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
HIV Infections	4
Vulvovaginal Candidiasis	4
Candidiasis	3
Otomycosis	3

Condition MeSH

Condition MeSH for Clotrimazole
Intervention	Trials
Candidiasis	16
Candidiasis, Vulvovaginal	9
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
Pennsylvania	5
New York	5
Massachusetts	5
Ohio	4
North Carolina	4

Clinical Trial Progress for Clotrimazole

Clinical Trial Phase

Clinical Trial Phase for Clotrimazole
Clinical Trial Phase	Trials
Phase 4	7
Phase 3	12
Phase 2/Phase 3	3

Clinical Trial Status

Clinical Trial Status for Clotrimazole
Clinical Trial Phase	Trials
Completed	22
Unknown status	5
Withdrawn	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	26
Industry	19
NIH	4

Clinical Trials Update, Market Analysis, and Projection for Clotrimazole

Last updated: October 27, 2025

Introduction

Clotrimazole, a broad-spectrum antifungal agent from the azole class, remains a critical player in the management of superficial fungal infections. First introduced in the 1970s, clotrimazole's enduring presence in the pharmaceutical landscape underpins its established efficacy and safety profile. With evolving dermatological and gynecological treatment paradigms, continuous clinical evaluation and market assessment are vital. This analysis synthesizes current clinical trial statuses, market dynamics, and future projections to inform stakeholders about clotrimazole’s trajectory in the global pharmaceutical sector.

Clinical Trials Overview

Current Status of Clotrimazole Clinical Trials

Clotrimazole has traditionally been administered topically, and despite its longstanding use, ongoing research seeks to explore new delivery modalities and indications. As of mid-2023, clinical trial registries such as ClinicalTrials.gov and EU Clinical Trials Register document limited active studies focusing specifically on clotrimazole, primarily centered on formulation innovations and combination therapies.

• Formulation Development: Several Phase I and II trials investigate novel delivery systems, such as nanoemulsions, liposomal formulations, and transdermal patches, aimed at enhancing bioavailability and patient compliance. For instance, a trial (NCT05005295) evaluates a liposomal clotrimazole cream for treating dermatophyte infections, demonstrating the drug's ongoing pursuit of improved topical efficacy.

• Combination Therapies: Studies exploring clotrimazole alongside other antifungals or anti-inflammatory agents are underway. An example includes a trial assessing clotrimazole with betamethasone for dermatological conditions, seeking to optimize therapeutic outcomes while minimizing side effects.

• New Indications & Routes of Administration: While limited, some early-phase trials assess oral or intravaginal formulations for systemic or target-specific applications, reflecting exploratory efforts to broaden clotrimazole’s clinical utility.

Recent Findings and Implications

Research indicates that these novel delivery methods may improve drug penetration, reduce dosing frequency, and potentially lower adverse effects. However, to date, no large-scale Phase III clinical trials or pivotal studies have been published, suggesting the product remains primarily positioned within established topical uses.

Market Analysis

Global Market Landscape

Clotrimazole maintains a significant share in the antifungal segment, particularly for superficial skin infections like athlete’s foot, candidiasis, and tinea corporis. The compound’s low cost, widespread availability, and existing off-patent status contribute to its extensive adoption.

• Market Size & Growth: The global antifungal market was valued at approximately USD 15 billion in 2022, with topical formulations accounting for a substantial segment. Clotrimazole, predominantly marketed as brand-name products such as Lotrimin and generic equivalents, captures an estimated 20-25% of topical antifungal sales.

• Key Regions: North America and Europe lead with high dermatological care standards, but emerging markets in Asia-Pacific show rapid growth driven by increasing dermatological conditions and expanding healthcare infrastructure.

Competitive Landscape

Clotrimazole faces competition from other azoles such as miconazole, econazole, and newer antifungals like terbinafine and butenafine. While these competitors often offer improved pharmacokinetics or broader spectrum activity, clotrimazole benefits from established clinical familiarity and lower procurement costs.

• Genericization: The expiration of patents substantially increased market competition, encouraging generic manufacturing and intensifying price competition, which benefits consumers and healthcare providers.

Regulatory Environment

Regulatory pathways for topical antifungals are streamlined in many jurisdictions; however, approval processes for new formulations or indications are rigorous. Post-market surveillance continues to confirm safety profiles, which bolster market confidence.

Future Market Projections

Growth Drivers

• Evolving Formulations & Delivery Systems: Innovations in nano-delivery and combination therapies hold promise for expanding clotrimazole’s utility, potentially leading to new patent opportunities and premium pricing for advanced formulations.

• Increasing Prevalence of Fungal Infections: A rise in immunosuppressive therapies, the COVID-19 pandemic’s impact on secondary fungal infections, and growing awareness bolsters demand for effective antifungals.

• Expanding Applications: Preliminary research exploring systemic uses or combination regimens could unlock new indications and markets.

Challenges & Market Limitations

• Competitive Pressure: The influx of newer antifungals with broader spectra or superior pharmacodynamics could erode clotrimazole’s market share.

• Resistance Development: Although currently rare, increasing reports of antifungal resistance could impact efficacy perceptions.

• Regulatory & Patent Constraints: Limited opportunities for patent protection restrict premium pricing and market exclusivity unless new formulations are developed.

Market Projection (2023-2030)

Considering these factors, the global clotrimazole market is expected to grow at a CAGR of approximately 3-5%. The growth will be driven mainly by formulation innovation and expanding use in emerging markets. The Asia-Pacific region is anticipated to lead growth due to rising prevalence rates and healthcare infrastructure development.

Strategic Opportunities & Recommendations

• Investment in Novel Formulations: Companies should prioritize research into advanced delivery systems to differentiate products and extend market life.

• Expansion into Adjacent Indications: Exploring systemic or alternative routes of administration could unlock new revenue streams.

• Market Penetration in Emerging Economies: Tailoring pricing strategies and improving distribution channels can capitalize on rising demand in these markets.

• Regulatory Engagement: Collaborating with authorities for faster approval of innovative formulations can expedite market entry.

Key Takeaways

• Current Clinical Status: Ongoing trials focus on enhancing delivery systems and combination therapies; large-scale studies are absent, emphasizing the drug’s established topical niche.

• Market Position: As a low-cost, off-patent antifungal, clotrimazole remains a staple in superficial fungal infection management worldwide, with significant presence in developed markets and growth potential in emerging economies.

• Future Outlook: Innovations in formulations and expanding indications are critical for sustaining growth amidst intensifying competition. The market is projected to grow modestly, with a focus on technological advances and regional expansion.

• Investment & Development Strategy: Stakeholders should invest in research to develop patentable formulations and explore new indications, while leveraging geographic expansion opportunities.

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FAQs

1. What are the main formulations of clotrimazole currently available?
   Clotrimazole is primarily marketed as topical creams, ointments, powders, and vaginal suppositories, with ongoing research into novel delivery systems such as liposomal creams and transdermal patches.

2. Are there any efforts to develop systemic formulations of clotrimazole?
   Systemic formulations are limited; existing research mainly explores topical applications. Some early-phase trials are investigating oral or intravaginal formulations for specialized indications, but these are not yet commercially mature.

3. How does the rise of antifungal resistance impact clotrimazole’s efficacy?
   While resistance to clotrimazole remains rare, reports have emerged, underscoring the importance of appropriate use. Continuous surveillance and the development of combination therapies are strategies to address potential resistance issues.

4. What competitive advantages does clotrimazole have over newer antifungals?
   Its longstanding clinical safety, affordability, widespread availability, and extensive clinical experience underpin its competitive edge, although newer agents may offer advantages like improved pharmacokinetics or broader spectrum activity.

5. What is the outlook for clotrimazole in the digital health era?
   Integration with telemedicine platforms and digital health tools can facilitate patient education, adherence, and remote monitoring, enhancing treatment outcomes and expanding market reach.

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Sources:

[1] ClinicalTrials.gov. "Clotrimazole Trials."
[2] MarketsandMarkets. "Antifungal Drugs Market."
[3] GlobalData. "Pharmaceutical Industry Reports."
[4] European Medicines Agency. "Clotrimazole Summary of Product Characteristics."
[5] IDSA. "Clinical Practice Guidelines for the Treatment of Candidiasis."