Pediatric Postoperative Analgesia Herniorrhaphy Study

Overview

This is a Phase 2, double-blind study in pediatric subjects undergoing inguinal herniorrhaphy.

Full Title of Study: “A Phase 2, 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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 2021

Detailed Description

Up to 360 subjects will be randomized into one of three age cohorts: Cohort 1 (approximately 128 adolescents ≥12 to <17 years), Cohort 2 (approximately 128 children ≥6 to <12 years), and Cohort 3 (approximately 104 children ≥3 to <6 years). Cohorts 1 and 2 will be conducted in two parts: Part A will be dose-ranging and Part B will further evaluate the HTX-011 dose identified in Part A. All subjects enrolled in the study will be randomized to receive either HTX-011 via instillation into the surgical site or bupivacaine HCl 0.25% without epinephrine via injection into the surgical site. The study will enroll subjects in a staggered sequence (from oldest to youngest) of the 3 age cohorts. An Interim Review Committee will monitor the safety of each HTX-011 dose group. All subjects will be screened within 28 days prior to surgery. On the day of surgery, eligible subjects will undergo open unilateral herniorrhaphy under general anesthesia and will receive assigned study drug near the completion of the surgery. Subjects will remain in the hospital/research facility for 72 hours after the start of study drug administration to undergo postoperative assessments. After 72 hours, subjects can be discharged and will undergo follow-up assessments on Days 5, 7 and 28.

Interventions

  • Drug: HTX-011
    • Single-dose instillation of approximately 0.17 mL/kg (total dose does not exceed 10.5 mL) of HTX-011.
  • Device: Luer lock applicator
    • Applicator for instillation.
  • Drug: Bupivacaine HCl
    • Bupivacaine HCl 0.25% (without epinephrine) 0.5 to 1.0 mL/kg (total dose not to exceed 75 mg).
  • Drug: HTX-011
    • Dose to be determined from Cohort 1.
  • Drug: HTX-011
    • Dose to be determined from Cohorts 1 and 2.
  • Drug: HTX-011
    • Dose to be determined from Cohort 1 Part A.

Arms, Groups and Cohorts

  • Experimental: Cohort 1 Part A: HTX-011
    • Adolescents ≥12 to <17 years of age. A single dose of HTX-011 via instillation into the surgical site.
  • Active Comparator: Cohort 1 Part A: bupivacaine HCl
    • Adolescents ≥12 to <17 years of age. A single dose of bupivacaine HCl 0.25% (without epinephrine) via injection into the surgical site.
  • Experimental: Cohort 1 Part B: HTX-011
    • Adolescents ≥12 to <17 years of age. Dose to be determined from Cohort 1 Part A.
  • Active Comparator: Cohort 1 Part B: bupivacaine HCl
    • Adolescents ≥12 to <17 years of age. A single dose of bupivacaine HCl 0.25% (without epinephrine) via injection into the surgical site
  • Experimental: Cohort 2 Part A: HTX-011
    • Children ≥6 to <12 years of age. Dose to be determined from Cohort 1.
  • Active Comparator: Cohort 2 Part A: bupivacaine HCl
    • Children ≥6 to <12 years of age. A single dose of bupivacaine HCl 0.25% (without epinephrine) via injection into the surgical site
  • Experimental: Cohort 2 Part B: HTX-011
    • Children ≥6 to <12 years of age. Dose to be determined from Cohort 1.
  • Active Comparator: Cohort 2 Part B: bupivacaine HCl
    • Children ≥6 to <12 years of age. A single dose of bupivacaine HCl 0.25% (without epinephrine) via injection into the surgical site
  • Experimental: Cohort 3: HTX-011
    • Children ≥3 to <6 years of age. Dose to be determined from Cohorts 1 and 2.
  • Active Comparator: Cohort 3: bupivacaine HCl
    • Children ≥3 to <6 years of age. A single dose of bupivacaine HCl 0.25% (without epinephrine) via injection into the surgical site

Clinical Trial Outcome Measures

Primary Measures

  • Area under the plasma concentration-time curve (AUC) from Time 0 extrapolated to infinity (AUCinf)
    • Time Frame: 72 hours
  • Maximum observed plasma concentration (Cmax)
    • Time Frame: 72 hours
  • Time to maximum plasma concentration (Tmax)
    • Time Frame: 72 hours

Secondary Measures

  • 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)
    • Time Frame: 72 hours
  • Children ≥6 to <12 years of age (Cohort 2): AUC of the Faces-Pain-Scale (FPS)-Revised pain intensity scores
    • Time Frame: 72 hours
  • Children ≥3 to <6 years of age (Cohort 3): AUC of the Faces, Legs, Activity, Cry, Consolability (FLACC) scale pain intensity scores
    • Time Frame: 72 hours
  • Total postoperative opioid consumption (in IV morphine milligram equivalents)
    • Time Frame: 72 hours
  • Proportion of subjects who are opioid-free
    • Time Frame: 72 hours
  • AUC of the Numeric Rating Scale pain intensity scores at rest (NRS-R)
    • Time Frame: 72 hours

Participating in This Clinical Trial

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:

  • 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 had a prior ipsilateral inguinal herniorrhaphy. – 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 underlying history of chronic opioid use or opioid abuse. – 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) >35 kg/m2.

Gender Eligibility: All

Minimum Age: 3 Years

Maximum Age: 16 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Heron Therapeutics
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Erol Onel, (858) 251-4420, HTX011-ct@herontx.com

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.