EXPAREL for Postoperative Pain

Recruiting at 2 trial locations

Overseen By Sarah Shaffer

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Pacira Pharmaceuticals, Inc

Must not be taking: Opioids, Amide anesthetics

Disqualifiers: Coagulopathies, Immunodeficiency, Pre-term birth, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

48 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications, but it does exclude those who have taken EXPAREL or bupivacaine HCl within 30 days before the study. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug EXPAREL for postoperative pain?

Clinical trials have shown that EXPAREL, an extended-release form of bupivacaine, provides pain relief for up to 3-4 days after surgery and reduces the need for additional pain medication. ^{1 2 3 4 5}

Is EXPAREL (liposomal bupivacaine) generally safe for humans?

Research shows that EXPAREL, a form of bupivacaine, has been studied for safety in various uses. It has a favorable cardiac safety profile and similar tissue reaction to other bupivacaine solutions, with no detected nerve damage in studies. However, some inflammation and muscle damage were noted, so monitoring for local tissue injury is important. ^{1 3 5 6 7}

What makes the drug EXPAREL unique for postoperative pain management?

EXPAREL is unique because it is an extended-release form of the local anesthetic bupivacaine, designed to provide pain relief for up to 3-4 days with a single injection at the surgical site, reducing the need for additional opioid pain medications. ^{1 2 3 8 9}

What is the purpose of this trial?

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).

Eligibility Criteria

This trial is for children aged 0 to less than 6 years undergoing cardiac surgery. Their guardians must understand the consent form and agree to follow the study's schedule. Children should be healthy enough for anesthesia (ASA Class 1-3). Different age groups will be studied in separate parts of the trial.

Inclusion Criteria

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

American Society of Anesthesiologists (ASA) Class 1-3

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

Exclusion Criteria

I have a history of blood clotting or immune system disorders.

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

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1 Treatment

Subjects aged 2 to less than 6 years receive a single dose of EXPAREL or bupivacaine HCl for PK and safety evaluation

1 week

1 visit (in-person)

Part 2 Treatment

Subjects aged 6 months to less than 2 years receive a single dose of EXPAREL or bupivacaine HCl for PK and safety evaluation

1 week

1 visit (in-person)

Part 3 Treatment

Subjects aged 0 to less than 6 months receive a single dose of EXPAREL or bupivacaine HCl for PK and safety evaluation

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• bupivacaine
• EXPAREL

Trial Overview The study compares EXPAREL, a long-lasting pain reliever, with bupivacaine, a common local anesthetic, in young patients after heart surgery. It aims to see how these drugs are processed by the body and how safe they are when used for pain control.

Participant Groups

Group I: EXPAREL Experimental Treatment 1 Intervention

A total of approximately 24 subjects (8 subjects per Part) will be enrolled. Subjects in this arm will receive EXPAREL

Group II: bupivacaine Active Control 1 Intervention

A total of approximately 24 subjects (8 subjects per Part) will be enrolled. Subjects in this arm will receive bupivacaine

EXPAREL is already approved in United States for the following indications:

Approved in United States as Exparel for:

• Postsurgical local analgesia via infiltration in patients aged 6 years and older
• Postsurgical regional analgesia in adults via interscalene brachial plexus nerve block

Who Is Running the Clinical Trial?

Pacira Pharmaceuticals, Inc

Lead Sponsor

Trials

142

Recruited

14,300+

Headquarters

Tampa, USA

Known For

Non-opioid Pain Management

Top Products

Exparel, Zilretta, iovera

Dr. Jonathan Slonin

Pacira Pharmaceuticals, Inc

Chief Medical Officer since 2020

BSc in Biomedical Engineering and MD from University of Miami, MBA from George Washington University

Frank D. Lee

Pacira Pharmaceuticals, Inc

Chief Executive Officer since 2024

BSc in Chemical Engineering from Vanderbilt University, MBA from Wharton Graduate School of Business

Findings from Research

In a retrospective analysis of 575 subjects across 6 clinical trials, liposome bupivacaine showed a similar safety profile to both bupivacaine HCl and normal saline, with 76% of liposome bupivacaine recipients experiencing adverse events (AEs).

The most common AEs for liposome bupivacaine included nausea and hypesthesia, and serious AEs occurred in 8% of subjects, indicating that the side effects are likely related to the surgical procedure rather than the medication itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. Ilfeld, BM., Viscusi, ER., Hadzic, A., et al.[2022]

DepoFoam bupivacaine, an extended-release formulation of the local anesthetic bupivacaine, provides effective pain relief for 3-4 days after a single administration at the surgical site, reducing the need for opioid pain relief.

The safety profile of DepoFoam bupivacaine is comparable to traditional bupivacaine HCl, with adverse events being dose-related, indicating it is a safe option for managing postsurgical pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of DepoFoam(®) bupivacaine for the treatment of postsurgical pain. Bergese, SD., Onel, E., Portillo, J.[2014]

In a study involving 98 mice, liposomal bupivacaine (Exparel®) provided a longer duration of pain relief compared to standard bupivacaine, with motor block lasting up to 180 minutes and thermoalgesic block lasting up to 420 minutes.

The addition of dexamethasone, either perineurally or systemically, significantly reduced neural inflammation caused by bupivacaine, and perineural dexamethasone also helped reduce inflammation from Exparel®, suggesting a protective effect against nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo. Ferré, F., Krin, A., Sanchez, M., et al.[2020]

In a phase 3 study involving 189 patients undergoing hemorrhoidectomy, bupivacaine extended-release significantly reduced pain intensity scores compared to placebo, indicating its efficacy in providing long-lasting postoperative analgesia.

Patients receiving bupivacaine extended-release were more likely to remain opioid-free for longer periods and reported higher satisfaction with pain management, highlighting its potential to reduce opioid consumption after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Gorfine, SR., Onel, E., Patou, G., et al.[2022]

In a pilot study involving 25 pigs, subarachnoid administration of liposomal bupivacaine resulted in a longer duration of pain relief compared to standard bupivacaine hydrochloride, with effects lasting up to 32 hours for higher doses.

No signs of neurotoxicity were observed in any treatment group, suggesting that liposomal bupivacaine may be a safe option for extended analgesia in the neuraxial space, warranting further studies for potential human use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study. Zel, J., Hadzic, A., Cvetko, E., et al.[2019]

In a phase 2 study involving 138 patients undergoing total knee arthroplasty, bupivacaine extended-release liposome injection showed no significant changes in ECG parameters, such as QRS and QTcF durations, indicating a favorable cardiac safety profile.

Across multiple studies with a total of 1459 patients, no clinically relevant cardiac adverse events were associated with bupivacaine extended-release, suggesting it is safe for use in postsurgical pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine extended-release liposome injection exhibits a favorable cardiac safety profile. Bergese, SD., Onel, E., Morren, M., et al.[2019]

Exparel™ (DepoFoam bupivacaine) provides a longer-lasting nerve blockade (240 minutes) compared to standard bupivacaine solutions, which lasted 120 minutes and 210 minutes, indicating its potential for improved pain management.

While Exparel™ showed slightly higher inflammation scores than standard bupivacaine solutions shortly after injection, it had similar myotoxicity levels and no neurotoxicity, suggesting it may be a safe option for local anesthesia, though monitoring for tissue reactions is recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multivesicular liposomal bupivacaine at the sciatic nerve. McAlvin, JB., Padera, RF., Shankarappa, SA., et al.[2022]

EXPAREL® (bupivacaine liposome injectable suspension) is an effective extended-release local anesthetic that can significantly improve postoperative pain management in orthopedic trauma surgery, as demonstrated in two case studies.

Both patients treated with EXPAREL® experienced good control of postsurgical pain, highlighting its safety and efficacy as part of a multimodal analgesia approach in reducing the risk of chronic pain after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local infiltration of liposome bupivacaine in orthopedic trauma patients: case-based reviews. Hutchinson, HL.[2022]

EXPAREL® (bupivacaine liposome injectable suspension) is an FDA-approved extended-release anesthetic that significantly reduces postoperative pain and opioid consumption in patients undergoing total knee and hip replacement surgeries, as shown in multiple phase 2 and phase 3 studies.

Using EXPAREL® as part of a multimodal pain management approach leads to better outcomes, including lower pain scores, reduced need for rescue opioids, and improved patient satisfaction during recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in incorporation of local analgesics in postsurgical pain pathways. Lombardi, AV.[2014]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Evaluation of DepoFoam(®) bupivacaine for the treatment of postsurgical pain. [2014]

3. England pubmed.ncbi.nlm.nih.gov

Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Bupivacaine extended-release liposome injection exhibits a favorable cardiac safety profile. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Multivesicular liposomal bupivacaine at the sciatic nerve. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Local infiltration of liposome bupivacaine in orthopedic trauma patients: case-based reviews. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Recent advances in incorporation of local analgesics in postsurgical pain pathways. [2014]