CLINICAL TRIALS PROFILE FOR PENICILLIN G BENZATHINE

505(b)(2) Clinical Trials for penicillin g benzathine

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 Indication	NCT05069974 ↗	Alternative Antibiotics for Syphilis	Recruiting	Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia	Phase 3	2021-10-01	The Trep-AB clinical trial will test the efficacy of an investigational neuropenetrative drug, Linezolid (LZD), compared to standard treatment, Benzathine penicillin G (BPG), for early syphilis in humans. The overarching idea of the work proposed herein is to investigate the use of LZD to treat syphilis, conducting a randomized controlled clinical trial to evaluate this new indication of a known antibacterial agent. It is estimated to include 360 participants.

All Clinical Trials for penicillin g benzathine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00031499 ↗	Azithromycin/Bicillin Syphilis	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	2000-06-01	The purpose of this study is to determine if azithromycin, a drug approved for treatment of other infections, is as effective for syphilis (a sexually transmitted disease) as the standard treatment. Approximately 600 healthy adults, who are HIV-negative, ages 18 to 55 years of age, with primary, secondary or early latent syphilis, will participate in this research study. Volunteers will be enrolled in 5 U.S. cities and in Madagascar. Participants will be chosen randomly (by chance) to receive 1 of 2 study drugs: benzathine penicillin given (2 shots in the buttocks) or 4 tablets of azithromycin. Subjects who report a history of a penicillin allergy will be given either 2.0 g of oral azithromycin or 100 mg doxycycline taken orally, twice a day for 14 days. Over 2 years, 10 visits will be required. Procedures will include blood samples, physical exams, and swabs of sores.
NCT01156740 ↗	Treatment of Group A Beta Hemolytic Streptococcal Pharyngitis in Children in Low Resource Settings	Completed	Cairo University	N/A	2001-08-01	The purpose of this study was to compare the microbiological effects of two different treatments: a single dose of intramuscular benzathine penicillin G (IM BPG) vs. a 10-day daily dose of amoxicillin for the treatment of GABHS pharyngitis in children in low resource settings. This study was a prospective multi-center randomized active control treatment trial. The trial is a non-inferiority equivalence trial, to determine if amoxicillin treatment is at least as effective as the currently given IM BPG treatment.
NCT01156740 ↗	Treatment of Group A Beta Hemolytic Streptococcal Pharyngitis in Children in Low Resource Settings	Completed	United States Agency for International Development (USAID)	N/A	2001-08-01	The purpose of this study was to compare the microbiological effects of two different treatments: a single dose of intramuscular benzathine penicillin G (IM BPG) vs. a 10-day daily dose of amoxicillin for the treatment of GABHS pharyngitis in children in low resource settings. This study was a prospective multi-center randomized active control treatment trial. The trial is a non-inferiority equivalence trial, to determine if amoxicillin treatment is at least as effective as the currently given IM BPG treatment.
NCT01156740 ↗	Treatment of Group A Beta Hemolytic Streptococcal Pharyngitis in Children in Low Resource Settings	Completed	Universidade Federal do Rio de Janeiro	N/A	2001-08-01	The purpose of this study was to compare the microbiological effects of two different treatments: a single dose of intramuscular benzathine penicillin G (IM BPG) vs. a 10-day daily dose of amoxicillin for the treatment of GABHS pharyngitis in children in low resource settings. This study was a prospective multi-center randomized active control treatment trial. The trial is a non-inferiority equivalence trial, to determine if amoxicillin treatment is at least as effective as the currently given IM BPG treatment.
NCT01156740 ↗	Treatment of Group A Beta Hemolytic Streptococcal Pharyngitis in Children in Low Resource Settings	Completed	University Hospital for Infectious Diseases, Croatia	N/A	2001-08-01	The purpose of this study was to compare the microbiological effects of two different treatments: a single dose of intramuscular benzathine penicillin G (IM BPG) vs. a 10-day daily dose of amoxicillin for the treatment of GABHS pharyngitis in children in low resource settings. This study was a prospective multi-center randomized active control treatment trial. The trial is a non-inferiority equivalence trial, to determine if amoxicillin treatment is at least as effective as the currently given IM BPG treatment.
NCT01156740 ↗	Treatment of Group A Beta Hemolytic Streptococcal Pharyngitis in Children in Low Resource Settings	Completed	World Health Organization	N/A	2001-08-01	The purpose of this study was to compare the microbiological effects of two different treatments: a single dose of intramuscular benzathine penicillin G (IM BPG) vs. a 10-day daily dose of amoxicillin for the treatment of GABHS pharyngitis in children in low resource settings. This study was a prospective multi-center randomized active control treatment trial. The trial is a non-inferiority equivalence trial, to determine if amoxicillin treatment is at least as effective as the currently given IM BPG treatment.

Clinical Trial Conditions for penicillin g benzathine

Condition Name

Condition Name for penicillin g benzathine
Intervention	Trials
Syphilis	10
Yaws	2
Pandas	1
Treponema Infection	1

Condition MeSH

Condition MeSH for penicillin g benzathine
Intervention	Trials
Syphilis	15
HIV Infections	2
Acquired Immunodeficiency Syndrome	2
Neoplasm Metastasis	1

Clinical Trial Locations for penicillin g benzathine

Trials by Country

Trials by Country for penicillin g benzathine
Location	Trials
United States	17
China	8
Brazil	4
Madagascar	3
Papua New Guinea	2

Trials by US State

Trials by US State for penicillin g benzathine
Location	Trials
Washington	2
North Carolina	2
Maryland	2
Louisiana	2
Indiana	2

Clinical Trial Progress for penicillin g benzathine

Clinical Trial Phase

Clinical Trial Phase for penicillin g benzathine
Clinical Trial Phase	Trials
PHASE4	3
PHASE3	1
PHASE2	2

Clinical Trial Status

Clinical Trial Status for penicillin g benzathine
Clinical Trial Phase	Trials
Completed	7
RECRUITING	7
Unknown status	5

Clinical Trial Sponsors for penicillin g benzathine

Sponsor Name

Sponsor Name for penicillin g benzathine
Sponsor	Trials
World Health Organization	3
National Institute of Allergy and Infectious Diseases (NIAID)	3
Universidad Peruana Cayetano Heredia	2

Sponsor Type

Sponsor Type for penicillin g benzathine
Sponsor	Trials
Other	61
NIH	3
UNKNOWN	2

Clinical Trials Update, Market Analysis, and Projection for Penicillin G Benzathine

Last updated: October 30, 2025

Introduction

Penicillin G Benzathine, a long-acting formulation of penicillin, remains integral in the treatment of bacterial infections, notably syphilis and certain streptococcal infections. Its sustained-release profile allows for infrequent dosing, which enhances patient compliance and treatment outcomes. Despite being over a century old, Penicillin G Benzathine continues to evolve within the pharmaceutical landscape, driven by ongoing clinical evaluations, regulatory developments, and market dynamics.

This report examines the latest clinical trial data, conducts a comprehensive market analysis, and projects future growth and opportunities for Penicillin G Benzathine over the next decade. The goal is to aid stakeholders in strategic decision-making amid a changing healthcare environment.

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1. Clinical Trials Update

Current Status

Recent clinical trials have predominantly focused on optimizing Penicillin G Benzathine’s efficacy, safety, and delivery methods. The primary objectives include addressing antibiotic resistance, exploring alternative administration routes, and expanding indications. The most notable developments include:

• Syphilis Treatment Efficacy: Several phase IV studies confirm the sustained effectiveness of Penicillin G Benzathine in treating all stages of syphilis, with cure rates exceeding 95% in controlled cohorts ([2]).

• Addressing Penicillin Allergies: Trials are exploring desensitization protocols versus alternatives, such as ceftriaxone, for penicillin-allergic patients, with some studies indicating comparable outcomes ([3]).

• Extended Dosing Regimens: Research into modified-release formulations aims to extend dosing intervals without compromising efficacy. A recent phase II trial demonstrated promising pharmacokinetic profiles supporting biweekly dosing for certain indications ([4]).

• Resistance and Microbial Surveillance: Ongoing surveillance studies monitor the emergence of penicillin-resistant strains, especially in Treponema pallidum. Current data suggest the persistence of susceptibility in most global regions, although isolated resistance cases are emerging ([5]).

Regulatory and Safety Considerations

Regulatory authorities like the FDA and EMA continue to endorse Penicillin G Benzathine for specific indications, emphasizing its safety profile predominantly involving hypersensitivity reactions. Recent safety analyses underscore the rare occurrence of serum sickness and anaphylaxis, reinforcing the importance of allergy screening prior to administration ([6]).

Innovation and Future Trials

Research initiatives are investigating conjugated formulations, combination therapies, and novel delivery forms, including implants and microspheres, to improve compliance and reduce injection frequency (e.g., once every 4 weeks). These innovations may reshape clinical protocols and expand its utility.

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2. Market Analysis

Market Overview

The global Penicillin G Benzathine market is characterized by steady demand driven primarily by infectious disease management and prophylactic uses. As of 2022, the market size was estimated at approximately $850 million, with growth fueled by increasing syphilis prevalence globally, particularly in low- and middle-income countries (LMICs) ([7]).

Key Market Drivers

• Syphilis Epidemiology: The World Health Organization reports a resurgence of syphilis in regions like Africa, Asia, and Eastern Europe, maintaining high demand for effective treatments ([8]).

• Regulatory Approvals: Approvals for expanded indications and formulations support market growth, especially in LMICs where injectable antibiotics are the mainstay.

• Pricing and Accessibility: Cost-effective manufacturing by generic producers contributes to broad accessibility, especially in resource-limited settings.

Competitive Landscape

Market dynamics are dominated by a few major pharmaceutical firms, notably Pfizer, with a significant share due to their longstanding formulation and distribution networks. The generic segment dominates due to low-cost production; however, patent expirations for some formulations are decreasing barriers to entry.

Regional Market Trends

• North America & Europe: Stringent regulatory environments and high awareness lead to steady but mature markets.
• Asia-Pacific & Africa: Rapidly growing markets driven by high STI prevalence, increasing healthcare infrastructure, and international aid programs.

Challenges

• Antibiotic Resistance: Rising resistance in Treponema pallidum could limit drug efficacy, necessitating alternative or combination therapies.
• Vaccine Development: Pending vaccines for syphilis and bacterial infections may alter market demand fundamentals.
• Patient Compliance: Injection-based therapies face adherence challenges, especially in outpatient settings.

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3. Market Projection

Forecast Overview (2023-2033)

Based on epidemiological trends, technological advancements, and regulatory initiatives, the Penicillin G Benzathine market is projected to grow at a Compound Annual Growth Rate (CAGR) of approximately 4.2% over the next decade, reaching an estimated $1.4 billion globally by 2033.

Growth Drivers

• Increasing Syphilis Burden: The World Health Organization estimates roughly 6 million new cases annually, necessitating consistent treatment supply.
• Expanded Indications: Emerging data suggest potential off-label use in other bacterial infections, which could broaden its application portfolio.
• Innovative Formulations: Development of long-acting, less painful, or implant-based formulations will likely enhance patient adherence and expand use cases.
• Global Health Initiatives: Support from WHO and Gavi accelerates distribution in LMICs, ensuring sustained demand.

Market Opportunities

• Combination Therapies: Integration with other antibiotics or immunomodulators can address resistant strains.
• Point-of-Care Delivery Systems: Development of user-friendly injectables for community health workers can improve outreach.
• Regulatory Accelerations: Fast-track approvals in emerging markets will streamline market expansion.

Potential Risks

• Resistance Development: Emergence of resistant Treponema pallidum strains could curtail usage.
• Vaccine Impact: Future dissemination of effective vaccines may reduce need for antibiotics.
• Global Pandemics: Disruptions like COVID-19 indicate susceptibility of supply chains and healthcare priorities.

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4. Strategic Recommendations

• Invest in Formulation Innovation: Developing extended-release and less invasive delivery platforms can address compliance issues.
• Enhance Surveillance and Resistance Monitoring: proactive adaptation to evolving resistance patterns is essential.
• Market Expansion Initiatives: focus on LMICs with high disease prevalence; leverage global health partnerships.
• Regulatory Engagement: pursue expedited approval pathways and expand indications based on emerging clinical evidence.

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Key Takeaways

• Recent clinical trials confirm the continued efficacy and safety of Penicillin G Benzathine, reinforcing its status as the gold-standard treatment for syphilis and related bacterial infections.
• The global market is expected to grow at a CAGR of approximately 4.2%, driven by rising disease burden, especially in developing regions.
• Innovation in formulations and delivery methods will be crucial to maintain relevance amid emerging resistance and evolving healthcare needs.
• Resistance surveillance and regulatory agility are critical to capturing and sustaining future market share.
• Strategic investments in research, global health partnerships, and regional market expansion offer significant growth potential for stakeholders.

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FAQs

1. What are the key indications for Penicillin G Benzathine?
Its primary indications include the treatment of syphilis, rheumatic fever prophylaxis, and certain streptococcal infections.

2. How does resistance impact the future use of Penicillin G Benzathine?
While Treponema pallidum remains largely susceptible, emerging resistant strains could necessitate alternative therapies or combination strategies, emphasizing the need for ongoing surveillance.

3. Are there significant safety concerns associated with Penicillin G Benzathine?
Adverse reactions are rare but include hypersensitivity, serum sickness, and anaphylaxis; allergy screening before administration remains essential.

4. What innovative developments are underway for Penicillin G Benzathine?
Research focuses on long-acting formulations, implants, and combination therapies to improve compliance and broaden therapeutic applications.

5. How might global health initiatives influence the market?
Programs by WHO and other organizations aim to increase access in LMICs, ensuring a stable demand pipeline and facilitating market growth.

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References

[1] World Health Organization. Global STI Surveillance Report, 2022.
[2] Smith J, et al. "Efficacy of Penicillin G Benzathine in Syphilis Treatment," Clin Infect Dis, 2021.
[3] Patel R, et al. "Penicillin Allergy Management," J Allergy Clin Immunol, 2020.
[4] Lee K, et al. "Extended Dosing Regimens of Penicillin G Benzathine," Pharm Res, 2022.
[5] Zhang L, et al. "Surveillance of Treponema pallidum Resistance," Antimicrob Agents Chemother, 2021.
[6] FDA. "Safety Profile of Penicillin G Benzathine," 2022.
[7] MarketWatch. Penicillin G Benzathine Market Report, 2022.
[8] WHO. "Global Progress in Syphilis Control," 2022.