Multicenter Study for Pediatric Subjects Evaluating Pharmacokinetics and Safety of EXPAREL

NCT ID: NCT03682302

Last Updated: 2021-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-02
• Study Completion Date: 2019-09-24

Brief Summary

Primary Objective: To evaluate the pharmacokinetics (PK) of EXPAREL in pediatric subjects aged 6 to less than 17 years undergoing various types of surgeries.

Secondary Objective: To evaluate the safety of EXPAREL in pediatric subjects aged 6 to less than 17 years undergoing various types of surgeries.

Detailed Description

This is a Phase 3, two-part, multi-center, open-label study designed to evaluate the PK and safety profile of EXPAREL in pediatric subjects aged 6 to less than 17 years when administered intraoperatively at the end of surgery via local infiltration. 90 pediatric subjects undergoing spine and/or cardiac surgeries are planned for enrollment.

Part 1 is a multicenter, randomized, open-label study in subjects aged 6 to less than 17 years undergoing spine or cardiac surgeries. There will be 2 treatment groups: Group 1 will include subjects aged 12 to less than 17 years, while Group 2 will include subjects aged 6 to less than 12 years

Part 2 is a multicenter, randomized, open-label, safety study in subjects aged 6 to less than 17 years undergoing spine or cardiac surgeries. There will be 2 treatment groups: Group 1 will include subjects aged 12 to less than 17 years, while Group 2 will include subjects aged 6 to less than 12 years.

Subjects will be screened within 30 days prior to study drug administration. During the screening visit, subjects will be assessed for past or present neurologic, cardiac, and general medical conditions that, in the opinion of the investigator, would preclude them from study participation.

Subjects will undergo their pre-planned spinal or cardiac surgeries per the institution's standard of care. On Day 1, eligible subjects will receive the study drug intraoperatively at the end of surgery via local infiltration into the surgical site. Dosing of EXPAREL will be based on body weight, with a starting dose of 4 mg/kg (maximum 266 mg).

There is no required length of stay in the hospital; subjects may be discharged based on the medical judgment of the treating physician.

A follow-up phone call will be scheduled for all subjects on Day 7. A final follow-up visit will be made on Day 30 to all subjects who would have received the study drug.

Conditions

Postoperative Pain Management

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1: 12 to less than 17 years, undergoing spine surgery, EXPAREL

Single dose of EXPAREL 4 mg/kg (not to exceed a maximum total dose of 266 mg) via local infiltration at the end of spine surgery.

Group Type: EXPERIMENTAL

Exparel

Intervention Type: DRUG

EXPAREL 4mg/kg (maximum 266 mg)

Group 1: 12 to less than 17 years, undergoing spine surgery, bupivacine

Single dose of bupivacaine hydrochloride (HCl) 2 mg/kg (not to exceed a maximum total dose of 175 mg) via local infiltration at the end of spine surgery.

Group Type: ACTIVE_COMPARATOR

0.5% Bupivacaine HCl

Intervention Type: DRUG

Bupivacaine HCl 2mg/kg

Group 2: 6 to less than 12 years, undergoing spine surgery, EXPAREL

Single dose of EXPAREL 4 mg/kg (not to exceed a maximum total dose of 266 mg) via local infiltration at the end of spine surgery.

Group Type: EXPERIMENTAL

Exparel

Intervention Type: DRUG

EXPAREL 4mg/kg (maximum 266 mg)

Group 2: 6 to less than 12 years, undergoing cardiac surgery, EXPAREL

Single dose of EXPAREL 4 mg/kg (not to exceed a maximum total dose of 266 mg) via local infiltration at the end of cardiac surgery.

Group Type: EXPERIMENTAL

Exparel

Intervention Type: DRUG

EXPAREL 4mg/kg (maximum 266 mg)

Interventions

Exparel

EXPAREL 4mg/kg (maximum 266 mg)

Intervention Type: DRUG

0.5% Bupivacaine HCl

Bupivacaine HCl 2mg/kg

Intervention Type: DRUG

Other Intervention Names

Liposomal bupivacaine; Bupivacaine

Eligibility Criteria

Inclusion Criteria

1. Subjects whose parent(s) or guardian(s) has/have signed and dated the ICF for the subject to participate in the study, and subjects who have provided written assent to participate in the study (if capable).

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

3. Male or female subjects 6 to less than 17 years of age on the day of surgery.

4. Body mass index (BMI) at screening within the 5th to 95th percentile for age and sex (see Appendix 5).

5. A negative pregnancy test for female subjects of childbearing potential must be available prior to the start of surgery. The pregnancy test must be conducted in the preoperative holding area according to the study site's standard of care.

6. Subjects and their parent(s)/guardian(s) must be able to speak, read, and understand the language of the ICF and any instruments used for collecting subject-reported outcomes to enable accurate and appropriate responses to study assessments, and provide informed consent/assent.

7. Subjects must be able to adhere to the study visit schedule and complete all study assessments.

Exclusion Criteria

1. Currently pregnant, breastfeeding, or planning to become pregnant during the study or within 1 month after study drug administration.

2. History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or to opioid medication.

3. Contraindication to bupivacaine HCl or other amide-type local anesthetics or to opioid medication.

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

5. Subjects with coagulopathies or immunodeficiency disorders.

6. History of, suspected, or known addiction to or abuse of drugs or alcohol within the past 2 years.

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

8. 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.

In addition, the subject will be ineligible to receive study drug if he or she meets the following criterion during surgery:

9. Any clinically significant event or condition uncovered during the surgery (e.g., excessive bleeding, acute sepsis) that might render the subject medically unstable or complicate the subject's postsurgical course.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pacira Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Igor Grachev, MD, PhD

Role: STUDY_DIRECTOR

Pacira Pharmaceuticals, Inc

Locations

Loma Linda University

Loma Linda, California, United States

Shriners Hospitals for Children, Northern California

Sacramento, California, United States

Stanford University

Stanford, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Nemours / Alfred I. DuPont Hospital for Children

Wilmington, Delaware, United States

Nicklaus Children's Hospital

Miami, Florida, United States

Shriners Hospitals for Children-Chicago

Chicago, Illinois, United States

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, United States

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

McGovern Medical School at UTHealth

Houston, Texas, United States

Southwest Scoliosis Institute

Plano, Texas, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Tirotta CF, de Armendi AJ, Horn ND, Hammer GB, Szczodry M, Matuszczak M, Wang NQ, Scranton R, Ballock RT. A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY). J Clin Anesth. 2021 Dec;75:110503. doi: 10.1016/j.jclinane.2021.110503. Epub 2021 Sep 14.

Reference Type: DERIVED

PMID: 34534923 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

402-C-319

Identifier Type: -

Identifier Source: org_study_id