Study to Evaluate the Pharmacokinetics and Safety of EXPAREL for Postoperative Analgesia in Subjects Undergoing Cardiac Surgery

A Multicenter, Open-label, Randomized, Bupivacaine-Controlled Study to Evaluate the Pharmacokinetics and Safety of EXPAREL for Postoperative Analgesia in Subjects Aged 0 to Less Than 6 Years Undergoing Cardiac Surgery

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).

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: EXPAREL; Drug: bupivacaine

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sarah Shaffer; Phone Number: 973-451-4071; Email: sarah.shaffer@pacira.com

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Health, Riley Hospital For Children
      • Contact: Stephanie Creamean; Phone Number: 7657208423; Email: stephac1@iu.edu
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • St. Louis Children's Hospital (SLCH)
      • Contact: Kyle Stumbaugh; Phone Number: 314-747-0707; Email: kyles@wustl.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Health System
      • Contact: Amy Patrylick; Phone Number: 919-681-2217; Email: amy.petrylick@duke.edu
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • University of Oklahoma (OU) - Medical Center - The Children's Hospital
      • Contact: Amir L Butt, MD, MPH; Phone Number: 36017 (405) 271-8001; Email: abutt@ouhsc.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas Health Science Center at Houston (UTHSC-H) - McGovern Medical School
      • Contact: Emad Sorial; Phone Number: 713-500-6186; Email: Emad.M.Sorial@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All of the following inclusion criteria must be met for eligibility:

1. Pediatric participants with congenital heart defects planned to undergo cardiac surgery with cardiopulmonary bypass
2. Male or female participants from 0 to less than 6 years of age on the day of surgery: 2 years to less than 6 years of age for Part 1; 6 months to less than 2 years of age for Part 2; 0 to less than 6 months of age for Part 3
3. American Society of Anesthesiologists (ASA) Classes 1 through 4.
4. Parent/guardian is able to speak, read, and understand the language of the ICF and provide informed consent for the participant.
5. Parent/guardian is able to adhere to the study visit schedule and complete all study assessments for the participant.

Exclusion Criteria:

Exclusion Criteria:

A participant will not be eligible for the study if any of the following exclusion criteria are met:

1. History of hypersensitivity or idiosyncratic reactions or contradictions to EXPAREL, bupivacaine HCl, or other amide-type local anesthetics or to opioid medications
2. Administration of EXPAREL or bupivacaine HCl within 30 days prior to IP administration
3. Administration of an IP within 30 days or 5 elimination half-lives of such IP, whichever is longer, prior to IP administration, or planned administration of another IP or procedure during participation in this study
4. History of preterm birth (before 35 weeks of pregnancy)
5. History of coagulopathies or immunodeficiency disorders
6. Disease or condition that, in the opinion of the Investigator, indicates an increased vulnerability to IPs and/or procedures
7. Recent or potential exposure to COVID-19
8. Cardiac surgery has been canceled and cannot be rescheduled within 30 days of signing the ICF because of any reason.
9. Necessity in delayed wound closure
10. Informed consent withdrawn before randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EXPAREL; A total of approximately 24 subjects (8 subjects per Part) will be enrolled. Subjects in this arm will receive EXPAREL	Drug: EXPAREL; A single dose of EXPAREL Injectable Product via LIA
Active Comparator: bupivacaine; A total of approximately 24 subjects (8 subjects per Part) will be enrolled. Subjects in this arm will receive bupivacaine	Drug: bupivacaine; A single dose of 0.25% bupivacaine via LIA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The following model-predicted PK endpoint will be determined:	• Area under the plasma concentration-versus-time curve (AUClast and AUC0-inf)	through 72 hours
The following model-predicted PK endpoint will be determined:	• Maximum observed plasma concentration (Cmax)	through 72 hours
The following model-predicted PK endpoint will be determined:	• Time of maximum observed plasma concentration (Tmax)	through 72 hours
The following model-predicted PK endpoint will be determined:	• The apparent terminal elimination half-life (t1/2)	through 72 hours
The following model-predicted PK endpoint will be determined:	• Apparent clearance (CL)	through 72 hours
The following model-predicted PK endpoint will be determined:	• Apparent volume of distribution (Vd)	through 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitals change from Baseline:	temperature	up to 4 postoperative days
Vitals change from Baseline:	heart rate	up to 4 postoperative days
Vitals change from Baseline:	respiratory rate	up to 4 postoperative days
Vitals change from Baseline:	oxygen saturation	up to 4 postoperative days
Vitals change from Baseline:	blood pressure	up to 4 postoperative days
Incidence of treatment-emergent adverse events (TEAEs)		14 ± 3 days
Incidence of adverse events of special interest (AESIs)		14 ± 3 days
Incidence of serious adverse events (SAEs)		14 ± 3 days

Collaborators and Investigators

• Sponsor: Pacira Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 18, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Analgesia; Pediatric; Cardiac Surgery
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Agnosia; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Bupivacaine
• Other Study ID Numbers: 402-C-125

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No