Phase 2 Herniorrhaphy Study for Opioid Elimination

Study Overview
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Brief Summary
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This is a Phase 2, open-label study in subjects undergoing unilateral open inguinal herniorrhaphy.

Official Title
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A Phase 2, Open-Label Study of HTX 011 in a Multimodal Analgesic Regimen for Decreased Opioid Use Following Unilateral Open Inguinal Herniorrhaphy

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: HTX-011
* Device: Luer lock applicator
* Device: Vial access device
* Drug: Ibuprofen
* Drug: Acetaminophen
* Drug: Ketorolac


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is scheduled to undergo a unilateral open inguinal herniorrhaphy with mesh under general anesthesia. Has an American Society of Anesthesiologists Physical Status of I, II, or III. Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant during the study, sterile; or using acceptable contraceptives. Exclusion Criteria: Had any prior inguinal hernia repair except as a child (less than 6 years of age). Has a planned concurrent surgical procedure (eg, bilateral herniorrhaphy). Has a pre-existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain. Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications. Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months. Has taken any NSAIDs within least 10 days prior to the scheduled surgery. Has taken long-acting opioids within 3 days prior to the scheduled surgery. Has taken any opioids within 24 hours prior to the scheduled surgery. Has been administered bupivacaine within 5 days prior to the scheduled surgery. Has been administered any local anesthetic within 72 hours prior to the scheduled surgery. Has initiated treatment with study medications within 1 month prior to study drug administration that can impact pain control. Has been administered systemic steroids within 5 half-lives or 10 days prior to administration of study drug. Has a medical condition such that, in the opinion of the Investigator, participating in the study would pose a health risk to the subject or confound the postoperative assessments. As per subject history and/or medical records, has active infection or is currently undergoing treatment for Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV). Has uncontrolled anxiety, psychiatric, or neurological disorder. Had a malignancy in the last year, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix. Has a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse. Note: Subjects with a positive drug screen who are taking an allowed, prescribed medication that is known to result in a positive drug test (eg, amphetamine and dextroamphetamine for attention-deficit/hyperactivity disorder, benzodiazepine for anxiety disorder) may be eligible for participation in the study at the discretion of the Sponsor. Subjects taking any marijuana (medical or recreational) are not allowed to participate in the study. Previously participated in an HTX-011 study. Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half-lives. Has undergone 3 or more surgeries within 12 months. Has a body mass index (BMI) >39 kg/m2.

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: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: HTX-011 + MMA Regimen<br>HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen. | Drug: HTX-011<br>* HTX-011 (bupivacaine/meloxicam), 300 mg/ 9 mg via instillation.<br>Device: Luer lock applicator<br>* Applicator for instillation.<br>Device: Vial access device<br>* Device for withdrawal of drug product.<br>Drug: Ibuprofen<br>* Ibuprofen, 600 mg.<br>Drug: Acetaminophen<br>* Acetaminophen, 1 g.<br>|
| Experimental: Cohort 2: HTX-011 + MMA Regimen + Ketorolac<br>HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen and IV ketorolac. | Drug: HTX-011<br>* HTX-011 (bupivacaine/meloxicam), 300 mg/ 9 mg via instillation.<br>Device: Luer lock applicator<br>* Applicator for instillation.<br>Device: Vial access device<br>* Device for withdrawal of drug product.<br>Drug: Ibuprofen<br>* Ibuprofen, 600 mg.<br>Drug: Acetaminophen<br>* Acetaminophen, 1 g.<br>Drug: Ketorolac<br>* Intraoperative IV ketorolac.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Receiving no Opioid Rescue |  | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [IV MME]) |  | 72 hours | 
| Percentge of Subjects Receiving no Opioid Rescue |  | 0-24 hours, 24-48 hours, 24-72 hours, 48-72 hours | 
| Percentge of Subjects Receiving no Opioid Rescue |  | Day 28 | 
| Percentge of Subjects in Severe Pain With Numeric Rating Scale (NRS-R; Windowed Worst Observation Carried Forward) of Pain Intensity Scores >7 on a Scale of 0-10 at Any Point. NRS-R for Pain Where 0 Equals no Pain and 10 Equals Worst Pain Imaginable. |  | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inguinal hernia, hernia, hernia surgery, postoperative pain, herniorrhaphy