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
Overview
- Phase
- Phase 3
- Intervention
- Bupivacaine HCl collagen-matrix implant
- Conditions
- Inguinal Hernia
- Sponsor
- Innocoll
- Enrollment
- 159
- Locations
- 11
- Primary Endpoint
- Adverse events
- Last Updated
- 4 years ago
Overview
Brief 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).
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
INL-001
Bupivacaine HCl collagen-matrix implant
Intervention: Bupivacaine HCl collagen-matrix implant
Infiltration
Bupivacaine HCl infiltration
Intervention: Bupivacaine HCl infiltration
Outcomes
Primary Outcomes
Adverse events
Time Frame: 30 days
Possibly related to bupivacaine toxicity
Blood pressure (systolic/diastolic)
Time Frame: Starting at Time 0 and continuing for 3 hours and then 5, 8, 12, 24, 36, and 48 hours after Time 0
Signs/symptoms of bupivacaine toxicity
Heart rate
Time Frame: Continuously from Time 0 through 3 hours, and then 5, 8, 12, 24, 36, and 48 hours after Time 0
Signs/symptoms of bupivacaine toxicity
Respiratory rate
Time Frame: Continuously from Time 0 through 3 hours, and then 5, 8, 12, 24, 36, and 48 hours after Time 0
Signs/symptoms of bupivacaine toxicity
Body temperature
Time Frame: Through Day 30
Signs/symptoms of bupivacaine toxicity
12-lead ECG
Time Frame: 1 day at screening
Screening only
3-lead ECG
Time Frame: Starting at Time 0 and continuing for at least 3 hours
Signs/symptoms of bupivacaine toxicity
Oxygen saturation levels
Time Frame: Starting at Time 0 and continuing for at least 3 hours
Pulse oximetry
Clinical laboratory testing
Time Frame: 1 day at screening
Collection of blood and urine samples
Wound healing assessments
Time Frame: Assessment on Day 1 through Day 3; follow-up evaluations on Days 7, 15 and 30
Inspection of surgical wound site for signs of wound infection and dehiscence.
Nausea
Time Frame: 1, 2, 4, 6, 12, 24, 36, and 48 hours after Time 0
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
Sedation
Time Frame: 1, 2, 4, 6, 12, 24, 36, and 48 hours after Time 0
Sedation scores: awake and alert = 0, quietly awake = 1, asleep but easily roused = 2, and deep sleep = 3.
Secondary Outcomes
- Cmax(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(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-∞(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(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(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(1, 2, 4, 6, 12, 24, 36, and 48 hours after Time 0)