CLINICAL TRIALS PROFILE FOR TRIMETHOPRIM

505(b)(2) Clinical Trials for 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 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.

Clinical Trial Conditions for trimethoprim

Condition Name

Condition Name for trimethoprim
Intervention	Trials
HIV Infections	36
Pneumonia, Pneumocystis Carinii	27
Urinary Tract Infections	11

Condition MeSH

Condition MeSH for trimethoprim
Intervention	Trials
Infections	42
Pneumonia	41
HIV Infections	39

Clinical Trial Locations for trimethoprim

Trials by Country

Trials by Country for trimethoprim
Location	Trials
United States	445
Canada	21
China	16
France	16
Netherlands	12

Trials by US State

Trials by US State for trimethoprim
Location	Trials
California	35
New York	27
Pennsylvania	24
Illinois	24
Ohio	23

Clinical Trial Progress for trimethoprim

Clinical Trial Phase

Clinical Trial Phase for trimethoprim
Clinical Trial Phase	Trials
PHASE4	9
PHASE2	5
PHASE1	2

Clinical Trial Status

Clinical Trial Status for trimethoprim
Clinical Trial Phase	Trials
Completed	105
Recruiting	29
Terminated	15

Clinical Trial Sponsors for trimethoprim

Sponsor Name

Sponsor Name for trimethoprim
Sponsor	Trials
National Institute of Allergy and Infectious Diseases (NIAID)	32
Glaxo Wellcome	8
National Cancer Institute (NCI)	7

Sponsor Type

Sponsor Type for trimethoprim
Sponsor	Trials
Other	255
NIH	55
Industry	53

Trimethoprim Clinical Trials Update, Market Analysis, and Projection (2026-2035)

Last updated: July 28, 2026

Trimethoprim remains a mature, largely off-patent antibacterial active ingredient. Clinical-trials activity is episodic and dominated by observational studies, comparative studies in routine care, and formulation or regimen evaluation rather than new broad-spectrum discovery. Commercial demand is anchored by older combinations (notably trimethoprim-sulfamethoxazole) and sustained access in community and long-term care settings; growth is driven more by market penetration and supply stability than by new therapeutic indications.

What clinical trials are currently recruiting or recently completed for trimethoprim?

Trimethoprim’s modern clinical footprint typically clusters into three buckets: (1) antimicrobial regimen comparisons using trimethoprim-based combinations, (2) pharmacokinetic or formulation work (bioavailability, dissolution, stability), and (3) resistance and real-world effectiveness studies. Standalone trimethoprim monotherapy trials are less common than combination studies, because TMP-SMX is the primary branded and guideline-recommended regimen in many indications.

Featured snippet answer: Clinical development for trimethoprim is concentrated in regimen comparison, formulation evaluation, and real-world outcomes rather than new chemical entities or new molecular targets.

Trial activity patterns to watch

• PK/bioavailability: studies assessing absorption, food effects, and equivalence across generic products or reformulations.
• Susceptibility and resistance surveillance: work that updates local or country-level resistance patterns and links them to clinical outcomes.
• Special populations: renal impairment, pediatrics, and older adults, where dosing and toxicity monitoring affect outcomes.
• Combination regimens: trimethoprim used with sulfamethoxazole for urinary tract infections, respiratory infections (where susceptible), and prophylaxis in selected risk groups.

How to interpret “clinical trials updates” for a mature API

Because trimethoprim is long-established, trial updates are more likely to impact:

• Formulation approvals (quality-by-design or equivalence),
• Stewardship guidance (where susceptibility supports or constrains use),
• Guideline positioning (comparative effectiveness vs. alternative antibiotics).

Which indications have the strongest evidence base for trimethoprim use today?

Trimethoprim’s main commercial relevance is built on clinical guideline use for infections susceptible to TMP-SMX, with trimethoprim also used where monotherapy is an option.

Typical high-use indication clusters

• Uncomplicated urinary tract infections (UTIs): usually via TMP-SMX depending on resistance patterns and local guidance.
• Prophylaxis: trimethoprim-based prophylaxis is used in preventive strategies for specific immunocompromised populations where recommended.
• Skin and soft tissue infections: where susceptible organisms align with local antibiograms.
• Alternative regimens: in penicillin-allergic pathways or when stewardship supports narrow-spectrum options.

Featured snippet answer: The highest utilization and evidence density for trimethoprim is tied to TMP-SMX-driven practice, guided by antibiograms and stewardship.

What determines current clinical positioning

• Local resistance rates to susceptible pathogens
• Renal function and adverse-event monitoring
• Drug availability and stewardship constraints (substitution pressures)

What is the current market size for trimethoprim and how is it split between monotherapy and combinations?

Trimethoprim is generally sold as:

• Trimethoprim-sulfamethoxazole (TMP-SMX) combinations (most commercially significant use)
• Trimethoprim monotherapy (smaller share in many markets)

A useful market framing for decision-making is the separation between:

• API and generic solid oral dosage supply, and
• Finished-dose TMP-SMX product demand, which drives procurement volumes.

Featured snippet answer: Demand is concentrated in TMP-SMX finished products, with trimethoprim monotherapy representing a smaller, more variable share by geography and guideline preference.

Where volume tends to concentrate

• Community antibiotics: outpatient UTI and mixed infection pathways where susceptibility supports use.
• Long-term care: prophylaxis and recurrent infection pathways.
• Institutional formularies: steady procurement where generics are entrenched.

How does trimethoprim market growth compare with alternative antibiotics (fluoroquinolones, nitrofurantoin, beta-lactams)?

Trimethoprim competes primarily on price, oral convenience, and guideline standing, with usage constrained by resistance.

Competitive dynamics

• Fluoroquinolones: usage may shift with stewardship restrictions; trimethoprim can gain share in settings where resistance or safety policies favor older oral agents.
• Nitrofurantoin: often absorbs UTI-specific prescribing; trimethoprim shares overlap in uncomplicated UTI decision pathways but is exposed to different resistance profiles.
• Beta-lactams: remain common; trimethoprim faces substitution pressure but persists where allergy pathways exist or where TMP-SMX remains guideline-supported.

Featured snippet answer: Trimethoprim growth is typically incremental and substitution-driven, not innovation-led.

When does trimethoprim lose exclusivity and what does that mean for generics?

As an older active ingredient, trimethoprim is effectively off the exclusivity curve in most jurisdictions for the core API and standard oral formulations. Practical exclusivity is limited to:

• Specific formulation patents (if any still exist for certain salts/ratios or manufacturing processes)
• Indication-specific exclusivities (rare for this mature agent, unless tied to a specific combination product lifecycle)
• Data exclusivity attached to particular submissions (now largely expired for most products in established markets)

Featured snippet answer: Trimethoprim is largely out of active exclusivity, so competitive pressure is driven by generic penetration and formulation patent islands rather than platform-level exclusivity expiry.

Generic entry implications

• Price compression is the base case.
• Supply chain stability and quality system execution matter more than branded differentiation.
• Patent litigation is generally less central than for newer small molecules, though it can arise around specific dosage forms or manufacturing methods.

What formulations are protected by patents for trimethoprim and trimethoprim-sulfamethoxazole?

For mature generics, patent coverage usually falls into narrow areas:

• Solid oral formulation compositions (excipients, particle size specifications, release characteristics)
• Manufacturing process patents (granulation, milling, drying profiles)
• Bioequivalence-related formulation specifications (less frequently patentable, but can support process claims)

Featured snippet answer: Patent protection for trimethoprim in 2026 is typically formulation- and process-specific rather than covering the core drug entity broadly.

Actionable IP lens for business decisions

• Map product-specific Orange Book and counterpart filings for TMP-SMX generics by strength (e.g., 80/400 mg, 160/800 mg), dosage form, and manufacturer.
• Identify any remaining formulation patent “islands” that can affect launch timing in specific countries.
• Treat endpoint litigation risk as product- and manufacturer-specific, not platform-wide.

What is the Orange Book status of trimethoprim-based products?

Orange Book status is product- and NDA/BLA-specific. For trimethoprim-based products, the practical commercial landscape is dominated by:

• Multiple ANDAs with listed patents already expired or close to expiry
• Limited ongoing listed-patent leverage for core oral TMP-SMX products

Featured snippet answer: Orange Book coverage for trimethoprim combinations is generally mature, with most competitive products sitting on expired or expiring patent estates and a stable generic ecosystem.

How business teams typically use Orange Book for trimethoprim

• Confirm whether a specific TMP-SMX NDA still has listed patents and their expiration windows.
• Identify any active Paragraph IV litigation and resulting settlement terms for that exact product/strength.

Which companies are challenging patents or entering with Paragraph IV for trimethoprim products?

For mature drugs, Paragraph IV activity is usually sporadic and concentrated around:

• Certain strengths or dosage forms
• New generic applicants targeting a specific listed-patent blocking position
• Reformulated products or different release profiles

Featured snippet answer: Paragraph IV challenges for trimethoprim-based products tend to be product-specific and less frequent than for newer therapies; the dominant risk is still around formulation/process patents rather than the drug substance.

What generic entry risks exist for trimethoprim monotherapy and TMP-SMX?

Generic entry risk is typically driven by:

• Unexpired formulation/process patents
• Therapeutic-equivalence constraints if label dosing differs among competitors
• Manufacturing deviations that threaten approval timetables
• Labeling or safety differences that trigger dispute over the ANDA reference listed drug (RLD) profile

Featured snippet answer: For trimethoprim-based generics, the biggest entry risks are narrower patent islands and manufacturing compliance rather than broad platform exclusivity.

How does trimethoprim compare with competing antibiotics on safety, resistance, and stewardship constraints?

Trimethoprim is associated with class-specific tolerability considerations, with clinically meaningful risks such as hypersensitivity and hematologic or renal adverse effects in susceptible populations.

Stewardship and resistance

• Trimethoprim use depends heavily on local susceptibility data.
• Resistance patterns can materially reduce guideline utility and shift prescribing to alternatives.

Featured snippet answer: Trimethoprim is primarily constrained by resistance and tolerability considerations; prescribing remains protocol-anchored and antibiogram-dependent.

Decision-impacting endpoints in clinical practice

• Rate of clinical cure vs alternatives
• Adverse event rates in renal impairment and in older adults
• Microbiologic eradication aligned with local resistance

What is the regulatory landscape for trimethoprim in major markets (FDA, EMA, UK, Canada)?

Regulatory status is dominated by:

• ANDA approvals for generic TMP-SMX products
• Ongoing quality monitoring (sterility not usually relevant for oral generics, but dissolution, content uniformity, stability are)
• Periodic safety label updates reflecting post-marketing data across the class

Featured snippet answer: Regulation focuses on generic quality systems and label consistency; innovation-driven regulatory milestones are limited for the mature active ingredient.

Pathway implications

• New entrants are typically abbreviated programs with bioequivalence and chemistry controls.
• Post-approval commitments can extend timelines, affecting commercial ramp.

What is the most credible market projection for trimethoprim through 2035?

Base case projection (directional):

• Nominal market value: low-to-mid single-digit CAGR depending on price erosion vs volume stability.
• Units: relatively stable to modest growth, supported by recurring infection incidence and continued reliance on TMP-SMX.
• Market share: shifts based on antibiogram-driven guideline use and substitution among oral antibiotics.

Featured snippet answer: Trimethoprim is likely to grow modestly in value and stay volume-stable to slightly up, with growth constrained by pricing pressure and resistance-driven prescribing shifts.

Scenario framework (business planning)

• Upside: improved stewardship alignment, stable supply, sustained TMP-SMX guideline inclusion in key geographies; modest penetration growth in outpatient settings.
• Base case: continued price compression, stable volume; limited formulation-driven differentiation.
• Downside: resistance increases reduce empirical use; competitive substitution to nitrofurantoin or other preferred agents; supply disruptions or regulatory action in specific manufacturing sites.

What revenue exposure does a trimethoprim business face if a key generic loses market or faces supply constraints?

Because the active ingredient is mature and competitively supplied, revenue exposure concentrates in:

• Contract manufacturing and supply agreements
• Regional tender wins that lock in pricing and volume
• Safety or quality incidents that can cause immediate formulary pull, even when patent risk is absent

Featured snippet answer: Revenue risk is operational and contractual, not primarily IP-driven, for most trimethoprim businesses.

Key Takeaways

• Trimethoprim clinical activity is mature and episodic, dominated by regimen comparison, formulation, PK/BE, and real-world outcomes rather than new therapeutic breakthroughs.
• Commercial demand is anchored in TMP-SMX combinations; monotherapy is smaller and more geography-dependent.
• Exclusivity is largely expired; generic economics dominate, with business risk shifting to product-specific formulation/process patent islands and execution.
• Market outlook through 2035 is modest growth in value with constrained upside due to resistance-driven prescribing and persistent price pressure.

FAQs

1. What are the most common trial endpoints used in trimethoprim or TMP-SMX studies?
2. How do resistance rates change empiric trimethoprim use in uncomplicated UTIs?
3. Which dosing populations drive most safety-monitoring during trimethoprim therapy?
4. What manufacturing or quality issues most often delay generic TMP-SMX launches?
5. How does trimethoprim’s market position differ between the US and EU/UK?

References

1. U.S. FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. (Accessed 2026-07-28). https://www.accessdata.fda.gov/scripts/cder/daf/
2. ClinicalTrials.gov. Trimethoprim and trimethoprim-sulfamethoxazole search results. (Accessed 2026-07-28). https://clinicaltrials.gov/
3. World Health Organization. Antimicrobial resistance and antibiotic stewardship resources (general framework). (Accessed 2026-07-28). https://www.who.int/health-topics/antimicrobial-resistance