、12-24、24-48 Hours under moving condition | Pain intensity will be evaluated using an 11-point (0-10) Numeric Rating Scale (NRS), with higher numbers indicating a higher pain intensity, administered over 48 hours. Time weighted average change from baseline is calculated using the following: time weighted sum of pain intensity differences (SPID) divided by a constant (48 hours) to yield values on the 0-10 NRS. | 48-hours | 
| Time to First Dose of Rescue Analgesia | Time to first rescue was calculated as the elapsed time from administration of Dose 1 to the administration of the first dose of rescue analgesia. | 0 hour to 48 hours after IP administration | 
| Frequency of Doses of Rescue Analgesia Utilized Per Subject， total consumption of morphine Rescue Analgesia Utilized Per Subject | Rescue analgesia was available to subjects with inadequately controlled pain upon request. | 0 hour to 24 hours after IP administration ；24 hours to 48 hours after IP administration ；0 hour to 48 hours after IP administration | 
| Total press times of PCA pump and effective press times of PCA pump | Read and record the press times and effective press times from PCA | 0 hour to 24 hours after IP administration ；24 hours to 48 hours after IP administration ；0 hour to 48 hours after IP administration | 
| Proportion of subjects who did not receive Rescue Analgesia | Proportion of rescue was calculated as the elapsed time from administration of Dose 1 to the administration of the first dose of rescue analgesia. | 0 hour to 24 hours after IP administration ；24 hours to 48 hours after IP administration ；0 hour to 48 hours after IP administration | 
| Participant ' satisfaction score for analgesia treatment | Participants recalled the postoperative analgesia effect and rated their satisfaction on a scale of 0 to 10, with 0 representing dissatisfied and 10 representing very satisfied. | 48-hours | 
| Investigator satisfaction score for analgesia treatment | Postoperative analgesia was evaluated by investigators. The scale ranges from 0 to 10, with 0 being dissatisfied and 10 being very satisfied | 48-hours |