Multicenter Study for Pediatric Subjects Evaluating Pharmacokinetics and Safety of EXPAREL

A Multicenter Study to Evaluate the Pharmacokinetics and Safety of EXPAREL for Postsurgical Analgesia in Pediatric Subjects Aged 6 to Less Than 17 Years

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03682302

Acronym

PLAY

Enrollment

Registered

2018-09-24

Start date

2019-04-02

Completion date

2019-09-24

Last updated

2021-01-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Postoperative Pain Management

Keywords

Pediatric

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.

Interventions

DRUGExparel

EXPAREL 4mg/kg (maximum 266 mg)

DRUG0.5% Bupivacaine HCl

Bupivacaine HCl 2mg/kg

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

6 Years to 17 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame
Area Under the Plasma Concentration-versus-time Curve (AUC) 0 to Infinity	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)
Maximum Plasma Concentration (Cmax)	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)
The Apparent Terminal Elimination Half-life (t1/2el)	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)
Apparent Clearance (CL/F)	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)
Apparent Volume of Distribution (Vd/F)	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)
Area Under the Plasma Concentration-versus-time Curve (AUC) 0 to Tlast	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)

Countries

United States

Participant flow

Recruitment details

Participants were recruited between 02 April 2019 and 24 September 2019 at 15 sites in the US (both Groups).

Participants by arm

Arm	Count
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.	31
Group 1: 12 to Less Than 17 Years, Undergoing Spine Surgery, Bupivacine Single dose of bupivacaine HCl 2 mg/kg (not to exceed a maximum total dose of 175 mg) via local infiltration at the end of spine surgery.	30
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.	5
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.	29
Total	95

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Lost to Follow-up	1	2	0	1
Overall Study	Study drug was not administered	0	0	1	1

Baseline characteristics

Characteristic	Total	Group 2: 6 to Less Than 12 Years, Undergoing Cardiac Surgery, EXPAREL	Group 2: 6 to Less Than 12 Years, Undergoing Spine Surgery, EXPAREL	Group 1: 12 to Less Than 17 Years, Undergoing Spine Surgery, Bupivacine	Group 1: 12 to Less Than 17 Years, Undergoing Spine Surgery, EXPAREL
Age, Continuous	12.1 years STANDARD_DEVIATION 2.81	8.7 years STANDARD_DEVIATION 1.77	10 years STANDARD_DEVIATION 1.73	13.9 years STANDARD_DEVIATION 1.33	13.8 years STANDARD_DEVIATION 1.33
American Society of Anesthesiologists classification ASA 1	28 Participants	0 Participants	1 Participants	13 Participants	14 Participants
American Society of Anesthesiologists classification ASA 2	33 Participants	2 Participants	2 Participants	13 Participants	16 Participants
American Society of Anesthesiologists classification ASA 3	34 Participants	27 Participants	2 Participants	4 Participants	1 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants	9 Participants	0 Participants	7 Participants	10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants	20 Participants	5 Participants	23 Participants	19 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Race (NIH/OMB) Black or African American	11 Participants	2 Participants	1 Participants	3 Participants	5 Participants
Race (NIH/OMB) More than one race	2 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Race (NIH/OMB) White	77 Participants	26 Participants	4 Participants	26 Participants	21 Participants
Region of Enrollment United States	95 participants	29 participants	5 participants	30 participants	31 participants
Sex: Female, Male Female	66 Participants	14 Participants	2 Participants	22 Participants	28 Participants
Sex: Female, Male Male	29 Participants	15 Participants	3 Participants	8 Participants	3 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 31	0 / 30	0 / 5	0 / 29
other Total, other adverse events	19 / 31	22 / 30	5 / 5	9 / 29
serious Total, serious adverse events	0 / 31	0 / 30	0 / 5	2 / 29

Outcome results

Primary

Apparent Clearance (CL/F)

Time frame: 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)