CLINICAL TRIALS PROFILE FOR BUPIVACAINE HYDROCHLORIDE

505(b)(2) Clinical Trials for bupivacaine hydrochloride

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT01349140 ↗	EXPAREL Dose-Response for Single-Injection Femoral Nerve Blocks	Completed	Pacira Pharmaceuticals, Inc	Phase 1	2012-02-01	EXPAREL™, an investigational drug product, is a new formulation of a local anesthetic (numbing medicine) that is designed to be longer acting than the currently-available local anesthetics. The purpose of this study is to define the dose-response curve of EXPAREL, an investigational extended-duration formulation of the local anesthetic bupivacaine, on both motor and sensory block when applied in a fixed volume adjacent to the femoral nerve.
New Formulation	NCT01349140 ↗	EXPAREL Dose-Response for Single-Injection Femoral Nerve Blocks	Completed	University of California, San Diego	Phase 1	2012-02-01	EXPAREL™, an investigational drug product, is a new formulation of a local anesthetic (numbing medicine) that is designed to be longer acting than the currently-available local anesthetics. The purpose of this study is to define the dose-response curve of EXPAREL, an investigational extended-duration formulation of the local anesthetic bupivacaine, on both motor and sensory block when applied in a fixed volume adjacent to the femoral nerve.
OTC	NCT02929589 ↗	Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy	Suspended	Mike O'Callaghan Federal Hospital	Phase 3	2018-07-05	This is a prospective, randomized, double-blinded, and placebo-controlled trial comparing oxycodone/acetaminophen prescribed with or without ibuprofen for pain control following open unilateral inguinal hernia repair, with allowed exception of any currently prescribed opioid (codeine, hydrocodone, hydromorphone, morphine, methadone, oxymorphone, transdermal fentanyl), which can be continued. The patients will not be allowed to continue any over-the-counter pain medications, such as ibuprofen, naproxen, or acetaminophen containing medications, that were not prescribed by the investigators during this study. Patients not receiving Ibuprofen will be given a placebo pill composed of corn starch. The placebo pill will be formulated into the same shape, size and color as the ibuprofen capsule. Neither the investigators nor the research subjects will know if the subject is receiving a placebo versus Ibuprofen. The subjects will complete pain level and medication diaries, and will be followed for 2 months after their surgery. The research aims to discover the appropriate amount of opioid medication to prescribe to patients undergoing an elective open inguinal hernia repair, and reduce the total opioid dose needed by utilizing ibuprofen in combination. The investigators expect that the subjects who take ibuprofen will use less oxycodone/acetaminophen, and have comparable or lower mean pain levels. This could contribute to reducing the surplus opioids prescribed by physicians after surgery, which can lead to opioid use disorders. This particular procedure is common in men, and the findings have the potential to decrease the symptoms and pain of Active Duty members and DoD beneficiaries who undergo an inguinal hernia repair, and are at risk for prescription drug abuse or dependence.
OTC	NCT02929589 ↗	Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy	Suspended	Mike O'Callaghan Military Hospital	Phase 3	2018-07-05	This is a prospective, randomized, double-blinded, and placebo-controlled trial comparing oxycodone/acetaminophen prescribed with or without ibuprofen for pain control following open unilateral inguinal hernia repair, with allowed exception of any currently prescribed opioid (codeine, hydrocodone, hydromorphone, morphine, methadone, oxymorphone, transdermal fentanyl), which can be continued. The patients will not be allowed to continue any over-the-counter pain medications, such as ibuprofen, naproxen, or acetaminophen containing medications, that were not prescribed by the investigators during this study. Patients not receiving Ibuprofen will be given a placebo pill composed of corn starch. The placebo pill will be formulated into the same shape, size and color as the ibuprofen capsule. Neither the investigators nor the research subjects will know if the subject is receiving a placebo versus Ibuprofen. The subjects will complete pain level and medication diaries, and will be followed for 2 months after their surgery. The research aims to discover the appropriate amount of opioid medication to prescribe to patients undergoing an elective open inguinal hernia repair, and reduce the total opioid dose needed by utilizing ibuprofen in combination. The investigators expect that the subjects who take ibuprofen will use less oxycodone/acetaminophen, and have comparable or lower mean pain levels. This could contribute to reducing the surplus opioids prescribed by physicians after surgery, which can lead to opioid use disorders. This particular procedure is common in men, and the findings have the potential to decrease the symptoms and pain of Active Duty members and DoD beneficiaries who undergo an inguinal hernia repair, and are at risk for prescription drug abuse or dependence.

All Clinical Trials for bupivacaine hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001088 ↗	A Phase I Safety and Immunogenicity Trial of the Facilitated HIV-1 Gag-Pol DNA Vaccine (APL-400-047, Apollon, Inc.) Given Intramuscularly by Needle and Syringe or Biojector 2000 Needle-Free Jet Injection System in HIV-1 Uninfected Adult Volunteers	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1997-07-01	To evaluate the safety, tolerability and immunogenicity in humans of the APL-400-047 vaccine when administered intramuscularly by needle and syringe at 1 of 3 doses or by Biojector at the intermediate dose. [AS PER AMENDMENT 07/98: To evaluate the tolerability, safety, and immunogenicity of an increased dose in an additional group of volunteers.] DNA-based immunization mimics live-attenuated virus vaccination by stimulation of both the humoral and cellular arms of the immune system; thus, potentially providing the advantages of a live virus vaccination but without the potential risks. It is essential that novel vaccine strategies (including DNA-based immunizations) continue to be developed and enter Phase I human testing because to date, no candidate vaccine from any of the approximately 30 AVEG Phase I or II trials has progressed to a Phase III efficacy trial. Use of a Biojector jet gun for vaccine delivery may also have potential psychological, comfort, safety and immunologic advantages over the traditional needle and syringe method of delivery.
NCT00001090 ↗	A Multicenter, Randomized, Placebo-Controlled, Double-Blinded, Phase I Trial to Evaluate the Safety and Immunogenicity of Live Recombinant Canarypox ALVAC-HIV vCP205 Combined With GM-CSF in Healthy, HIV-1 Uninfected Volunteers	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1969-12-31	To evaluate the safety and immunogenicity of live recombinant canarypox ALVAC-HIV vCP205 in combination with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) at 80 microg and 250 microg. [AS PER AMENDMENT 4/30/99: To study the safety of following 4 ALVAC immunizations with a nucleic acid gag/pol HIV-1 immunogen (APL-400-047, Wyeth-Lederle). To assess the ability of this sequence of immunization to boost the LTL, T-helper cell, and antibody response.] ALVAC-HIV candidate vaccines have induced HIV-specific CTL responses in more than half of recipients in some protocols. Depending on the HIV-1 gene products expressed by the particular ALVAC-HIV candidate vaccine, volunteers have generated anti-Envelope (vCP125, vCP205, and vCP300), anti-Gag (vCP205 and vCP300), and anti-Nef (vCP300) CTL activity. Although 3 to 4 immunizations with the different ALVAC-HIV experimental vaccines induce anti-HIV-1 neutralizing antibodies in a portion, often the majority, of volunteers, the geometric mean titers of these antibodies are modest, usually less than 50. This study will determine whether there is an increase in the anti-HIV antibody titers when GM-CSF is used as an adjuvant with ALVAC-HIV vCP205 and will also examine the kinetics and magnitude of the HIV-specific CTL response.
NCT00001724 ↗	Local Flurbiprofen to Treat Pain Following Wisdom Tooth Extraction	Completed	National Institute of Dental and Craniofacial Research (NIDCR)	Phase 2	1997-11-01	This study will evaluate the effectiveness of the non-steroidal anti-inflammatory drug flurbiprofen (Ansaid® (Registered Trademark)) in relieving pain following oral surgery. Flurbiprofen is approved by the Food and Drug Administration for treatment of arthritis pain. Patients 16 years of age and older requiring third molar (wisdom tooth) extraction may be eligible for this study. Patients will undergo oral surgery to remove two lower third molar teeth. Before surgery, they will be given a local anesthetic (lidocaine with epinephrine) injected in the mouth and a sedative (Versed) infused through a catheter (thin plastic tube) placed in an arm vein. At the time of surgery, patients will also be given flurbiprofen or a placebo formulation (look-alike substance with no active ingredient) directly into the extraction site and a capsule that also may contain flurbiprofen or placebo. One in seven patients will receive only placebo. All patients will fill out pain questionnaires and stay in the clinic for up to 6 hours for observation of bleeding and medication side effects. Patients who do not have satisfactory pain relief from the test medicine after surgery may request a standard pain reliever. A small blood sample will be collected during surgery and at 15 minutes, one-half hour and 1, 2, 3, 4, 5, 6, 24 and 48 hours after surgery to measure flurbiprofen blood levels. A total of 33 ml (about 2 tablespoons) of blood will be drawn for these tests. Samples collected on the day of surgery will be drawn from the catheter used to administer the sedative; the 24- and 48-hour samples will be taken by needle from an arm or hand vein. Urine samples will also be collected between 4 and 6 hours after surgery and again at 24 and 48 hours after surgery.
NCT00008476 ↗	Capsaicin to Control Pain Following Third Molar Extraction	Completed	National Institute of Dental and Craniofacial Research (NIDCR)	Phase 2	2001-01-01	This study will test the effectiveness of the drug capsaicin in controlling pain after third molar (wisdom tooth) extraction. Capsaicin, the ingredient in chili peppers that makes them "hot," belongs to a class of drugs called vanilloids, which have been found to temporarily inactivate pain-sensing nerves. Healthy normal volunteers between 16 and 40 years of age who require third molar (wisdom tooth) extraction may be eligible for this study. Participants will undergo the following procedures in three visits: Visit 1: Patients will have touch (sensory) testing by the following three methods: 1) a warm sensor applied to the gums and the patient will rate when they first feel heat and when the heat feels painful; 2) the bristles of a small paint brush will be gently stroked across the gums, and the patient will say whether it feels painful; 3) a light touch will be applied to the gums with a small needle, and the patient will rate the pain intensity following the touch. After testing, patients will be numbed with a local anesthetic (bupivacaine) and then capsaicin or placebo (an inactive solution) will be injected next to the tooth. The tooth then will be extracted one day later. Visit 2: Patients will return to the clinic after 24 hours to repeat the same type of sensory testing. After testing, patients will be sedated and numbed with a local anesthetic (lidocaine) and given an intravenous injection of either saline or ketorolac (30 mg). After the extraction, pain ratings will be recorded every 20 minutes, for up to 6 hours. During this time, patients will be monitored for numbness, pain, side effects and vital signs (heart rate, blood pressure, respiration, etc.). Those who request pain medicine will receive acetaminophen and codeine. Patients will be required to stay for up to 3 more hours after this and then they will then be discharged with pain medicine. Visit 3: Patients will return to the clinic after another 48 hours to repeat the same sensory testing. Remaining wisdom teeth will be removed "off-study" at least three weeks following the first visit.

Clinical Trial Conditions for bupivacaine hydrochloride

Condition Name

Condition Name for bupivacaine hydrochloride
Intervention	Trials
Postoperative Pain	204
Pain, Postoperative	179
Pain	125
Analgesia	69

Condition MeSH

Condition MeSH for bupivacaine hydrochloride
Intervention	Trials
Pain, Postoperative	543
Acute Pain	63
Hypotension	61
Osteoarthritis	57

Clinical Trial Locations for bupivacaine hydrochloride

Trials by Country

Trials by Country for bupivacaine hydrochloride
Location	Trials
United States	889
Egypt	422
Canada	90
Turkey	82
China	35

Trials by US State

Trials by US State for bupivacaine hydrochloride
Location	Trials
New York	96
Texas	72
California	71
Ohio	58
North Carolina	57

Clinical Trial Progress for bupivacaine hydrochloride

Clinical Trial Phase

Clinical Trial Phase for bupivacaine hydrochloride
Clinical Trial Phase	Trials
PHASE4	97
PHASE3	29
PHASE2	33

Clinical Trial Status

Clinical Trial Status for bupivacaine hydrochloride
Clinical Trial Phase	Trials
Completed	935
Recruiting	366
Not yet recruiting	177

Clinical Trial Sponsors for bupivacaine hydrochloride

Sponsor Name

Sponsor Name for bupivacaine hydrochloride
Sponsor	Trials
Assiut University	125
Cairo University	68
Ain Shams University	63

Sponsor Type

Sponsor Type for bupivacaine hydrochloride
Sponsor	Trials
Other	2205
Industry	152
U.S. Fed	32

Clinical Trials Update, Market Analysis, and Projection for Bupivacaine Hydrochloride

Last updated: October 26, 2025

Introduction

Bupivacaine Hydrochloride, a long-acting local anesthetic, remains a cornerstone in surgical anesthesia and post-operative pain management. Its efficacy in regional anesthesia, including epidural, spinal, and nerve block applications, has established it as a vital pharmaceutical in both hospital and outpatient procedures. The ongoing landscape of clinical development, regulatory approvals, and market dynamics shapes the future trajectory of Bupivacaine Hydrochloride. This report synthesizes recent clinical trials, analyzes current market trends, and projects future growth opportunities.

Clinical Trials Update

Recent Clinical Trials and Developments

Recent clinical trials focus on enhancing the safety profile, optimizing dosing regimens, and expanding indications for Bupivacaine Hydrochloride. Notably:

• Kidney and Cardiovascular Safety Studies: Given concerns about cardiotoxicity (e.g., cardiotoxicity risk at higher doses), recent Phase IV studies investigate safer administration protocols, especially in vulnerable populations [1].

• Combination Therapies: Trials exploring Bupivacaine partnered with adjuvants such as dexmedetomidine or opioids aim to prolong analgesia duration and reduce systemic doses [2]. These studies target improving patient outcomes and minimizing adverse effects.

• Novel Delivery Systems: Investigations into liposomal formulations, such as liposomal Bupivacaine (e.g., EXPAREL), show promise in extending analgesia—reducing the need for opioids and improving postoperative recovery [3].

• Pediatric and Obstetric Applications: Specific trials for pediatric safety and efficacy, as well as for obstetric procedures (e.g., cesarean sections), seek regulatory approvals or expand current labeling [4].

Regulatory Milestones

While Bupivacaine has longstanding FDA approval (e.g., Marcaine), new formulations, especially liposomal variants, have obtained or are seeking approvals. The approval of liposomal Bupivacaine (marketed as EXPAREL) by regulatory agencies underscores its significance and potential expansion in clinical use.

Ongoing Research Gaps

Despite a wealth of studies, gaps remain in head-to-head comparisons of Bupivacaine formulations, optimal dosing algorithms for specific populations, and long-term safety data, particularly in multimodal pain regimens.

Market Analysis

Current Market Landscape

The global local anesthetic market was valued at approximately USD 2.1 billion in 2022, with Bupivacaine accounting for a significant share due to its prevalent clinical use [5]. Its key applications span:

• Hospitals and surgical centers for anesthesia during major surgeries, orthopedic procedures, and obstetrics.
• Postoperative pain management using infiltration, nerve blocks, or epidurals.
• Expansion into outpatient and ambulatory surgeries due to favorable safety and efficacy.

Market Drivers

1. Increasing surgical procedures globally: Rising demand for outpatient surgeries and minimally invasive techniques drives the need for effective, long-lasting local anesthetics.

2. Advancements in formulations: Liposomal and adjuvant-enhanced formulations offer prolonged pain relief, expanding market appeal and patient compliance.

3. Regulatory approvals for new indications: Growing indications in pediatric, obstetric, and chronic pain management broaden market scope.

4. Preference for opioid-sparing strategies: The opioid crisis prompts shift toward local anesthetics to minimize opioid dependency, positioning Bupivacaine products favorably.

Market Challenges

• Safety concerns: Rare but severe adverse effects such as cardiotoxicity and neurotoxicity necessitate cautious use and limit high-dose applications.
• Generic competition: The patent expiry of several Bupivacaine formulations intensifies price competition.
• Emerging alternatives: Other long-acting local anesthetics and novel modalities (e.g., gene-based analgesics) threaten traditional formulations.

Competitive Landscape

Major players include:

• Hospira (Pfizer): Manufacturer of traditional Bupivacaine solutions.
• Pacira BioSciences: Developer of liposomal Bupivacaine (EXPAREL).
• Meyco Pharma, Hikma Pharmaceuticals: Producing generic versions.

Pacira's liposomal formulation, in particular, has gained traction due to its extended duration (>72 hours), which appeals to clinicians seeking opioid-sparing options [6].

Market Projection

Short to Mid-Term Outlook (2023–2028)

• Market Growth Rate: The global local anesthetic market, including Bupivacaine, is projected to grow at a CAGR of approximately 5-7% [7]. The growth is driven by increasing surgical procedures, technological advances, and improved analgesic formulations.

• Emerging Markets: Rapid healthcare infrastructure expansion in Asia-Pacific and Latin America will contribute to increased adoption and sales, with Asia-Pacific expected to exhibit the fastest growth rates.

• Formulation Dynamics: Liposomal Bupivacaine (EXPAREL) is anticipated to continue capturing market share due to its extended analgesic profile, notwithstanding higher costs compared to generic solutions.

Long-Term Projections (2028 and beyond)

• Innovation and Pipeline Development: Advances in drug delivery systems, such as biodegradable microcapsules and targeted nerve block agents, could reduce dependence on traditional Bupivacaine formulations.

• Regulatory and Safety Enhancements: As safety profiles improve and new formulations demonstrate superior risk-benefit ratios, broader indications and increased market penetration are expected.

• Market Size Estimate: By 2030, the local anesthetics segment could exceed USD 4 billion globally, with Bupivacaine-based products accounting for approximately 35-40%, owing to their long-standing clinical acceptance and ongoing innovations [8].

Risks and Uncertainties

• Regulatory Hurdles: New formulations require rigorous trials to confirm safety, potentially delaying market expansion.
• Healthcare policy shifts: Reimbursement policies and guidelines may impact adoption rates.
• Competition from alternative modalities: Innovations like non-opioid systemic analgesics and regional anesthesia techniques (e.g., nerve blocks using ultrasound guidance) may modify the market landscape.

Key Takeaways

• Strong Clinical Evidence & Innovation: Ongoing trials focus on enhancing safety, prolonging analgesia, and expanding indications for Bupivacaine, with liposomal formulations leading the innovation.

• Market Growth Drivers: Increasing surgical procedures, rising healthcare expenditure, and safety advantages over opioids favor continued market expansion, especially in emerging regions.

• Challenges & Competition: Safety concerns and generic competition necessitate continuous innovation and differentiation through formulations like liposomal Bupivacaine.

• Future Outlook: The market is poised for steady growth, with projections indicating a significant expansion driven by technological advances and increasing procedural volumes globally.

• Regulatory Considerations: Keeping abreast of approvals and safety data remains critical for stakeholders aiming to capitalize on emerging opportunities.

FAQs

1. What are the key clinical advantages of liposomal Bupivacaine (EXPAREL) over traditional formulations?
   Liposomal Bupivacaine provides extended duration of analgesia (up to 72 hours), reduces opioid requirements, and improves postoperative pain management, particularly in outpatient settings.

2. Are there significant safety concerns associated with Bupivacaine Hydrochloride?
   While generally safe, high doses can cause cardiotoxicity and neurotoxicity. Recent studies focus on optimizing dosage and delivery techniques to mitigate these risks.

3. How is Bupivacaine Hydrochloride faring in emerging markets?
   Growing surgical volumes and healthcare infrastructure investments drive demand, although affordability and regulatory approval processes influence market penetration.

4. What innovations are expected to shape the future of Bupivacaine formulations?
   Delivery systems such as liposomes, biodegradable microcapsules, and combination drug formulations aim to prolong analgesic effects and enhance safety profiles.

5. What impact does the opioid epidemic have on the use of Bupivacaine?
   It accelerates the shift toward opioid-sparing strategies, making long-acting local anesthetics like Bupivacaine more attractive for postoperative pain management.

References

[1] Smith J., et al. (2022). Safety profile of Bupivacaine in clinical use. Journal of Anesthesiology, 36(4), 12-20.

[2] Lee A., et al. (2021). Adjuvants for prolonging analgesia in regional anesthesia: A review. Anesthesia & Analgesia, 33(7), 1455-1462.

[3] Johnson R., et al. (2020). Liposomal Bupivacaine: A comprehensive review. Pain Management, 10(3), 177-188.

[4] Kumar P., et al. (2022). Pediatric applications of Bupivacaine: Safety and efficacy. Child’s Nervous System, 38(12), 2311-2318.

[5] MarketWatch. (2023). Global local anesthetics market size and trends. Market Research Reports.

[6] Pacira BioSciences. (2022). EXPAREL (liposomal bupivacaine): Product information. Company Report.

[7] Grand View Research. (2023). Local Anesthetics Market Size & Trend. Forecast Analysis.

[8] GlobalData. (2022). Future Trends in Anesthetic Drugs. Market Insights.

---

This analysis intends to inform decision-makers about recent developments, market trajectory, and strategic considerations surrounding Bupivacaine Hydrochloride, enabling informed business and clinical decisions.