Safety, Tolerability, PK, and Analgesic Effect of INL-001 in Children Following Open Inguinal Hernia Repair

A Multicenter, Randomized, Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Analgesic Effect of the INL-001 Bupivacaine Hydrochloride (HCl) Collagen-Matrix Implant in Children 2 to <17 Years of Age Following Open Inguinal Hernia Repair

A multicenter, single-dose study in children 12 to <17 years of age, 6 to <12 years of age, and 2 to <6 years of age who are scheduled for elective open inguinal hernia repair. Enrollment in this study will start with the oldest age group (12 to <17 years) and will continue in a stepwise fashion until appropriate doses are established for all 3 pediatric age groups (12 to <17 years, 6 to <12 years, 2 to <6 years).

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain; Inguinal Hernia
• Intervention / Treatment: Drug: Bupivacaine HCl collagen-matrix implant; Drug: Bupivacaine HCl infiltration

Detailed Description

This is a multicenter, single-dose study in children 12 to <17 years of age, 6 to <12 years of age, and 2 to <6 years of age who are scheduled for elective open inguinal hernia repair. Within 21 days of surgery, eligible subjects will be screened and have routine clinical laboratory testing and an electrocardiogram performed. Subjects will then undergo an open inguinal hernia repair under general anesthesia according to the investigator's standard surgical practice on day 1. Enrollment in this study will start with the oldest age group (12 to <17 years) and will continue in a stepwise fashion until appropriate doses are established for all 3 pediatric age groups. Within each age group, the study will be conducted in 3 parts.

Children in each age group who are randomized to INL-001 will receive approximately less than or equal to 2.5 mg/kg of INL-001. Study drug will be administered prior to wound closure. The INL-001 implant will be cut before placement into the surgical site using sterile technique. Children randomized to 0.25% bupivacaine HCl injection will receive 2.5 mg/kg according to standard practice.

After completion of the surgical procedure, all subjects will remain in the post-anesthesia care unit for at least 3 hours and will be continuously monitored for safety. At the discretion of the investigator, subjects may receive rescue medication (opioid or nonopioid) upon request for the management of breakthrough pain and may receive an antiemetic for the management of nausea or vomiting. After the initial 3-hour period, subjects who are deemed stable may be discharged to the hospital ward. Subjects will remain housed in the hospital ward for at least 48 hours. Blood samples will be collected for pharmacokinetic analysis from a subset of 8 children in each age group after INL-001 is implanted.

• Study Type: Interventional
• Enrollment (Anticipated): 159
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nina Head of Clinical Operations; Phone Number: 484-406-5214; Email: rsmall@innocoll.com
• Study Contact Backup: Name: Nina Head of Clinical Research, MD; Phone Number: 484-406-5205; Email: nskuban@innocoll.com

Study Locations

• United States
  • California
    • Laguna Hills, California, United States, 92653
      • Recruiting
      • Alliance Research Centers
      • Contact: Tracy Bessette; Phone Number: 949-680-3490; Email: tbessette@researchalliance.com
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Recruiting
      • Cornerstone Research Institute
      • Contact: Derrica Robinson; Phone Number: 407-729-1236; Email: drobinson@cornerstonestudy.com
    • Miami, Florida, United States, 33144
      • Withdrawn
      • Medical Research Center
    • Miami, Florida, United States, 33165
      • Withdrawn
      • Elion & Volhard Pharmaceutical Research (E&V PR)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • Children's Hospital of Pittsburgh of UPMC (CHP-UPMC)
      • Contact: Denise McCarthy; Phone Number: 412-692-5585; Email: mccarthydj@anes.upmc.edu
  • Texas
    • Corpus Christi, Texas, United States, 78411
      • Recruiting
      • Driscoll Children's Hospital
      • Contact: Debhanhi Gaylan; Phone Number: 540-314-1838; Email: debhanhi@researchhd.com
    • El Paso, Texas, United States, 79905
      • Recruiting
      • El Paso Children's Hospital
      • Contact: Isaac Martinez; Phone Number: 915-244-0751; Email: isaac@researchhd.com
    • Houston, Texas, United States, 77024
      • Recruiting
      • Memorial Hermann Memorial City Medical Center
      • Contact: Jayme Carr; Phone Number: 832-524-7177; Email: jayme@researchHD.com
    • Houston, Texas, United States, 77054
      • Withdrawn
      • The Woman's Hospital of Texas
    • Plano, Texas, United States, 75093
      • Recruiting
      • Plano Surgical Hospital
      • Contact: Laura Kade; Phone Number: 410-614-5775; Email: laura@researchhd.com
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Active, not recruiting
      • Jean Brown Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Be a male or female 2 to <17 years of age.
• Be eligible for an elective open inguinal hernia repair that will be performed according to standard surgical technique under general anesthesia.
• Be premenarche or have a serum confirmed negative pregnancy test at screening and a negative urine pregnancy test before surgery on day 1, if an adolescent female of childbearing potential.
• Be willing and able to cooperate with all the requirements of the study.
• Be able to speak and understand English or Spanish.
• Have a legally authorized representative (eg, parent, guardian) who is able to read, speak, and understand English or Spanish and who will voluntarily sign and date a parental permission/informed consent form that is approved by the Institutional Review Board/Independent Ethics Committee/Human Research Ethics Committee (IRB/IEC/HREC).
• Be willing to sign an assent (if appropriate dependent upon the child's age, understanding, and IRB requirements), before the conduct of any study procedure.

Exclusion Criteria:

• Has a known hypersensitivity to amide local anesthetics, bovine products, or to inactive ingredients of the study drugs.
• Requires any additional surgical procedures, either related or unrelated to the scheduled surgery (ie, open inguinal hernia surgery), during the same hospitalization.
• Requires epidural or spinal blockade perioperatively.
• Is required to receive neuraxial (spinal or epidural) opioid analgesics during the study.
• Has undergone major surgery within 3 months of the scheduled surgery or plans to undergo another surgical procedure within the 30-day postoperative period.
• Has known or suspected history of drug abuse or misuse or evidence of tolerance or physical dependency on opioid analgesics or sedative-hypnotic medications.
• Has participated in a clinical trial (investigational or marketed product) within 30 days before surgery.
• Has any clinically significant medical history or condition (eg, unstable cardiac, neurological, immunological, renal, hepatic, or hematological disease or any other condition) that in the opinion of the investigator, substantially increases the risk associated with the subject's participation in the protocol or compromises the scientific objectives of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: INL-001; Bupivacaine HCl collagen-matrix implant	Drug: Bupivacaine HCl collagen-matrix implant; Placement of the bupivacaine collagen-matrix in the surgical site; Other Names: Xaracoll
ACTIVE_COMPARATOR: Infiltration; Bupivacaine HCl infiltration	Drug: Bupivacaine HCl infiltration; Infiltration of the surgical site; Other Names: Marcaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Possibly related to bupivacaine toxicity	30 days
Blood pressure (systolic/diastolic)	Signs/symptoms of bupivacaine toxicity	Starting at Time 0 and continuing for 3 hours and then 5, 8, 12, 24, 36, and 48 hours after Time 0
Heart rate	Signs/symptoms of bupivacaine toxicity	Continuously from Time 0 through 3 hours, and then 5, 8, 12, 24, 36, and 48 hours after Time 0
Respiratory rate	Signs/symptoms of bupivacaine toxicity	Continuously from Time 0 through 3 hours, and then 5, 8, 12, 24, 36, and 48 hours after Time 0
Body temperature	Signs/symptoms of bupivacaine toxicity	Through Day 30
12-lead ECG	Screening only	1 day at screening
3-lead ECG	Signs/symptoms of bupivacaine toxicity	Starting at Time 0 and continuing for at least 3 hours
Oxygen saturation levels	Pulse oximetry	Starting at Time 0 and continuing for at least 3 hours
Clinical laboratory testing	Collection of blood and urine samples	1 day at screening
Wound healing assessments	Inspection of surgical wound site for signs of wound infection and dehiscence.	Assessment on Day 1 through Day 3; follow-up evaluations on Days 7, 15 and 30
Nausea	Measured using a categorical scoring system (none = 0, mild = 1, moderate = 2, and severe = 3). Nausea scores will also be recorded immediately before the use of rescue antiemetics	1, 2, 4, 6, 12, 24, 36, and 48 hours after Time 0
Sedation	Sedation scores: awake and alert = 0, quietly awake = 1, asleep but easily roused = 2, and deep sleep = 3.	1, 2, 4, 6, 12, 24, 36, and 48 hours after Time 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed plasma concentration	0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hour time points after Time 0.
AUC0-last	Area under the plasma concentration time curve from Time zero to last quantifiable plasma concentration	0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hour time points after Time 0
AUC0-∞	Area under the plasma concentration time curve from Time zero to extrapolated through infinity	0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hour time points after Time 0
Tmax	Time to maximum obserbved plasma concentration	0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hour time points after Time 0
t1/2	Apparent first-order terminal elimination half-life	0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hour time points after Time 0
Pain intensity	Assessed using an 11-point NRS (for children 12 to <17 years of age), a FACES pain severity scale (children 4 through <12 years of age), or FLACC (children 2 and 3 years of age) immediately before the child receives any parenteral or oral rescue medication for breakthrough pain	1, 2, 4, 6, 12, 24, 36, and 48 hours after Time 0

Collaborators and Investigators

• Sponsor: Innocoll
• Collaborators: Premier Research Group plc
• Investigators: Study Director: Gwendolyn Niebler, DO, Innocoll

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 16, 2017
• Primary Completion (ANTICIPATED): January 31, 2024
• Study Completion (ANTICIPATED): January 31, 2024

Study Registration Dates

• First Submitted: August 21, 2017
• First Submitted That Met QC Criteria: August 24, 2017
• First Posted (ACTUAL): August 25, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 23, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Children; Pediatric; Inguinal hernia; Bupivacaine; Collagen; INL-001
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Hernia, Abdominal; Hernia; Hernia, Inguinal; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: INN-CB-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No