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

Postoperative Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06271265
• Other study ID #: 402-C-125
• Status: Recruiting
• Phase: Phase 1
• Start date: March 29, 2024
• Est. completion date: July 2025

Study information

• Verified date: June 2024
• Source: Pacira Pharmaceuticals, Inc
• Contact: Sarah Shaffer
• Phone: 973-451-4071
• Email: sarah.shaffer[@]pacira.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 6 Years

Eligibility

Inclusion Criteria:

1. Parent/guardian able to speak, read, and understand the language of the ICF and provide informed consent for the subject.

2. American Society of Anesthesiologists (ASA) Class 1-3.

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.

4. Parent/guardian able to adhere to the study visit schedule and complete all study assessments for the subject.

Exclusion Criteria:

1. History of hypersensitivity or idiosyncratic reactions or contradictions to bupivacaine HCl or other amide-type local anesthetics or to opioid medications.

2. Administration of EXPAREL or bupivacaine HCl within 30 days prior to study drug administration.

3. History of coagulopathies or immunodeficiency disorders.

4. Clinically significant medical or psychiatric disease that, in the opinion of the investigator, indicates an increased vulnerability to study drugs and/or procedures.

5. History of pre-term birth (babies born before 37 weeks of pregnancy).

6. 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.

7. 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).

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• EXPAREL
A single dose of EXPAREL Injectable Product via LIA
• bupivacaine
A single dose of 0.25% bupivacaine via LIA

Locations

Country	Name	City	State
United States	The University of Texas Health Science Center at Houston (UTHSC-H) - McGovern Medical School	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Pacira Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The following model-predicted PK endpoint will be determined:	• Area under the plasma concentration-versus-time curve (AUClast and AUC0-inf)	through 72 hours
Primary	The following model-predicted PK endpoint will be determined:	• Maximum observed plasma concentration (Cmax)	through 72 hours
Primary	The following model-predicted PK endpoint will be determined:	• Time of maximum observed plasma concentration (Tmax)	through 72 hours
Primary	The following model-predicted PK endpoint will be determined:	• The apparent terminal elimination half-life (t1/2)	through 72 hours
Primary	The following model-predicted PK endpoint will be determined:	• Apparent clearance (CL)	through 72 hours
Primary	The following model-predicted PK endpoint will be determined:	• Apparent volume of distribution (Vd)	through 72 hours
Secondary	Vitals change from Baseline:	temperature	up to 4 postoperative days
Secondary	Vitals change from Baseline:	heart rate	up to 4 postoperative days
Secondary	Vitals change from Baseline:	respiratory rate	up to 4 postoperative days
Secondary	Vitals change from Baseline:	oxygen saturation	up to 4 postoperative days
Secondary	Vitals change from Baseline:	blood pressure	up to 4 postoperative days
Secondary	Incidence of treatment-emergent adverse events (TEAEs)		14 ± 3 days
Secondary	Incidence of adverse events of special interest (AESIs)		14 ± 3 days
Secondary	Incidence of serious adverse events (SAEs)		14 ± 3 days