Clinical trial NCT03682302: Multicenter Study for Pediatric Subjects Evaluating Pharmacokinetics and Safety of EXPAREL
Official title: A Multicenter Study to Evaluate the Pharmacokinetics and Safety of EXPAREL for Postsurgical Analgesia in Pediatric Subjects Aged 6 to Less Than 17 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Pain Management
Keywords: Pediatric
Lead sponsor: Pacira Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2018-09-24
Enrollment: 98
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Area Under the Plasma Concentration-versus-time Curve (AUC) 0 to Infinity
timeFrame: 15, 30, 45 min, 1-1.25h, 2-4h, 10-18h, 24-36h, 42-60h (spine surgery) or 15, 30, 45 min, 1-1.25, 15-25, 20-40, 45-55, 64-72h (cardiac surgery)
measure: Maximum Plasma Concentration (Cmax)
timeFrame: 15, 30, 45 min, 1-1.25h, 2-4h, 10-18h, 24-36h, 42-60h (spine surgery) or 15, 30, 45 min, 1-1.25, 15-25, 20-40, 45-55, 64-72h (cardiac surgery)
measure: The Apparent Terminal Elimination Half-life (t1/2el)
timeFrame: 15, 30, 45 min, 1-1.25h, 2-4h, 10-18h, 24-36h, 42-60h (spine surgery) or 15, 30, 45 min, 1-1.25, 15-25, 20-40, 45-55, 64-72h (cardiac surgery)
measure: Apparent Clearance (CL/F)
timeFrame: 15, 30, 45 min, 1-1.25h, 2-4h, 10-18h, 24-36h, 42-60h (spine surgery) or 15, 30, 45 min, 1-1.25, 15-25, 20-40, 45-55, 64-72h (cardiac surgery)
measure: Apparent Volume of Distribution (Vd/F)
timeFrame: 15, 30, 45 min, 1-1.25h, 2-4h, 10-18h, 24-36h, 42-60h (spine surgery) or 15, 30, 45 min, 1-1.25, 15-25, 20-40, 45-55, 64-72h (cardiac surgery)
measure: Area Under the Plasma Concentration-versus-time Curve (AUC) 0 to Tlast
timeFrame: 15, 30, 45 min, 1-1.25h, 2-4h, 10-18h, 24-36h, 42-60h (spine surgery) or 15, 30, 45 min, 1-1.25, 15-25, 20-40, 45-55, 64-72h (cardiac surgery)
Secondary outcomes:
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Sacramento
country: United States
facility: Shriners Hospitals for Children, Northern California
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Nemours / Alfred I. DuPont Hospital for Children
state: Delaware
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Shriners Hospitals for Children-Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Children's Hospital
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: McGovern Medical School at UTHealth
state: Texas
city: Plano
country: United States
facility: Southwest Scoliosis Institute
state: Texas
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Pacira Pharmaceuticals, Inc
name: Igor Grachev, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.