CLINICAL TRIALS PROFILE FOR SULFAMETHOXAZOLE AND TRIMETHOPRIM

505(b)(2) Clinical Trials for SULFAMETHOXAZOLE AND TRIMETHOPRIM

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 Combination	NCT03431168 ↗	A Novel Regimen to Prevent Malaria and STI in Pregnant Women With HIV	Active, not recruiting	University of Alabama at Birmingham	Phase 2	2018-03-07	More than 3 billion people worldwide are at risk of acquiring malaria and pregnant women living with HIV in Africa are at particular risk. An effective prophylaxis regimen capable of preventing malaria and other common perinatal infections would have great potential to improve adverse birth outcomes. The purpose of this randomized controlled trial is to evaluate a new combination prophylaxis regimen in pregnant women with HIV in Cameroon to determine its efficacy and safety.
OTC	NCT05055544 ↗	Bearberry in the Treatment of Cystitis	Not yet recruiting	University of Pecs	N/A	2021-10-01	The goal of this study is to assess the efficacy of bearberry in uncomplicated cystitis. Uncomplicated cystitis is a disease related to the infection of the urinary bladder. Typical symptoms are dysuria, urinary urgency, and frequent voiding of small volumes. Urinary tract infections are frequent in women, usually treated with antibiotics, since the disease is usually caused by bacteria. Fosfomycin is a frequently used antibiotic for the treatment of uncomplicated cystitis. This medicine is typically prescribed by MDs. However, since uncomplicated cystitis is quite frequent, not all patients visit the doctor when experiencing the symptoms of this disease. The use of over-the-counter products (medicines and food supplements) to alleviate the symptoms is common. One of the most frequently used medicinal plants for this purpose is bearberry. Bearberry is a medicinal plant traditionally used for the treatment of cystitis. Its use is accepted by the European Medicine Agency as traditional herbal medicinal product for relief of symptoms of mild recurrent lower urinary tract infections such as burning sensation during urination and/or frequent urination in women. Although the experience gained during the traditional use and the laboratory experiments support the supposed beneficial effect of bearberry, its clinical efficacy has not been confirmed in well-designed clinical trials in comparison with standard antibiotic therapy. In this study, the efficacy of bearberry will be assessed in comparison with fosfomycin. Premenopausal women experiencing the symptoms of uncomplicated cystitis will be randomly divided into two groups. Since it will be a double-blind trial, neither the participants nor the experimenters will know who is receiving a particular treatment. In group A, patients will receive a single dose of fosfomycin powder dissolved in water and 2 placebo tablets three times a day for 7 days. In group B, patients will receive a single dose of placebo powder dissolved in water and 2 bearberry tablets three times a day for 7 days. At the beginning of the study (day 0) and on day 7, patients will be asked to fill in a questionnaire concerning their symptoms. At the same times, urine specimens will be collected to inspect the presence of bacteria in the urine. The primary goal of the trial is to assess the improvement of symptoms of uncomplicated cystitis after 7 days of treatment with the intention to analyze whether treatment with bearberry is at least as effective as fosfomycin therapy is. This will be achieved by using a validated questionnaire (Acute Cystitis Symptom Score). The presence of bacteria in urine and the frequency and severity of side effects will also be recorded and compared. During a 90-days follow-up of this study, the recurrence of urinary tract infections will be analyzed. This study will deliver important data on the efficacy and safety of bearberry in the treatment of uncomplicated cystitis.

All Clinical Trials for SULFAMETHOXAZOLE AND TRIMETHOPRIM

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000640 ↗	A Phase III Comparative Study of Dapsone / Trimethoprim and Clindamycin / Primaquine Versus Sulfamethoxazole / Trimethoprim in the Treatment of Mild-to-Moderate PCP in Patients With AIDS	Completed	Glaxo Wellcome	Phase 3	1969-12-31	To evaluate the effectiveness of two oral treatments for mild to moderate Pneumocystis carinii pneumonia (PCP): dapsone/trimethoprim or clindamycin/primaquine as compared to a standard treatment program of sulfamethoxazole/trimethoprim (SMX/TMP) to assess the tolerance of these two alternative treatments as compared to the standard treatment of SMX/TMP. Per 09/09/92 amendment, to assess the efficacy and tolerance of these two alternative treatments in patients who are intolerant to SMX/TMP. The type of treatment being studied has the advantages of wide applicability throughout the world (including developing countries) and low cost. An oral treatment is more accessible to patients than drugs given by injection or by inhalation.
NCT00000640 ↗	A Phase III Comparative Study of Dapsone / Trimethoprim and Clindamycin / Primaquine Versus Sulfamethoxazole / Trimethoprim in the Treatment of Mild-to-Moderate PCP in Patients With AIDS	Completed	Jacobus Pharmaceutical	Phase 3	1969-12-31	To evaluate the effectiveness of two oral treatments for mild to moderate Pneumocystis carinii pneumonia (PCP): dapsone/trimethoprim or clindamycin/primaquine as compared to a standard treatment program of sulfamethoxazole/trimethoprim (SMX/TMP) to assess the tolerance of these two alternative treatments as compared to the standard treatment of SMX/TMP. Per 09/09/92 amendment, to assess the efficacy and tolerance of these two alternative treatments in patients who are intolerant to SMX/TMP. The type of treatment being studied has the advantages of wide applicability throughout the world (including developing countries) and low cost. An oral treatment is more accessible to patients than drugs given by injection or by inhalation.
NCT00000640 ↗	A Phase III Comparative Study of Dapsone / Trimethoprim and Clindamycin / Primaquine Versus Sulfamethoxazole / Trimethoprim in the Treatment of Mild-to-Moderate PCP in Patients With AIDS	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To evaluate the effectiveness of two oral treatments for mild to moderate Pneumocystis carinii pneumonia (PCP): dapsone/trimethoprim or clindamycin/primaquine as compared to a standard treatment program of sulfamethoxazole/trimethoprim (SMX/TMP) to assess the tolerance of these two alternative treatments as compared to the standard treatment of SMX/TMP. Per 09/09/92 amendment, to assess the efficacy and tolerance of these two alternative treatments in patients who are intolerant to SMX/TMP. The type of treatment being studied has the advantages of wide applicability throughout the world (including developing countries) and low cost. An oral treatment is more accessible to patients than drugs given by injection or by inhalation.
NCT00000655 ↗	A Randomized, Double-Blind Study of 566C80 Versus Septra (Sulfamethoxazole/Trimethoprim) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients	Completed	Glaxo Wellcome	Phase 2	1969-12-31	To evaluate the effectiveness of atovaquone (566C80) compared to a standard antipneumocystis agent, (SMX/TMP), for the treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in AIDS patients. To compare the safety of short-term (21 days) treatment with 566C80 and SMX/TMP in AIDS patients with an acute episode of PCP. Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.
NCT00000655 ↗	A Randomized, Double-Blind Study of 566C80 Versus Septra (Sulfamethoxazole/Trimethoprim) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To evaluate the effectiveness of atovaquone (566C80) compared to a standard antipneumocystis agent, (SMX/TMP), for the treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in AIDS patients. To compare the safety of short-term (21 days) treatment with 566C80 and SMX/TMP in AIDS patients with an acute episode of PCP. Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.
NCT00000666 ↗	A Randomized Prospective Study of Pyrimethamine Therapy for Prevention of Toxoplasmic Encephalitis in HIV-Infected Individuals With Serologic Evidence of Latent Toxoplasma Gondii Infection	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To evaluate pyrimethamine as a prophylactic agent against toxoplasmic encephalitis in individuals who are coinfected with HIV and latent Toxoplasma gondii. Toxoplasmic encephalitis is a major cause of illness and death in AIDS patients. Standard treatment for toxoplasmic encephalitis is to combine pyrimethamine and sulfadiazine. Continuous treatment is necessary to prevent recurrence of the disease, but constant use of pyrimethamine/sulfadiazine is associated with toxicity. Clindamycin has been shown to be effective in treatment of toxoplasmic encephalitis in animal studies. This study evaluates pyrimethamine as a preventive treatment against toxoplasmic encephalitis (per 3/26/91 amendment, clindamycin arm was discontinued).
NCT00000714 ↗	An Open, Prospective, Multicenter Study of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia (PCP) and Serious Intolerance to Approved Therapies	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To determine the safety and effectiveness of an investigational drug therapy (trimetrexate plus leucovorin calcium (TMTX / LCV)) in the treatment of Pneumocystis carinii pneumonia (PCP) in patients who have AIDS, are HIV positive, or are at high risk for HIV infection, and who have suffered severe or life-threatening ill effects from both conventional therapies for PCP. AMENDED: 08/01/90 As of August 31, 1989, 437 patients were enrolled into uncontrolled studies of trimetrexate for PCP:214 in TX 301/ACTG 0=039 (trimetrexate for patients intolerant of approved therapies) and 223 in NS 401 (trimetrexate for patients refractory to approved therapies). The analysis of overall response rate, stringently defined as having received at least 14 days of trimetrexate and being alive at follow-up 1 month after the completion of therapy, reveals 84/159 intolerant patients and 48/160 refractory patients had responded, for rates of 53 percent and 30 percent, respectively. These response rates include all individuals who received at least one dose of trimetrexate. Of the 111 patients who were ventilator-dependent at study entry, 18 completed a course of therapy and were alive a month later, for a response rate of 16 percent. All other ventilated patients died. The most common severe (grades 3 and 4) toxicities were: transaminase elevation (> 5 x normal) in 94 patients, anemia (< 7.9 g/dl) in 109, neutropenia (< 750 cells/mm3) in 58, fever (> 40 C) in 37, and thrombocytopenia (< 50000 platelets/mm3) in 27. Toxicity required discontinuation of therapy in approximately 5 percent of all patients. Original design: The drugs usually used to treat PCP in AIDS patients, trimethoprim / sulfamethoxazole and pentamidine, have had to be discontinued in many patients because of severe side effects. Currently there are no proven alternatives to these drugs. TMTX was chosen for this trial because it was found to be very active against the PCP organism in laboratory tests. Also TMTX, in combination with LCV, had a high response rate and did not cause severe toxicity in a preliminary trial.

Clinical Trial Conditions for SULFAMETHOXAZOLE AND TRIMETHOPRIM

Condition Name

Condition Name for SULFAMETHOXAZOLE AND TRIMETHOPRIM
Intervention	Trials
HIV Infections	36
Pneumonia, Pneumocystis Carinii	27
Urinary Tract Infections	10
Urinary Tract Infection	8

Condition MeSH

Condition MeSH for SULFAMETHOXAZOLE AND TRIMETHOPRIM
Intervention	Trials
HIV Infections	39
Infections	39
Pneumonia	38
Infection	34

Clinical Trial Locations for SULFAMETHOXAZOLE AND TRIMETHOPRIM

Trials by Country

Trials by Country for SULFAMETHOXAZOLE AND TRIMETHOPRIM
Location	Trials
United States	402
Canada	16
China	16
France	16
Mexico	7

Trials by US State

Trials by US State for SULFAMETHOXAZOLE AND TRIMETHOPRIM
Location	Trials
California	33
New York	25
Illinois	24
Pennsylvania	20
Ohio	20

Clinical Trial Progress for SULFAMETHOXAZOLE AND TRIMETHOPRIM

Clinical Trial Phase

Clinical Trial Phase for SULFAMETHOXAZOLE AND TRIMETHOPRIM
Clinical Trial Phase	Trials
PHASE4	9
PHASE2	2
PHASE1	1

Clinical Trial Status

Clinical Trial Status for SULFAMETHOXAZOLE AND TRIMETHOPRIM
Clinical Trial Phase	Trials
Completed	87
Recruiting	19
Terminated	14

Clinical Trial Sponsors for SULFAMETHOXAZOLE AND TRIMETHOPRIM

Sponsor Name

Sponsor Name for SULFAMETHOXAZOLE AND TRIMETHOPRIM
Sponsor	Trials
National Institute of Allergy and Infectious Diseases (NIAID)	31
Glaxo Wellcome	8
National Cancer Institute (NCI)	7

Sponsor Type

Sponsor Type for SULFAMETHOXAZOLE AND TRIMETHOPRIM
Sponsor	Trials
Other	189
NIH	52
Industry	41

Last updated: July 27, 2026

Sulfamethoxazole and Trimethoprim (Co-Trimoxazole) Clinical Trials Update, Market Analysis, and 2030+ Revenue Projections

Sulfamethoxazole and trimethoprim (SMX/TMP, co-trimoxazole) remains a mature, off-patent anti-infective combination with broad generics coverage, limited brand-driven R&D, and ongoing clinical work focused on antimicrobial stewardship, resistance surveillance, dosing strategies, and specific high-value indications (notably Pneumocystis jirovecii pneumonia prophylaxis and treatment). Market growth is constrained by generic competition and guideline-driven usage patterns, but demand is supported by chronic use in HIV, immunosuppression, and respiratory infection pathways. Revenue upside from 2025 onward is primarily substitution into newer care settings and uptake of fixed-dose combinations and higher-strength regimens rather than premium pricing.

---

What clinical trials are ongoing for sulfamethoxazole and trimethoprim in 2025-2026?

Which trial categories are most active

For a mature generic like SMX/TMP, trial activity is typically dominated by:

• Comparative trials versus other oral antibiotics for community and outpatient respiratory infections (where SMX/TMP remains an option depending on resistance patterns).
• Dosing optimization trials (interval adjustments, weight-based dosing, pharmacokinetic/pharmacodynamic modeling).
• Safety and tolerability studies in special populations (renal impairment, pediatrics, pregnancy exposure characterization, immunocompromised cohorts).
• Prophylaxis trials in HIV and transplant contexts, often as part of broader infection-prevention studies rather than standalone SMX/TMP programs.
• Studies targeting antimicrobial resistance dynamics, including stewardship protocols that incorporate SMX/TMP selection rules.

What endpoints dominate

Common endpoints across these trials:

• Clinical cure rates at predefined follow-up windows.
• Microbiological eradication or pathogen clearance where culture is available.
• Treatment failure and relapse within short windows (typically 14 to 30 days).
• Safety events of interest for SMX/TMP: rash, serious cutaneous adverse reactions, hypersensitivity, cytopenias, renal adverse events, and hyperkalemia.

Trial signal quality expectations for SMX/TMP

Because SMX/TMP is off-patent, sponsor incentives lean toward pragmatic designs, registry-linkage studies, and investigator-initiated work. Trial packages tend to emphasize:

• Real-world comparators from standard-of-care lists.
• Health-system outcomes such as readmission, antibiotic switching rates, and stewardship adherence.

---

Which FDA-approved indications drive sulfamethoxazole and trimethoprim demand?

Core usage areas

SMX/TMP demand is concentrated in indications where clinicians need:

• Effective coverage for susceptible Gram-positive and Gram-negative bacteria and certain opportunistic pathogens.
• Oral options with predictable cost economics versus newer branded agents.

Key demand anchors (U.S. prescribing patterns generally emphasize):

• Pneumocystis jirovecii pneumonia (PJP): prophylaxis and treatment in immunocompromised patients, especially HIV and transplant populations.
• Respiratory and urinary tract infections: where local susceptibility supports SMX/TMP selection.
• Skin and soft tissue infections: depending on community resistance and guideline alignment.

Formulation-driven utilization

• Oral tablets
• Oral suspension (pediatrics, dosing flexibility)
• Fixed-dose combinations (including higher strengths)

Choice among formulations affects compliance and institutional prescribing, especially for pediatric dosing.

---

What is the Orange Book status of sulfamethoxazole and trimethoprim?

SMX/TMP is widely available as multiple approved generic products. The practical Orange Book outcome for market access is:

• No meaningful brand exclusivity barrier for systemic SMX/TMP formulations beyond product-specific exclusivities granted decades ago.
• Competition is shaped by ANDA supply, bioequivalence, package-level formulations, and occasionally formulation-specific patents or non-patent exclusivities that apply narrowly to particular presentations.

For forecasting and launch-risk purposes, market entry risk is primarily manufacturing quality, supply chain reliability, and distribution contracts rather than regulatory exclusivity.

---

When does sulfamethoxazole and trimethoprim lose exclusivity?

SMX/TMP is effectively beyond mainstream exclusivity constraints:

• The active ingredients are off-patent.
• The dominant competitive feature is generic availability and substitution economics.
• Any remaining exclusivity applies at a narrow product presentation level, not to the core active ingredient combination as an enterprise.

---

How many patents cover sulfamethoxazole and trimethoprim and what does that mean for competition?

Patent estate reality for off-patent combination antibiotics

For combination antibiotics like SMX/TMP, patent coverage commonly fragments into:

• Formulation patents (specific ratios, dissolution improvements, excipient systems).
• Process patents (manufacturing conditions).
• Indication-specific patents (less common for entrenched guideline uses).
• Packaging and stability improvements.

Commercial implication:

• Patent strategies tend to be defensive and tactical rather than game-changing.
• Most market participants route around via generic bioequivalent products or use established manufacturing know-how.

---

What generic entry risks exist for sulfamethoxazole and trimethoprim?

There is no “Paragraph IV” landscape that resembles brand-to-generic transitions for SMX/TMP. Entry risk instead concentrates on:

• FDA inspection outcomes for manufacturing sites.
• Stability, dissolution, and bioequivalence performance for specific strengths and formulations.
• Supply constraints that can create temporary price increases even with many players.

In practical terms, generic competition is limited by production capacity, quality systems, and distributor contracting rather than patent litigation.

---

What patent litigation affects sulfamethoxazole and trimethoprim?

For SMX/TMP, litigation is generally:

• Less centralized around core active ingredient exclusivity.
• More about localized formulation/process disputes or individual product-specific IP.

Because broad-market barriers are weak, litigation rarely produces multi-year exclusivity windows. If litigation occurs, it typically affects specific SKUs, not the overall category volume.

---

How does sulfamethoxazole and trimethoprim compare with amoxicillin-clavulanate, doxycycline, and fluoroquinolones?

Category-level economics

• SMX/TMP is priced at generic levels and competes on cost per treatment course and oral availability.
• Comparator selection depends on local resistance, patient allergy profiles, and contraindications.

Resistance and stewardship impact

• Increased resistance in key organisms reduces use in certain settings.
• Stewardship programs sometimes restrict SMX/TMP to susceptibility-guided prescribing or specific clinical syndromes.

Clinical differentiation

• SMX/TMP has distinct safety considerations (hypersensitivity, cytopenias, renal effects) that influence clinician choice in high-risk patients.
• When susceptibility is favorable, SMX/TMP remains an effective cost-efficient option.

---

What does the market for sulfamethoxazole and trimethoprim look like by segment?

Demand segmentation by setting

• Outpatient infections (high volume, high substitution sensitivity)
• Hospital inpatient use (conditional on formulary, renal monitoring protocols)
• Immunocompromised prophylaxis (lower prescriber frequency but more stable, repeat-course behavior)

Demand segmentation by formulation

• Tablets dominate adult use
• Suspension supports pediatric and dose-flexible pathways
• Higher-strength regimens influence institutional purchasing

Geography and distribution

SMX/TMP is globally available and competes with locally manufactured generics. Price competition drives regional variation more than formulation innovation.

---

Market projection: what growth rate and revenue range is realistic for sulfamethoxazole and trimethoprim through 2030?

Projection framework for off-patent generics

SMX/TMP category revenue typically tracks:

• Underlying infectious disease incidence and guideline-driven antibiotic selection.
• Total treated patients in prophylaxis cohorts (PJP prevention).
• Pricing pressure from generic entrants and periodic distributor contract resets.
• Mix shifts across strengths and formulation types.

Base-case projection (directional, category-level)

• Volume: steady-to-moderate growth driven by immunocompromised populations and outpatient treated populations, offset by antimicrobial stewardship limits in some syndromes.
• Price: flat to declining in aggregate due to steady generic competition, with occasional temporary price stabilization from manufacturing capacity constraints.

Resulting revenue expectation

For a mature generic antibiotic combination:

• Expect modest category revenue growth in nominal terms, primarily from volume stability and mild mix shifts.
• Expect real growth limited by price compression, with any step-changes tied to supply disruptions or stewardship-driven prescribing shifts.

---

What growth levers could change sulfamethoxazole and trimethoprim performance?

1. Immunocompromised prophylaxis continuity
   • HIV and transplant cohorts maintain ongoing demand.
2. Stewardship protocol fit
   • Protocol inclusion when local susceptibility supports SMX/TMP selection.
3. Supply and quality stability
   • Fewer disruptions can protect pricing and distributor availability.
4. Pediatric and higher-dose mix
   • Suspension utilization and dosing flexibility can increase use in certain care models.

---

What headwinds could pressure sulfamethoxazole and trimethoprim?

• Antimicrobial resistance
  • Reduces clinical utility for certain pathogens and syndromes.
• Safety/tolerability constraints
  • Hypersensitivity concerns can shift clinicians toward alternative agents in high-risk patients.
• Competition from newer oral agents
  • Even at generic pricing, alternative antibiotic classes may win formulary placements if stewardship benchmarks favor them.

---

How should investors and licensing teams underwrite sulfamethoxazole and trimethoprim exposure?

Underwriting assumptions

• Treat as a category with pricing pressure and supply-cycle volatility.
• Model growth mainly from cohort-driven prophylaxis persistence and outpatient volume stability.
• Value upside as operational: procurement advantages, reliable manufacturing, and formulary access.

Licensing implications

• Licensing upside is limited at the active ingredient level.
• Near-term monetization is most likely through:
  • Specialty formulations or line extensions
  • Distribution partnerships
  • Manufacturing know-how and capacity security

---

Key Takeaways

• SMX/TMP remains a mature off-patent antibiotic combination with stable demand anchored by prophylaxis and guideline-supported infections.
• Clinical trial activity is typically pragmatic and focused on dosing optimization, stewardship, and specific patient populations rather than brand-style innovation.
• Market growth is constrained by persistent generic competition, so revenue performance depends more on volume stability and supply reliability than premium pricing.
• The most material upside levers are immunocompromised prophylaxis persistence and mix shifts in formulation/strength, while major headwinds are resistance and tolerability-driven prescribing changes.

---

FAQs

Which organisms most influence sulfamethoxazole and trimethoprim prescribing in 2025?

Organisms tied to local susceptibility patterns and syndromes commonly evaluated for SMX/TMP suitability, such as urinary pathogens, respiratory Gram-negatives, and skin infection pathogens.

Does sulfamethoxazole and trimethoprim have meaningful biosimilar-style competition risk?

No. The product is a small-molecule antibiotic combination, so biosimilar frameworks do not apply.

What adverse events most affect sulfamethoxazole and trimethoprim utilization?

Hypersensitivity reactions, rash severity, cytopenias, renal adverse effects, and electrolyte disturbances that require monitoring.

How do renal impairment protocols affect real-world adherence to sulfamethoxazole and trimethoprim?

Renal monitoring and dose adjustments can change clinician selection and dosing compliance, impacting initiation and continuation rates.

Are there formulation strategies that can materially improve sulfamethoxazole and trimethoprim market access?

Improvements that support pediatric dosing flexibility, stability, and patient compliance, as well as reliable manufacturing supply, can influence distribution and formulary adoption.

---

References (APA)

1. FDA. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/daf/
2. ClinicalTrials.gov. (n.d.). Search results for sulfamethoxazole and trimethoprim. U.S. National Library of Medicine. https://clinicaltrials.gov/