Pediatric Postoperative Analgesia Herniorrhaphy Study

Study Overview
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Brief Summary
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This is a Phase 2 study in pediatric subjects undergoing inguinal herniorrhaphy.

Official Title
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A Phase 2, 2-Part, Open-Label, Dose-Finding and Double-Blind Study to Assess the Pharmacokinetics, Pharmacodynamics, and Safety of HTX-011 for Postoperative Analgesia in Adolescents and Children (≥3 to <17 Years of Age) Undergoing Unilateral Open Inguinal Herniorrhaphy

Conditions
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Analgesia

Intervention / Treatment
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* Drug: HTX-011
* Drug: Bupivacaine HCl
* Drug: HTX-011
* Drug: HTX-011
* Drug: HTX-011
* Device: Luer Lock Applicator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is scheduled to undergo a unilateral open inguinal herniorrhaphy with or without 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: 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. Has a planned concurrent surgical procedure (eg, bilateral herniorrhaphy). Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications. Has taken meloxicam within least 10 days 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 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 a body mass index (BMI) >35 kg/m2. In addition to the preceding exclusion criteria 1 through 14, subjects to be enrolled in Cohort 1 Part B, Cohort 2 Part B, or Cohort 3 who meet any of the following criteria prior to randomization will be excluded from the study: Has had a prior ipsilateral inguinal 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 known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months. Has taken long-acting opioids within 3 days prior to the scheduled surgery. Has taken any opioids within 48 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 undergone 3 or more surgeries within 12 months.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 16 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: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Part A: HTX-011<br>Adolescents ≥12 to <17 years of age. A single dose of HTX-011 via instillation into the surgical site. | Drug: HTX-011<br>* Single-dose instillation of approximately 0.17 mL/kg (total dose does not exceed 10.5 mL) of HTX-011.<br>Device: Luer Lock Applicator<br>* Applicator for instillation.<br>|
| Active Comparator: Cohort 1 Part A: bupivacaine HCl<br>Adolescents ≥12 to <17 years of age. A single dose of bupivacaine HCl 0.25% (without epinephrine) via injection into the surgical site. | Drug: Bupivacaine HCl<br>* Bupivacaine HCl 0.25% (without epinephrine) (total dose not to exceed 75 mg).<br>|
| Experimental: Cohort 1 Part B: HTX-011<br>Adolescents ≥12 to <17 years of age. Dose to be determined from Cohort 1 Part A. | Drug: HTX-011<br>* Dose to be determined from Cohort 1 Part A.<br>Device: Luer Lock Applicator<br>* Applicator for instillation.<br>|
| Active Comparator: Cohort 1 Part B: bupivacaine HCl<br>Adolescents ≥12 to <17 years of age. A single dose of bupivacaine HCl 0.25% (without epinephrine) via injection into the surgical site | Drug: Bupivacaine HCl<br>* Bupivacaine HCl 0.25% (without epinephrine) (total dose not to exceed 75 mg).<br>|
| Experimental: Cohort 2 Part A: HTX-011<br>Children ≥6 to <12 years of age. Dose to be determined from Cohort 1. | Drug: HTX-011<br>* Dose to be determined from Cohort 1.<br>Device: Luer Lock Applicator<br>* Applicator for instillation.<br>|
| Active Comparator: Cohort 2 Part A: bupivacaine HCl<br>Children ≥6 to <12 years of age. A single dose of bupivacaine HCl 0.25% (without epinephrine) via injection into the surgical site | Drug: Bupivacaine HCl<br>* Bupivacaine HCl 0.25% (without epinephrine) (total dose not to exceed 75 mg).<br>|
| Experimental: Cohort 2 Part B: HTX-011<br>Children ≥6 to <12 years of age. Dose to be determined from Cohort 1. | Drug: HTX-011<br>* Dose to be determined from Cohort 1.<br>Device: Luer Lock Applicator<br>* Applicator for instillation.<br>|
| Active Comparator: Cohort 2 Part B: bupivacaine HCl<br>Children ≥6 to <12 years of age. A single dose of bupivacaine HCl 0.25% (without epinephrine) via injection into the surgical site | Drug: Bupivacaine HCl<br>* Bupivacaine HCl 0.25% (without epinephrine) (total dose not to exceed 75 mg).<br>|
| Experimental: Cohort 3: HTX-011<br>Children ≥3 to <6 years of age. Dose to be determined from Cohorts 1 and 2. | Drug: HTX-011<br>* Dose to be determined from Cohorts 1 and 2.<br>Device: Luer Lock Applicator<br>* Applicator for instillation.<br>|
| Active Comparator: Cohort 3: bupivacaine HCl<br>Children ≥3 to <6 years of age. A single dose of bupivacaine HCl 0.25% (without epinephrine) via injection into the surgical site | Drug: Bupivacaine HCl<br>* Bupivacaine HCl 0.25% (without epinephrine) (total dose not to exceed 75 mg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve (AUC) from Time 0 extrapolated to infinity (AUCinf) |  | 72 hours | 
| Maximum concentration (Cmax) |  | 72 hours | 
| Time of occurrence of maximum concentration (Tmax) |  | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adolescents ≥12 to <17 years of age (Cohort 1): area under the curve (AUC) of the Numeric Rating Scale of pain intensity scores with activity (NRS-A) |  | 72 hours | 
| Children ≥6 to <12 years of age (Cohort 2): AUC of the Faces-Pain-Scale (FPS)-Revised pain intensity scores |  | 72 hours | 
| Children ≥3 to <6 years of age (Cohort 3): AUC of the Faces, Legs, Activity, Cry, Consolability (FLACC) scale pain intensity scores |  | 72 hours | 
| Total postoperative opioid consumption (in IV morphine milligram equivalents) |  | 72 hours | 
| Proportion of subjects who are opioid-free |  | 72 hours | 
| AUC of the Numeric Rating Scale pain intensity scores at rest (NRS-R) |  | 72 hours | 
| Proportion of subjects who do not receive an opioid prescription at discharge. |  | 72 hours | 

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