Liposomal Bupivacaine for Healthy Volunteers

Overseen By Lisa Ramsay

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Pacira Pharmaceuticals, Inc

Must not be taking: Opioids, NSAIDs, Corticosteroids, Neuromodulators

Disqualifiers: Headaches, Back pain, Renal impairment, others

Compensation: Varies

Number of Visits: 6

Duration: 1 week

54 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking opioid medications and NSAIDs (non-steroidal anti-inflammatory drugs) at least 3 days before the study drug is given. If you are on neuromodulating agents for pain control, you cannot participate, but if you take them for other reasons, you must be on a stable dose for at least 1 month before the study.

What data supports the effectiveness of the drug Liposomal Bupivacaine 13.3?

Liposomal Bupivacaine is shown to provide pain relief for up to 72 hours after surgery, as it is designed to release the medication slowly over time. It has been used effectively for pain management in surgical settings, such as lumbar fusions, and is approved by the FDA for this purpose. ^{1 2 3 4 5}

Is liposomal bupivacaine safe for humans?

Liposomal bupivacaine has been shown to be safe in various studies, including those involving healthy volunteers and surgical patients. It has been approved by the FDA for managing postsurgical pain and has demonstrated safety across different procedures. ^{2 4 6 7 8}

How is liposomal bupivacaine different from other drugs?

Liposomal bupivacaine is unique because it is a special formulation that releases the drug slowly over 72 hours, providing longer-lasting pain relief compared to regular bupivacaine. This makes it particularly useful for managing pain after surgery. ^{1 2 4 5 9}

What is the purpose of this trial?

This trial tests a new slow-release pain-relief drug called Liposomal Bupivacaine 13.3 in healthy adults to ensure it is safe and well-tolerated. Liposomal bupivacaine is designed to provide extended postsurgical pain relief and reduce opioid consumption.

Research Team

Sergey Zaets

Principal Investigator

Pacira Pharmaceuticals, Inc

Eligibility Criteria

Healthy adults aged 18-50, with no history of severe headaches, back conditions, or chronic pain. Participants must not have allergies to study medications like bupivacaine and should not be on certain medications like corticosteroids before the trial. Women must not be pregnant or nursing.

Inclusion Criteria

American Society of Anesthesiologists physical status 1

Able to provide informed consent, adhere to the study schedule, and complete all study assessments

Exclusion Criteria

I have a bleeding risk or a blood clotting disorder with low platelets.

I am not allergic or intolerant to the study's medications.

Currently pregnant, nursing, or planning to become pregnant during the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intrathecal injection of Liposomal Bupivacaine 13.3, bupivacaine, or placebo, followed by a 5-day stay in the Early Phase Research Unit

1 week

5 days in Early Phase Research Unit

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a follow-up visit on Day 9 and a phone call on Day 30

4 weeks

1 visit (in-person), 1 phone call

Treatment Details

Interventions

• Liposomal Bupivacaine 13.3

Trial Overview The safety and effects of Liposomal Bupivacaine 13.3 are being tested when given as a single spinal injection to healthy volunteers. The trial will also measure how the drug moves through and affects the body.

Participant Groups

Group I: Liposomal Bupivacaine 13.3 Experimental Treatment 1 Intervention

Cohort 1 subjects will be dosed 2 mL (26.6 mg) of Liposomal Bupivacaine 13.3. Cohort 2 subjects randomized to the Liposomal Bupivacaine 13.3 arm will be dosed 3 mL (39.9 mg) of Liposomal Bupivacaine 13.3. Cohort 3 subjects randomized to the Liposomal Bupivacaine 13.3 arm will be dosed 4 mL (53.2 mg) of Liposomal Bupivacaine 13.3.

Group II: Bupivacaine IT Active Control 1 Intervention

Cohort 1 subjects randomized to the bupivacaine arm will be dosed 2 mL (7.5 mg/ 1 mL) of 0.75% bupivacaine. Cohort 2 subjects randomized to the bupivacaine arm will be dosed 2 mL (7.5 mg/ 1 mL) of 0.75% bupivacaine mixed with 1 mL of preservative free normal saline to create a total volume of solution administered of 3 mL. Cohort 3 subjects randomized to the bupivacaine arm will be dosed 2 mL (7.5 mg / 1 mL) of 0.75% bupivacaine mixed with 2 mL of preservative free normal saline to create a total volume of solution administered of 4 mL.

Group III: Placebo Placebo Group 1 Intervention

Cohort 1 subjects randomized to the placebo arm will be dosed 2 mL of preservative free normal saline. Cohort 2 subjects randomized to the placebo arm will be dosed 3 mL of preservative free normal saline. Cohort 3 subjects randomized to the placebo arm will be dosed 4 mL of preservative free normal saline.

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

Liposomal bupivacaine, administered in single or repeated doses, showed a maximum plasma concentration (C max) that remained well below the toxicity thresholds for neurotoxicity and cardiac toxicity, indicating a strong safety profile.

The study demonstrated that both single and repeated doses of liposomal bupivacaine were well-tolerated in healthy volunteers, with no significant adverse effects on neurologic or cardiac function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers. Rice, D., Heil, JW., Biernat, L.[2018]

In a study involving 823 patients across various surgical settings, liposome bupivacaine demonstrated a lower incidence of adverse events (62%) compared to bupivacaine HCl (75%) and placebo (43%), indicating better tolerability.

Serious adverse events were less common in the liposome bupivacaine group (2.7%) compared to bupivacaine HCl (5.4%), suggesting that liposome bupivacaine may be a safer option for local analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of liposome bupivacaine, a novel local analgesic formulation. Viscusi, ER., Sinatra, R., Onel, E., et al.[2022]

In a randomized controlled trial involving 57 patients undergoing midurethral sling placement, liposomal bupivacaine resulted in lower median pain scores on postoperative day 1 compared to a mixture of bupivacaine and lidocaine (20 mm vs 30 mm), indicating some efficacy in pain management.

Despite the initial lower pain scores, there were no significant differences in overall opioid and nonsteroidal anti-inflammatory drug consumption or in quality of recovery scores after 7 days, suggesting that liposomal bupivacaine may not provide a clinically significant advantage over traditional pain management methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Versus Bupivacaine Hydrochloride with Lidocaine during Midurethral Sling Placement: A Randomized Controlled Trial. Iwanoff, C., Salamon, C.[2020]

In a study of 34 patients undergoing breast augmentation, liposomal bupivacaine provided statistically significant lower pain scores compared to standard bupivacaine at multiple time points post-surgery, indicating it may offer better pain control.

Despite the statistical significance, the differences in pain relief were small, and 70% of patients felt the additional cost of liposomal bupivacaine was not justified by the benefits, suggesting limited clinical relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. Nadeau, MH., Saraswat, A., Vasko, A., et al.[2022]

Bupivacaine liposomal injection has been approved by the FDA as a local anesthetic for managing postsurgical pain in adults, showing significant efficacy in reducing postoperative pain and opioid use compared to placebo.

This review compares the efficacy of bupivacaine liposomal to conventional bupivacaine with or without epinephrine, utilizing both published and unpublished data submitted to the FDA by the manufacturer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine liposomal versus bupivacaine: comparative review. Noviasky, J., Pierce, DP., Whalen, K., et al.[2021]

In a study of 50 patients undergoing vaginal reconstructive surgery, liposomal bupivacaine (LB) did not show any significant advantage over plain bupivacaine in terms of postoperative pain control, narcotic use, or length of hospital stay.

Despite LB's higher cost, the results indicate that it is not more effective than plain bupivacaine for managing pain after surgery, suggesting a need for further research to find the best pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal versus plain bupivacaine for pain control following vaginal reconstruction. Jensen, S., Amasyali, AS., Keheila, M., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers. [2018]

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

The safety of liposome bupivacaine, a novel local analgesic formulation. [2022]

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

Liposomal Bupivacaine Versus Bupivacaine Hydrochloride with Lidocaine during Midurethral Sling Placement: A Randomized Controlled Trial. [2020]

4. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetics and pharmacodynamics of liposome bupivacaine administered via a single epidural injection to healthy volunteers. [2022]

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

Retrospective Assessment of the Use of Liposomal Bupivacaine in Lumbar Fusions in Immediate Postoperative Hospital Care. [2021]

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

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. [2022]

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

Bupivacaine liposomal versus bupivacaine: comparative review. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of liposomal bupivacaine after local infiltration in healthy Chinese adults: a phase 1 study. [2022]

9. Canada pubmed.ncbi.nlm.nih.gov

Liposomal versus plain bupivacaine for pain control following vaginal reconstruction. [2023]