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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of Liposomal Bupivacaine, a type of anesthetic, when given as a single spinal injection. Researchers seek to understand how this drug behaves in the body and its effects after administration. Participants will be divided into groups to receive either the experimental drug, a standard anesthetic, or a placebo (a harmless substance with no active drug). Healthy adults without frequent headaches or back issues are ideal candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that liposomal bupivacaine can cause common side effects such as nausea, fever, itching, constipation, and vomiting. Reports have documented serious allergic reactions, including anaphylaxis, a severe and potentially life-threatening reaction requiring immediate medical attention. An analysis of real-world data identified 58 safety signals for liposomal bupivacaine, indicating it may cause certain side effects, some of which are not officially approved uses. Despite this, liposomal bupivacaine is already used in medical settings, suggesting it is safe when used correctly. Consider these findings if thinking about joining a trial involving this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Liposomal Bupivacaine 13.3 is unique because it uses a liposomal delivery system to extend the release of bupivacaine, potentially offering longer-lasting pain relief compared to standard bupivacaine. Researchers are excited about this treatment because it could reduce the need for repeated dosing, enhancing convenience and comfort for patients. Unlike other treatments that provide shorter pain relief durations, Liposomal Bupivacaine 13.3 might sustain its effects over an extended period, making it an appealing option for managing pain efficiently.

What evidence suggests that this trial's treatments could be effective?

Research shows that liposomal bupivacaine, studied in this trial, offers a promising option for managing pain. In surgeries like hernia repairs and bunion removals, it has controlled pain more effectively than regular bupivacaine. Studies have found that liposomal bupivacaine reduces pain in the first 24 hours after surgery. However, some research found no major difference in overall recovery compared to regular bupivacaine. Its special formulation releases the medication slowly, providing longer-lasting pain relief, making it a strong choice for effective pain control. In this trial, participants will receive either liposomal bupivacaine, regular bupivacaine, or a placebo to further evaluate its effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Sergey Zaets

Principal Investigator

Pacira Pharmaceuticals, Inc

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3772762/

Liposomal extended-release bupivacaine for postsurgical ... EXPAREL® has been found to be a more effective pain management treatment than standard bupivacaine in inguinal hernia repair, bunionectomy, hemorrhoidectomy, ...

2. withpower.com withpower.com/trial/phase-1-healthy-subjects-hs-7-2022-1b8be

Liposomal Bupivacaine for Healthy Volunteers In a study involving 823 patients across various surgical settings, liposome bupivacaine demonstrated a lower incidence of adverse events (62%) compared to ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02662036

Analgesic Efficacy of Liposomal Bupivacaine vs. ... Study Overview. This study will evaluate the efficacy of analgesia provided by liposomal bupivacaine (Exparel) when compared to bupivacaine HCL as a transverse ...

4. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2790975

Efficacy of Liposomal Bupivacaine and ... This study found that liposomal bupivacaine did not improve postoperative recovery or pain compared with bupivacaine hydrochloride alone among patients ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12277084/

Clinical Effectiveness of Perineural Liposomal Bupivacaine is ... Local infiltration analgesia with liposomal bupivacaine improves early outcomes after total knee arthroplasty: 24-hour data from the PILLAR ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/022496s9lbl.pdf

EXPAREL (bupivacaine liposome injectable suspension) The safety and effectiveness of bupivacaine and other amide-containing products depend on proper dosage, correct technique, adequate precautions, and readiness ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26204387/

Safety and Side Effect Profile of Liposome Bupivacaine ... The most frequently reported AEs among subjects receiving liposome bupivacaine were nausea, pyrexia, pruritus, constipation, and vomiting. The most common ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/bupivacaine-liposome-injection-route/description/drg-20075313

Bupivacaine liposome (injection route) - Side effects & uses This medicine may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and require immediate medical attention ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11975001/

Real-World Pharmacovigilance Analysis of Adverse Events ... The analysis revealed 8,023 AE reports in total. Liposomal bupivacaine had 58 positive safety signals, 24 of which were off-label and listed in ...

10. drugs.com drugs.com/mtm/bupivacaine-liposome.html

Bupivacaine liposome Uses, Side Effects & Warnings Bupivacaine liposome side effects ; ringing in your ears;. drowsiness, feeling restless or anxious; ; ongoing numbness, weakness, or loss of ...