Overview
This Phase 1, multicenter, open-label, randomized, bupivacaine-controlled study is designed to evaluate the pharmacokinetics (PK) and safety of EXPAREL vs. bupivacaine HCl for postsurgical analgesia in pediatric subjects aged 0 to less than 6 years of age undergoing cardiac surgery, utilizing local infiltration analgesia (LIA).
Description
This study will be conducted in 3 Parts (Part 1, Part 2, and Part 3) and a total of approximately 48 male and female subjects will be enrolled.
Part 1 will enroll approximately 16 subjects, aged 2 to less than 6 years to obtain information on PK and safety. Subjects will be randomized 1:1 (8 EXPAREL subjects and 8 bupivacaine HCl subjects) to receive either a single dose of EXPAREL 4 mg/kg (not to exceed a maximum total dose of 266 mg) or 0.25% bupivacaine HCl 2 mg/kg (not to exceed a maximum total dose of 175 mg) using LIA. The overall PK and safety profiles from Part 1 will be completed, analyzed, and reviewed to establish an appropriate study drug dose for Part 2.
Subject enrollment for Part 2 will commence upon complete enrollment of Part 1, establishment of an appropriate study drug dose from the PK, and safety analysis of Part 1 and Data Safety Monitoring Board (DSMB) recommendations to proceed to Part 2. Part 2 will enroll approximately 16 subjects, aged 6 months to less than 2 years to obtain information on PK and safety. Subjects will be randomized 1:1 (8 EXPAREL subjects and 8 bupivacaine HCl subjects) to receive either a single dose of EXPAREL or 0.25% bupivacaine HCl using LIA. The overall PK and safety profiles from Part 2 will be completed, analyzed, and reviewed to establish an appropriate study drug dose for Part 3.
Subject enrollment for Part 3 will commence upon complete enrollment of Part 2, establishment of an appropriate study drug dose from the PK and safety analysis of Part 2, and DSMB recommendations to proceed to Part 3.
Part 3 will enroll approximately 16 subjects aged 0 to less than 6 months to obtain information on PK and safety. Subjects will be randomized 1:1 (8 EXPAREL subjects and 8 bupivacaine HCL subjects) to receive either a single dose of EXPAREL or 0.25% bupivacaine HCl using LIA.
Eligibility
Inclusion Criteria:
- Parent/guardian able to speak, read, and understand the language of the ICF and provide informed consent for the subject.
- American Society of Anesthesiologists (ASA) Class 1-3.
- Male or female subjects from 0 to less than 6 years of age on the day of surgery. For Part 1, the subject's age should be 2 years to less than 6 years. For Part 2, the subject's age should be 6 months to less than 2 years. For Part 3, the subject's age should be 0 to less than 6 months.
- Parent/guardian able to adhere to the study visit schedule and complete all study assessments for the subject.
Exclusion Criteria:
- History of hypersensitivity or idiosyncratic reactions or contradictions to bupivacaine HCl or other amide-type local anesthetics or to opioid medications.
- Administration of EXPAREL or bupivacaine HCl within 30 days prior to study drug administration.
- History of coagulopathies or immunodeficiency disorders.
- Clinically significant medical or psychiatric disease that, in the opinion of the investigator, indicates an increased vulnerability to study drugs and/or procedures.
- History of pre-term birth (babies born before 37 weeks of pregnancy).
- Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.
- Concern about a subject's recent or potential exposure to COVID-19, or if the subject is not medically fit/cleared for surgery due to suspected COVID-19 illness/symptoms (or other serious illness).