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

Postoperative Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03262688
• Other study ID #: INN-CB-020
• Status: Recruiting
• Phase: Phase 3
• Start date: June 16, 2017
• Est. completion date: January 31, 2024

Study information

• Verified date: July 2021
• Source: Innocoll
• Contact: Nina Head of Clinical Operations
• Phone: 484-406-5214
• Email: rsmall[@]innocoll.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 159
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 16 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hernia
• Hernia, Inguinal
• Inguinal Hernia
• Postoperative Pain

Intervention

Drug:
• Bupivacaine HCl collagen-matrix implant
Placement of the bupivacaine collagen-matrix in the surgical site
• Bupivacaine HCl infiltration
Infiltration of the surgical site

Locations

Country	Name	City	State
United States	Cornerstone Research Institute	Altamonte Springs	Florida
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	El Paso Children's Hospital	El Paso	Texas
United States	Memorial Hermann Memorial City Medical Center	Houston	Texas
United States	The Woman's Hospital of Texas	Houston	Texas
United States	Alliance Research Centers	Laguna Hills	California
United States	Elion & Volhard Pharmaceutical Research (E&V PR)	Miami	Florida
United States	Medical Research Center	Miami	Florida
United States	Children's Hospital of Pittsburgh of UPMC (CHP-UPMC)	Pittsburgh	Pennsylvania
United States	Plano Surgical Hospital	Plano	Texas
United States	Jean Brown Research	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Innocoll	Premier Research Group plc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Possibly related to bupivacaine toxicity	30 days
Primary	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
Primary	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
Primary	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
Primary	Body temperature	Signs/symptoms of bupivacaine toxicity	Through Day 30
Primary	12-lead ECG	Screening only	1 day at screening
Primary	3-lead ECG	Signs/symptoms of bupivacaine toxicity	Starting at Time 0 and continuing for at least 3 hours
Primary	Oxygen saturation levels	Pulse oximetry	Starting at Time 0 and continuing for at least 3 hours
Primary	Clinical laboratory testing	Collection of blood and urine samples	1 day at screening
Primary	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
Primary	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
Primary	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	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.
Secondary	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
Secondary	AUC0-8	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
Secondary	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
Secondary	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
Secondary	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