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
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.
New Formulation	NCT02947178 ↗	Hip Arthroscopy Pain Control Randomized Control Trial (RCT)	Completed	Walter Reed National Military Medical Center	Phase 4	2016-03-01	Femoroacetabular impingement is a pathologic process within the hip joint that results from a mechanical discord between the femoral head and neck and the acetabulum that results in chronic hip pain, hip labral tears and early progression of osteoarthritis of the hip.1, 2 Historically an open surgical hip dislocation was performed to treat patients with this condition, however with recent advances in arthroscopy, patients more commonly now undergo arthroscopic hip surgery. From a pain management standpoint, previous attempts to provide peri-operative analgesia included intraarticular or portal analgesic injections. More recently, regional anesthesia techniques are being employed to provide more reliable and longer lasting post-operative pain control.3, 4 Currently, there are several local anesthetics available for regional anesthesia. However, they only provide an average of 12-18 hours of post-operative pain control following a single injection.5 Bupivacaine is a local anesthetic that has been used for many years by multiple routes to control post-operative pain. A new formulation of the medication prolongs the release of the active ingredient after a single injection and has been shown to result in up to 72 hours of post-operative analgesia.6, 7 To the investigator's knowledge, there has not been any studies in the literature comparing a historical control local anesthetic to this new formulation of liposomal bupivacaine via a fascial iliaca regional soft tissue infiltration blockade to provide post operative pain control following hip arthroscopy.
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.

All Clinical Trials for BUPIVACAINE HYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00050362 ↗	Rofecoxib and Bupivacaine to Prevent Pain After Third Molar (Wisdom Tooth) Extraction	Completed	National Institute of Dental and Craniofacial Research (NIDCR)	Phase 2	2002-12-01	This study will evaluate the ability of the drugs rofecoxib and bupivacaine to prevent pain following third molar (wisdom tooth) extraction. Rofecoxib is approved to treat pain of arthritis and menstrual cramps. Bupivacaine is a local anesthetic similar to lidocaine, but longer acting. Healthy normal volunteers between 16 and 35 years of age who are in general good health and require extraction of their two lower wisdom teeth may be eligible for this study. Participants will have their two lower wisdom teeth extracted, and a biopsy (removal of a small piece of tissue) will be taken from the inside of the cheek around the area behind one of the extraction sites. Ninety minutes before surgery, patients will take a dose of either rofecoxib, or a placebo (a pill with no active ingredient) by mouth. Just before surgery, they will receive an injection of either lidocaine or bupivacaine to numb the mouth and a sedative called midazolam (Versed® (Registered Trademark)) through an arm vein to cause drowsiness. After surgery, a small piece of tubing will be placed into one of the two extraction sites. Samples will be collected from the tubing to measure chemicals involved in pain and inflammation. Patients will remain in the clinic for up to 4 hours after surgery to monitor pain and drug side effects while the anesthetic wears off. During this time, they will complete pain questionnaires every 20 minutes. (Patients whose pain is unrelieved an hour after surgery may request and receive acetaminophen (Tylenol) and codeine.) The tubing then will be removed and they will be discharged with pain medicines (Tylenol, codeine and the study drug) and forms to record pain ratings. They will be given detailed instructions on how and when to take the medicines and how to record information in the pain diary. Patients will return to the clinic 48 hours after surgery with the pain diary and pain relievers. At this visit, another biopsy will be taken under local anesthetic (lidocaine).
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.
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.
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.

Clinical Trial Conditions for BUPIVACAINE HYDROCHLORIDE

Condition Name

Condition Name for BUPIVACAINE HYDROCHLORIDE
Intervention	Trials
Postoperative Pain	178
Pain, Postoperative	169
Pain	120
Analgesia	57

Condition MeSH

Condition MeSH for BUPIVACAINE HYDROCHLORIDE
Intervention	Trials
Pain, Postoperative	459
Osteoarthritis	56
Acute Pain	56
Hypotension	53

Clinical Trial Locations for BUPIVACAINE HYDROCHLORIDE

Trials by Country

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Trials by Country for BUPIVACAINE HYDROCHLORIDE
Location	Trials
United States	832
Egypt	313
Canada	82
Turkey	82
Denmark	29

Trials by US State

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−

Trials by US State for BUPIVACAINE HYDROCHLORIDE
Location	Trials
New York	93
California	67
Texas	64
Ohio	56
Pennsylvania	52

Clinical Trial Progress for BUPIVACAINE HYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for BUPIVACAINE HYDROCHLORIDE
Clinical Trial Phase	Trials
Phase 4	640
Phase 3	140
Phase 2/Phase 3	70

Clinical Trial Status

Clinical Trial Status for BUPIVACAINE HYDROCHLORIDE
Clinical Trial Phase	Trials
Completed	837
Recruiting	272
Not yet recruiting	177

Clinical Trial Sponsors for BUPIVACAINE HYDROCHLORIDE

Sponsor Name

Sponsor Name for BUPIVACAINE HYDROCHLORIDE
Sponsor	Trials
Assiut University	99
Pacira Pharmaceuticals, Inc	59
Cairo University	50

Sponsor Type

Sponsor Type for BUPIVACAINE HYDROCHLORIDE
Sponsor	Trials
Other	1912
Industry	144
U.S. Fed	32

Bupivacaine Hydrochloride: Clinical Trials, Market Analysis, and Projections

Introduction

Bupivacaine hydrochloride is a widely used local anesthetic belonging to the amide class, known for its long-lasting analgesic effects. It is commonly administered via injection for pain management during surgical procedures, childbirth, and postoperative care. Here, we will delve into recent clinical trials, market analysis, and future projections for bupivacaine hydrochloride.

Clinical Trials: Efficacy and Safety

Liposomal Bupivacaine vs. Bupivacaine Hydrochloride

A significant clinical trial published in JAMA Surgery compared the efficacy of liposomal bupivacaine with bupivacaine hydrochloride alone in patients undergoing primary unilateral knee replacement. This multicenter, patient-blinded, pragmatic, randomized clinical trial involved 533 participants and found that liposomal bupivacaine did not improve postoperative recovery or pain compared to bupivacaine hydrochloride alone[1].

HTX-011 vs. Bupivacaine HCl

The EPOCH 1 study, a phase III randomized, double-blind, placebo-controlled trial, compared HTX-011 (a combination of bupivacaine and meloxicam) with immediate-release bupivacaine HCl and saline placebo in patients undergoing bunionectomy. The study demonstrated that HTX-011 provided superior and sustained pain reduction through 72 hours postoperatively, significantly reduced opioid consumption, and resulted in more opioid-free subjects compared to bupivacaine HCl[4].

Market Analysis

Global Market Size and Growth

The global market for bupivacaine hydrochloride was valued at USD 265.06 million in 2023 and is projected to reach USD 432.83 million by 2032, growing at a CAGR of 5.6% from 2024 to 2032[2].

Regional Market Dynamics

North America dominates the bupivacaine hydrochloride market due to high healthcare expenditure and advanced healthcare infrastructure. Europe follows closely, driven by increasing awareness of pain management and supportive government initiatives. The Asia Pacific region is witnessing significant growth due to rising healthcare investments, improving healthcare infrastructure, and increasing adoption of advanced pain management techniques[2].

Key Players and Market Trends

The market is influenced by several key players, including Pfizer, Fresenius Kabi, Hikma Pharmaceuticals, and others. The increasing demand for regional anesthesia, technological advancements in drug delivery systems, and the expanding geriatric population are driving market growth. Local pharmaceutical companies in the Asia Pacific region are focusing on research and development to develop novel formulations and drug delivery systems, further boosting the market[2][5].

Market Projections

Forecasted Market Size

By 2030, the global market for bupivacaine hydrochloride is forecasted to reach USD 361.9 million, growing at a CAGR of 5.4% from 2024 to 2030[5].

Growth Factors

The market is expected to grow due to several factors:

• Increasing Surgical Procedures: The rise in surgical procedures globally is driving the demand for effective pain management solutions.
• Chronic Pain Conditions: The increasing prevalence of chronic pain conditions necessitates the use of long-lasting local anesthetics like bupivacaine hydrochloride.
• Technological Advancements: Improvements in drug delivery systems are enhancing the efficacy and safety of bupivacaine hydrochloride administration[2][5].

Safety and Toxicology

FDA Guidelines

The FDA emphasizes the importance of toxicology studies to characterize the safety profile of bupivacaine. These studies should aim to identify the NOAEL (No Observed Adverse Effect Level), characterize local and systemic target organ toxicity, and provide adequate safety margins for the maximum recommended human dose. The studies may be conducted with the drug substance instead of the final product, especially if achieving adequate exposures in animal models is challenging[3].

Conclusion

Bupivacaine hydrochloride remains a crucial component in pain management, with ongoing clinical trials and market analyses providing valuable insights into its efficacy and market dynamics. While recent trials have shown mixed results regarding the superiority of certain formulations, the overall market is poised for steady growth driven by increasing demand for effective pain management solutions and advancements in drug delivery technologies.

Key Takeaways

• Clinical Efficacy: Recent trials indicate that while bupivacaine hydrochloride is effective, some formulations like HTX-011 may offer superior pain reduction and reduced opioid consumption.
• Market Growth: The global market for bupivacaine hydrochloride is expected to grow at a CAGR of 5.6% from 2024 to 2032.
• Regional Dynamics: North America and Europe are current leaders, but the Asia Pacific region is emerging as a significant market due to improving healthcare infrastructure and increasing adoption of advanced pain management techniques.
• Safety and Toxicology: FDA guidelines emphasize the need for comprehensive toxicology studies to ensure the safety of bupivacaine hydrochloride.

FAQs

Q: What are the primary uses of bupivacaine hydrochloride?

A: Bupivacaine hydrochloride is primarily used for pain management during surgical procedures, childbirth, and postoperative care.

Q: How does the market for bupivacaine hydrochloride project to grow in the coming years?

A: The market is projected to grow at a CAGR of 5.6% from 2024 to 2032, reaching USD 432.83 million by 2032.

Q: Which regions are driving the growth of the bupivacaine hydrochloride market?

A: North America and Europe are current leaders, but the Asia Pacific region is experiencing significant growth due to rising healthcare investments and improving infrastructure.

Q: What are the key factors driving the growth of the bupivacaine hydrochloride market?

A: The growth is driven by increasing surgical procedures, the prevalence of chronic pain conditions, and technological advancements in drug delivery systems.

Q: What are the safety considerations for bupivacaine hydrochloride as per FDA guidelines?

A: The FDA emphasizes the need for toxicology studies to characterize the safety profile, including identifying NOAEL, local and systemic toxicity, and ensuring adequate safety margins for the maximum recommended human dose.

Sources

1. JAMA Surgery: Efficacy of Liposomal Bupivacaine and Bupivacaine Hydrochloride...
2. Introspectivemarketresearch.com: Bupivacaine HCl Market - Global Size, Share & Industry Trends
3. FDA: 209511Orig1s000 - accessdata.fda.gov
4. BMJ: Phase III results from the randomized EPOCH 1 study
5. Valuates Reports: Bupivacaine Hydrochloride - Market Size - Valuates Reports