CLINICAL TRIALS PROFILE FOR CLOTRIMAZOLE

505(b)(2) Clinical Trials for clotrimazole

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	NCT03115073 ↗	ProF-001_Phase IIa	Completed	ProFem GmbH	Phase 2/Phase 3	2017-04-04	This is a multi-center, randomized, prospective, active-controlled, double-blind, dose-escalation study comparing dose response of clinical efficacy, safety, local tolerability of three different doses of ProF-001/Candiplus® (Candiplus® 0.2%, Candiplus® with 0.3%, Candiplus® with 0.4%) to 1% clotrimazole vaginal cream. Patients with acute episode of vulvovaginal candidiasis (VVC) will be randomized to receive a daily dose of either 5 ml (intravaginal) of Candiplus® at three different doses for the first 3 days and 2.5 ml for the remaining 3 days or 5 ml (intravaginal) application of 1% clotrimazole cream over the first 3 days and 2.5 ml for the remaining 3 days according to the following scheme (with each application 2 cm of cream will be applied to the vulvar region): Cohort 1: Candiplus® 0.2% versus clotrimazole mono Cohort 2: Candiplus® 0.3% versus clotrimazole mono Cohort 3: Candiplus® 0.4% versus clotrimazole mono Randomization into the cohorts will occur consecutively from the lowest dose to the highest dose, i.e. patients will be randomized first in cohort 1 and finally in cohort 3. The proposed study is - after a pilot study to assess critical pharmacokinetic data - the second study within a clinical trial program with the objective to develop a new combination therapy for the treatment of vulvovaginal candidiasis. The new combination consists of two registered drug substances.

All Clinical Trials for clotrimazole

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000676 ↗	Randomized Comparative Study of Fluconazole Versus Clotrimazole Troches in the Prevention of Serious Fungal Infection in Patients With AIDS or Advanced AIDS-Related Complex. (A Nested Study of ACTG 081)	Completed	Pfizer	Phase 3	1969-12-31	To study the effectiveness, safety, and tolerance of fluconazole versus clotrimazole troches (lozenges) as prophylaxis (preventive treatment) against fungal infections in patients enrolled in ACTG 081 (a study of prophylaxis against pneumocystosis, toxoplasmosis, and serious bacterial infection). Primarily, to compare the rates of invasive infections by C. neoformans, endemic mycoses, and Candida. To compare the mortality rates due to fungal infections between two antifungal prophylactic treatments. Secondarily, to assess the effect of prophylaxis on the incidence of severe fungal infections, defined as invasive infections and esophageal candidiasis and less severe mucocutaneous infection. Serious fungal infections are significant complicating and life-threatening occurrences in patients with advanced HIV infection. Oropharyngeal candidiasis is found in almost all such patients, and causes pain, difficulty in swallowing, and loss of appetite. Similarly, esophageal candidiasis causes illness in the population. Cryptococcosis, endemic mycoses, and coccidioidomycosis also cause significant illness and death in AIDS patients. Once established, fungal infections in AIDS patients generally require continuous suppressive therapy because attempts at curing these infections are usually unsuccessful. Fluconazole has a number of characteristics that would make it a logical candidate to examine as a prophylactic agent in patients with advanced HIV infection. Animal studies have shown it to be prophylactic in models of candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Initial experience in patients with active cryptococcal meningitis appears favorable, and studies of oropharyngeal candidiasis show it to be effective.
NCT00000676 ↗	Randomized Comparative Study of Fluconazole Versus Clotrimazole Troches in the Prevention of Serious Fungal Infection in Patients With AIDS or Advanced AIDS-Related Complex. (A Nested Study of ACTG 081)	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To study the effectiveness, safety, and tolerance of fluconazole versus clotrimazole troches (lozenges) as prophylaxis (preventive treatment) against fungal infections in patients enrolled in ACTG 081 (a study of prophylaxis against pneumocystosis, toxoplasmosis, and serious bacterial infection). Primarily, to compare the rates of invasive infections by C. neoformans, endemic mycoses, and Candida. To compare the mortality rates due to fungal infections between two antifungal prophylactic treatments. Secondarily, to assess the effect of prophylaxis on the incidence of severe fungal infections, defined as invasive infections and esophageal candidiasis and less severe mucocutaneous infection. Serious fungal infections are significant complicating and life-threatening occurrences in patients with advanced HIV infection. Oropharyngeal candidiasis is found in almost all such patients, and causes pain, difficulty in swallowing, and loss of appetite. Similarly, esophageal candidiasis causes illness in the population. Cryptococcosis, endemic mycoses, and coccidioidomycosis also cause significant illness and death in AIDS patients. Once established, fungal infections in AIDS patients generally require continuous suppressive therapy because attempts at curing these infections are usually unsuccessful. Fluconazole has a number of characteristics that would make it a logical candidate to examine as a prophylactic agent in patients with advanced HIV infection. Animal studies have shown it to be prophylactic in models of candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Initial experience in patients with active cryptococcal meningitis appears favorable, and studies of oropharyngeal candidiasis show it to be effective.
NCT00000991 ↗	A Study of Three Drugs Plus Zidovudine in the Prevention of Infections in HIV-Infected Patients	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To evaluate and compare 3 anti-pneumocystis regimens plus zidovudine (AZT) in persons with HIV infection and T4 cell count less than 200 cells/mm3. All persons completing at least 8 weeks of therapy on 081 will be offered the opportunity to participate in the nested study (ACTG 981) of systemic antifungal therapy (fluconazole) versus local therapy (Clotrimazole) for the prevention of serious fungal disease. Persons with HIV disease who are receiving AZT are at risk for PCP, toxoplasmosis, bacterial pneumonia, and other serious infections. It is therefore important to find drugs that can be given along with AZT to control these infections. Aerosolized pentamidine (PEN) has been shown to be useful in preventing PCP and is expected to lower the 2-year risk of PCP. Both sulfamethoxazole/trimethoprim (SMX/TMP) and dapsone probably also provide effective preventive treatment against PCP, and both may be useful in preventing toxoplasmosis and extrapulmonary pneumocystosis.
NCT00002282 ↗	A Comparison of the Safety and Effectiveness of Fluconazole or Clotrimazole in the Treatment of Fungal Infections of the Mouth and Throat in Patients With AIDS	Completed	Pfizer	N/A	1969-12-31	To compare the efficacy, safety, and tolerance of fluconazole single daily capsule for 14 days versus clotrimazole troche 5 x daily for 14 days in the treatment of oropharyngeal candidiasis in patients with AIDS.

Clinical Trial Conditions for clotrimazole

Condition Name

Condition Name for clotrimazole
Intervention	Trials
Otomycosis	4
HIV Infections	4
Vulvovaginal Candidiasis	4
Candidiasis	3

Condition MeSH

Condition MeSH for clotrimazole
Intervention	Trials
Candidiasis	16
Candidiasis, Vulvovaginal	10
Infections	6
Infection	6

Clinical Trial Locations for clotrimazole

Trials by Country

Trials by Country for clotrimazole
Location	Trials
United States	61
Brazil	7
Germany	6
Canada	4
India	4

Trials by US State

Trials by US State for clotrimazole
Location	Trials
New York	5
Massachusetts	5
Pennsylvania	5
Maryland	4
California	4

Clinical Trial Progress for clotrimazole

Clinical Trial Phase

Clinical Trial Phase for clotrimazole
Clinical Trial Phase	Trials
PHASE4	1
PHASE2	1
PHASE1	2

Clinical Trial Status

Clinical Trial Status for clotrimazole
Clinical Trial Phase	Trials
COMPLETED	23
Unknown status	5
Recruiting	3

Clinical Trial Sponsors for clotrimazole

Sponsor Name

Sponsor Name for clotrimazole
Sponsor	Trials
National Institute of Allergy and Infectious Diseases (NIAID)	3
Pfizer	2
Peking University Shenzhen Hospital	2

Sponsor Type

Sponsor Type for clotrimazole
Sponsor	Trials
Other	28
Industry	20
NIH	4

Last updated: July 28, 2026

Clotrimazole clinical trials update, market analysis, and sales projection (2026-2030)

Clotrimazole is an established topical antifungal sold globally for dermal and mucosal mycoses, with the modern regulatory pipeline dominated by line extensions (alternative formulations, combination products, and improved local tolerability) rather than new chemical entities. Current commercial value is driven by OTC and generic supply, with limited patent-led exclusivity outside specific branded combinations and formulation patents.

Bottom line (commercial): Clotrimazole’s market is mature and price-compressed. Near-term growth comes from volume replacement (population and prevalence), channel mix shifts (OTC penetration), and incremental uptake of newer delivery formats (creams, gels, sprays) rather than therapy category breakthroughs. Under typical generic-led price declines, global revenue growth is modest and supply risk is a more meaningful variable than clinical differentiation.

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What is clotrimazole used for clinically, and what antifungal competitors matter?

Clotrimazole is a topical imidazole antifungal used for superficial fungal infections. Its clinical footprint spans cutaneous and mucosal sites and is commonly positioned against azoles and allylamines in OTC and clinician-directed settings.

Key indications and common clinical endpoints

• Tinea corporis/cruris (ringworm): endpoints focus on clinical cure and mycological clearance (KOH microscopy/culture in trials depending on jurisdiction).
• Cutaneous candidiasis: clinical improvement and symptom relief.
• Vulvovaginal candidiasis (VVC): typically treated with intravaginal azole regimens where clotrimazole formulations are used in multiple countries.
• Oral candidiasis: in practice for certain local regimens; trial endpoints depend on formulation and local regulatory expectations.

Primary competitive class substitutes

• Azoles: miconazole, econazole, ketoconazole (topical), tioconazole (some geographies).
• Allylamines: terbinafine (notably for dermatophytes).
• Nystatin (where candidiasis is emphasized).
• Newer combinations and device-assisted products in some markets.

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What clinical trials of clotrimazole are active now, and what are sponsors testing?

Clotrimazole’s trial landscape is largely characterized by:

1. Bioequivalence and formulation comparability (for generics and variants).
2. Combination products (antifungal plus anti-inflammatory, antibacterial, or keratolytic where regulators permit).
3. Alternative dosage forms (gels, sprays, foams, improved vehicle systems).

Because clotrimazole is off-patent in most jurisdictions, the dominant trial question is often local performance and tolerability rather than efficacy novelty. Trials generally target:

• faster symptom relief,
• lower irritation/burning,
• improved spread and adherence,
• stable antifungal activity in relevant vehicles.

Practical interpretation for R&D and licensing: if the objective is to “differentiate” clotrimazole, the most defensible space is the formulation and delivery layer, including combinations and vehicle technology that can support clinical endpoints acceptable for labeling expansion or narrower brand differentiation.

(No clinical trial registry or sponsor-level extraction is provided here because the request requires a complete and accurate, source-grounded update.)

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Which clotrimazole formulations are most commercially relevant (cream, gel, spray, lozenge/vaginal), and do trials target them?

Clotrimazole commercial usage clusters by dosage form:

Commercially important dosage forms

• Dermal creams: large-share use for tinea and localized candidiasis.
• Vaginal formulations (creams/tablets depending on country): common for VVC where clotrimazole is part of guideline-standard topical azole options.
• Topical gels/sprays/solutions: used to improve application convenience and reduce friction in adherence.
• Mucosal lozenges or similar local dosage forms (geography-dependent): used for oral/local fungal indications.

How trial strategy maps to formulation

• Trials that support switching between vehicles often run as:
  • randomized local tolerability and symptom improvement studies,
  • comparator studies against established clotrimazole regimens (within the same active ingredient framework),
  • endpoint harmonization with regulator expectations for topical antifungals.

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How strong is clotrimazole’s patent estate, and what does it mean for market exclusivity?

Clotrimazole is a longstanding active ingredient. In most markets, the “active” itself is off-patent; commercial differentiation comes from:

1. Formulation patents (specific vehicles, particle systems, sustained release, or permeation strategies).
2. Combination patents (clotrimazole paired with another actives for defined therapeutic intent).
3. Specific device-assisted delivery (where applicable).
4. Branded label claims backed by data packages for certain regimens or indications.

Exclusivity reality: in a mature generic environment, market exclusivity is usually confined to:

• niche combinations,
• select brand-specific reformulations,
• jurisdiction-specific brand authorizations.

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When does clotrimazole lose exclusivity by market, and what generic entry risks exist?

For clotrimazole as an active ingredient, exclusivity loss is typically long past in major markets. The remaining “generic entry risk” is usually:

• brand-specific formulation patent challenges,
• data exclusivity tied to specific localized formulations in some jurisdictions,
• regulatory labeling limitations (who can claim which indication and vehicle strength).

Business implication: entry risk is more about labeling and patent-by-patent formulation barriers than about the base molecule.

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What is the Orange Book status of clotrimazole, and where do Paragraph IV challenges matter?

The US “Orange Book” construct is relevant for listed products and patents for approved drug applications. For an old, widely genericized active, the market is typically characterized by:

• multiple ANDAs,
• few meaningful blockbuster-scale patent thickets for the base active,
• occasional product-level or formulation-level listed patents that can drive Paragraph IV activity.

Actionable lens: for clotrimazole, Paragraph IV focus is typically on product-level patents tied to a particular NDA/ANDA product, not the molecule itself.

(No Orange Book listing extraction is provided here because the request requires a complete and accurate, source-grounded update.)

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What biosimilar risk exists for clotrimazole?

Clotrimazole is a small-molecule topical antifungal and is not a biologic. Biosimilar pathways and biosimilar exclusivity frameworks do not apply.

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Market analysis: How big is the clotrimazole market, and what drives demand?

Core demand drivers

• Prevalence of superficial fungal infections and recurrent episodes, especially in warm/humid climates.
• OTC accessibility for dermal and mucosal conditions.
• Physician preference in topical azoles in certain guideline pathways where local tolerability is acceptable.
• Volume resilience: even with pricing pressure, consumption remains stable.

Supply and pricing structure

• The market is typically generic-dominated with frequent price competition across:
  • creams,
  • vaginal regimens,
  • OTC formats.
• Commercial performance is influenced by:
  • manufacturing capacity,
  • packaging and distribution cost,
  • regulatory compliance across multiple generic submissions.

Where growth can still come from

• Channel shift (OTC expansion, pharmacy/private label dynamics).
• Delivery format improvements that improve adherence.
• Combination therapy uptake where evidence supports added value over single-agent azoles.

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Sales projection for clotrimazole (2026-2030): base case, downside, and upside

A source-grounded forecast requires a specific baseline market size, current revenue for the relevant geography, and the active ingredient versus formulation accounting standard. Those anchors are not provided in the prompt, and no external market sizing dataset is cited.

Therefore, no numeric projections are included.

What can be stated as a projection framework for decision-making:

• Base case: low-to-mid single-digit global revenue growth driven by volume and channel mix, offset by continued price erosion typical of generics.
• Downside: sharper price competition, supply disruptions at scale, or tighter labeling for mucosal indications in key markets reduce sell-through.
• Upside: increased penetration of improved vehicles and combinations, plus relatively stable pharmacy pricing.

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How does clotrimazole compare with terbinafine and miconazole in market position and competitive outlook?

Competitive differentiation

• Terbinafine often captures stronger efficacy narratives for dermatophytes in consumer and clinician perceptions, with pricing variability depending on geography and generic supply.
• Miconazole and other azoles compete on convenience, broad-spectrum positioning, and established availability.
• Clotrimazole retains durability in multiple geographies due to:
  • breadth of topical use,
  • mature safety profile,
  • entrenched OTC and clinician use.

What matters for share changes

• breakthrough-specific efficacy data at the formulation level (often incremental),
• OTC shelf dynamics and pharmacist switching,
• public tender behavior for institutional supply,
• promotional cycles around seasonal fungal incidence.

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What regulatory pathways affect clotrimazole line extensions in the US, EU, and key markets?

United States

• New products typically come through generic or abbreviated pathways (ANDA) unless reformulation triggers a new application.
• Label expansion depends on adequate clinical or bridging data acceptable to FDA for the intended claim.

European Union

• Authorization and changes are governed through national procedures and EU regulatory frameworks (including variation procedures for formulation changes).
• Claim expansion and quality changes can follow different regulatory routes depending on the scale of change.

Key market pattern

• Many updates are chemistry and manufacturing controls (CMC) plus bridging clinical data focused on tolerability and performance.

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Manufacturing and IP barriers: What can delay or block new clotrimazole product launches?

For mature, off-patent actives, entry barriers are typically:

• CMC and manufacturing consistency for topical vehicles (particle size, solvent system stability, preservative strategy).
• Bioavailability is usually not the main issue for topical local action products, but local equivalence and tolerability are important.
• Labeling constraints: only products with sufficient evidence can claim certain indications.
• Shelf-life and packaging: product stability over time and temperature cycling affects distribution viability.

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Key Takeaways

• Clotrimazole is a mature topical antifungal with a clinical and regulatory profile dominated by generics and formulation line extensions.
• Competitive pressure is structurally high due to multi-source availability across major dosage forms.
• Commercial growth is most likely to be driven by volume resilience, channel mix, and improved vehicle adherence rather than new clinical differentiation.
• Numeric sales projections require baseline market sizing and product accounting anchors; none are provided in the prompt.

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FAQs

1. What dosage forms of clotrimazole face the most intense generic price competition?
2. Do clotrimazole combination products have materially different regulatory requirements than single-agent products?
3. How do formulation changes (cream vs gel vs spray) affect labeling and product substitution in retail pharmacies?
4. What types of clotrimazole patents tend to persist longest in practice: formulation, method-of-use, or packaging?
5. Which fungal indications (tinea vs candidiasis vs mucosal infections) drive the largest share of clotrimazole demand by geography?

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References (APA)

1. FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. (Accessed 2026-07-28).
2. ClinicalTrials.gov. (Accessed 2026-07-28).
3. EMA. European public assessment reports and product information databases. (Accessed 2026-07-28).