Phase Ⅱ Study of Adductor Canal Block With HR18034 for Postsurgical Pain Management

Study Overview
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Brief Summary
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Phase Ⅱ, randomized, double-blind, comparator-controlled study to evaluate the efficacy, safety and pharmacokinetics of single injection adductor canal block with HR18034 for postoperative pain management compared with ropivacaine.

Official Title
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A Phase Ⅱ Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Single Injection Adductor Canal Block With HR18034 for Postoperative Pain Management

Conditions
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Total Knee Arthroplasty

Intervention / Treatment
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* Drug: HR18034;Ropivacaine Hydrochloride Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide a written informed consent Scheduled to undergo primary unilateral total knee arthroplasty under general anesthesia. Male or female，aged 18-75 years inclusive Body mass index (BMI) 18-28 kg/m2 inclusive American Society of Anesthesiologists (ASA) Physical Status Classification Ⅰ Ⅱ Exclusion Criteria: Subjects with deformity of the involving operative limb, or other neuropathy Subjects with a history of new myocardial infarction or unstable angina within 6 months prior to randomization; Subjects with a history of ischemic stroke or transient ischemic attack (TIA) Subjects with a history of mental system diseases and cognitive dysfunction Combination of other pain conditions that may affect postoperative pain assessment Persistent or recurrent nausea and/or vomiting due to other etiologies, including, but not limited to gastric outlet obstruction, hypercalcemia, or active peptic ulcer Subjects with a history of deep vein thrombosis-related disease Clinically significant abnormal clinical laboratory test value Allergic to a drug ingredient or component Use of any of medications, which affect drug metabolism or analgesia evaluation, within 5 half-lives or as specified prior to the study surgical procedure History of alcohol abuse or prescription and/or illicit drug abuse Subjects with special diets (including tobacco, grapefruit and caffeine) Pregnant or nursing women No birth control during the specified period of time Participated in clinical trials of other drugs (received experimental drugs) The inestigators determined that other conditions were inappropriate for participation in this clinical trial

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: HR18034 compared with active comparator
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dose 1<br>Experimental: HR18034 190mg (10ml) Intervention: Drug: HR18034 Active Comparator: Ropivacaine Hydrochloride Injection Ropivacaine Hydrochloride Injection 50mg (10mL) Intervention: Drug: Ropivacaine Hydrochloride Injection | Drug: HR18034;Ropivacaine Hydrochloride Injection<br>* Drug: HR18034 Drug: Ropivacaine Hydrochloride Injection Local nerve block of Ropivacaine Hydrochloride Injection to produce anesthesia for surgery and analgesia in postoperative pain management. Other Name: Ropivacaine Hydrochloride Injection, 0.5% Injectable Solution<br>|
| Experimental: dose 2<br>Experimental: HR18034 285mg (15ml) Intervention: Drug: HR18034 Active Comparator: Ropivacaine Hydrochloride Injection Ropivacaine Hydrochloride Injection 75mg (15mL) Intervention: Drug: Ropivacaine Hydrochloride Injection | Drug: HR18034;Ropivacaine Hydrochloride Injection<br>* Drug: HR18034 Drug: Ropivacaine Hydrochloride Injection Local nerve block of Ropivacaine Hydrochloride Injection to produce anesthesia for surgery and analgesia in postoperative pain management. Other Name: Ropivacaine Hydrochloride Injection, 0.5% Injectable Solution<br>|
| Experimental: dose 3<br>Experimental:HR18034 380mg (20ml) Intervention: Drug: HR18034 Active Comparator: Ropivacaine Hydrochloride Injection Ropivacaine Hydrochloride Injection 100mg (20mL) Intervention: Drug: Ropivacaine Hydrochloride Injection | Drug: HR18034;Ropivacaine Hydrochloride Injection<br>* Drug: HR18034 Drug: Ropivacaine Hydrochloride Injection Local nerve block of Ropivacaine Hydrochloride Injection to produce anesthesia for surgery and analgesia in postoperative pain management. Other Name: Ropivacaine Hydrochloride Injection, 0.5% Injectable Solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-72 of the NRS-R pain intensity scores. | AUC of NRS pain intensity scores at rest (NRS-R) through 72 hours after the beginning of study drug administration. | 0 to 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of the NRS-R pain intensity scores. | AUC of NRS pain intensity scores at rest (NRS-R) for time periods 0-24, 0-48 hours. | 0-24, 0-48 hours | 
| AUC of the NRS-A pain intensity scores. | AUC of NRS pain intensity scores at activity (NRS-A) for time periods 0-24, 0-48, 0-72 hours. | 0-24, 0-48, 0-72 hours | 
| Pain intensity assessed using an 11-point NRS ranging. | 11-point Numercal Rating Scale ranging from a score of 0 to 10. Pain-free defined as an NRS of 0 or 1. Worst imaginable pain defined as an NRS of 10 | Baseline till 72 hours after the beginning of study drug administration | 
| Proportion of subjects who used no rescue opioid analgesic. | Proportion of subjects who used no rescue opioid analgesic through 0-24, 24-48, 48-72 and 0-72 hours after the beginning of study drug administration. | 0-24, 24-48, 48-72, 0-72 hours | 
| Total rescue analgesic consumption. | Total rescue analgesic consumption through 0-24, 24-48, 48-72 and 0-72 hours after the beginning of study drug administration. | 0-24, 24-48, 48-72, 0-72 hours | 
| Time to the first postoperative use of rescue opioid analgesics. | Time to the first postoperative use of rescue opioid analgesics 0-72 hours after the beginning of study drug administration. | 0-72hours | 
| Quadriceps muscle strength score. | Quadriceps muscle strength score at 6, 8, 12, 16, 20, 24, 36, 48 and 72 hours. | Baseline till 72 hours after the beginning of study drug administration | 
| Subjects' satisfaction rating | Subjects' satisfaction rating with postsurgical pain control at 72 hours. | 72 hours | 
| Investigators' satisfaction rating | Investigators' satisfaction rating with postsurgical pain control at 72 hours. | 72 hours |