A Trial of HR18034 in Inguinal Hernia Repair

Study Overview
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Brief Summary
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Phase I, randomized, double-blind, comparator-controlled study to assess the safety, PK, and efficacy of single postsurgical application of HR18034 compared with Naropin®

Official Title
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A Phase I Study to Evaluate the Safety, Pharmacokinetics and Efficacy of HR18034 for Pain Management After Inguinal Hernia Repair

Conditions
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Inguinal Hernia Repair

Intervention / Treatment
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* Drug: HR18034
* Drug: Naropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide a written informed consent 2、Male or female between 18 and 70 years of age 3、Scheduled to undergo a primary, inguinal hernia repair with mesh, and be able to use the anesthesia regimen 4、Meet the body mass 5、Conform to the ASA Physical Status Classification Exclusion Criteria: Clinically significant abnormal clinical laboratory test value Subjects with poor blood pressure control after medication Subjects with atrioventricular block or cardiac insufficiency Subjects with a history of myocardial infarction or unstable angina pectoris Subjects with a history of ischemic stroke or transient ischemic attack Combination of other pain conditions that may affect postoperative pain assessment Allergic to a drug ingredient or component Persistent or recurrent nausea and/or vomiting due to other etiologies, including, but not limited to gastric outlet obstruction, hypercalcemia, or active peptic ulcer History of alcohol abuse or prescription and/or illicit drug abuse within 1 years Subjects with special diets (including tobacco, grapefruit and caffeine) Positive results on the urine drug screen or alcohol breath test indicative of illicit drug or alcohol abuse. History of human immunodeficiency virus (HIV), hepatitis C, syphilis antibody，or hepatitis B. Use of any of the following medications within 14 days or as specified prior to the study surgical procedure: Have had an inguinal hernia repair in the last 3 months before the study surgical procedure or presents with bilateral or recurrent inguinal hernia, other hernia presentations, or hernias with a large scrotal component that would be difficult to reduce surgically Participated in clinical trials of other drugs (received experimental drugs) History or clinical manifestations of significant renal, hepatic, gastrointestinal, cardiovascular, metabolic, neurologic, psychiatric, or other condition. Pregnant or nursing women No birth control during the specified period of time 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: 70 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dose 1<br>HR18034（Ropivacaine Liposome for Injection） is a sustained-release liposome | Drug: HR18034<br>* HR18034（Ropivacaine Liposome for Injection） is a sustained-release liposome<br>* Other names: subjects will receive HR18034.;|
| Experimental: dose 2<br>HR18034（Ropivacaine Liposome for Injection） is a sustained-release liposome | Drug: HR18034<br>* HR18034（Ropivacaine Liposome for Injection） is a sustained-release liposome<br>* Other names: subjects will receive HR18034.;|
| Experimental: dose 3<br>HR18034（Ropivacaine Liposome for Injection） is a sustained-release liposome | Drug: HR18034<br>* HR18034（Ropivacaine Liposome for Injection） is a sustained-release liposome<br>* Other names: subjects will receive HR18034.;|
| Experimental: dose 4<br>HR18034（Ropivacaine Liposome for Injection） is a sustained-release liposome | Drug: HR18034<br>* HR18034（Ropivacaine Liposome for Injection） is a sustained-release liposome<br>* Other names: subjects will receive HR18034.;|
| Active Comparator: Naropin<br>Naronpin injection contains ropivacaine HCl. Strength: 150mg/ 30mL (5 mg/mL) Size: 30mL fill, in a 30mL single dose vial | Drug: Naropin<br>* Local infiltration of Naropin to produce anesthesia for surgery and analgesia in postoperative pain management. Naropin 150mg [0.5%, 5mg/mL] x 30mL<br>* Other names: Naropin, 0.5% Injectable Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of SAEs and treatment-related severe AEs | Safety and tolerability: | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity assessed using an 11-point NPRS ranging | 11-point Numercal Pain Rating Scale ranging from a score of 0 to 10. Pain-free defined as an NPRS of 0 or 1. Worst imaginable pain defined as an NPRS of 10 | Baseline till 168 hours post IP administration | 
| AUC of NPRS | AUC of NPRS for time periods 0-12, 0-24, 0-36, 0-48, 0-72, and 0-96 hours | For time periods 0-12, 0-24, 0-36, 0-48, 0-72, and 0-96 hours | 
| Patient Global Assessment of the method of pain control | Patient Global Assessment ranging from a score of 0 to 10. Satisfaction defined as a scale of 10, dissatisfaction defined as a scale of 0. | 24 hours post IP administration till 168 hours post IP administration | 
| Proportion of pain-free subjects at scheduled timepoints. | Pain-free defined as an NPRS of 0 or 1 | Baseline till 168 hours post IP administration | 
| Proportion of subjects who used no rescue opioid analgesic | Proportion of subjects who used no rescue opioid analgesic | Baseline till 168 hours post IP administration | 
| Average daily rescue analgesic consumption | Average daily rescue analgesic consumption through 24, 48, 72 and 96 hours | Baseline till 168 hours post IP administration | 
| Time to the first postoperative use of rescue opioid analgesics | Time to the first postoperative use of rescue opioid analgesics | Baseline till 168 hours post IP administration | 
| PK Cmax | Maximum blood concentration (Cmax) | Baseline till 168 hours post IP administration | 
| Wound assessment by Wound healing and status score | The surgical site will be examined by the investigator using Wound healing and status score. Wound healing and status score ranging from a score of 0 to 4，Good defined as a scale of 0. Worst defined as a scale of 4. | Day 1 through Day 14 | 
| PK AUC | Area under the blood concentration-time curve (AUC) | Baseline till 168 hours post IP administration |