CLINICAL TRIALS PROFILE FOR FLUCONAZOLE

505(b)(2) Clinical Trials for FLUCONAZOLE

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 Dosage	NCT02372357 ↗	A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area	Completed	Institutul Clinic Fundeni	Phase 4	2012-02-01	A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.
New Dosage	NCT02372357 ↗	A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area	Completed	Institutul Clinic Fundeni Bucharest	Phase 4	2012-02-01	A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.
New Dosage	NCT02372357 ↗	A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area	Completed	Universitaire Ziekenhuizen Leuven	Phase 4	2012-02-01	A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.
New Indication	NCT04495608 ↗	Fluconazole in Hypercalciuric Patients With Increased 1,25(OH)2D Levels	Recruiting	Hospices Civils de Lyon	Phase 2	2021-01-13	Hypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis leading to Chronic Kidney Disease (CKD) and bone complications in adults. Hypercalciuria can be secondary to increased intestinal absorption and/or increased renal distal tubular reabsorption of calcium due to increased active vitamin D, i.e. 1,25(OH)2D, levels. The management of hypercalciuria is challenging. Classic management based on hyperhydration and dietary advice has low impact on calciuria and therefore on CKD progression. Other strategies such as hydrochlorothiazide can be proposed, however with an uncertain medical benefit in view of side effects (hypokalemia, asthenia, potential cutaneous long-term side effects). Azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)2D levels. These antifungal drugs are commonly used in neonates, infants and adults; pharmacokinetic data are well described. Recently, to improve azoles tolerance, fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 mutation (1 adult) or NPTIIc mutations (1 child), while maintaining a stable renal function. Based on these observations, the investigators hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH)2D levels. The primary objective is to demonstrate that fluconazole normalizes or decreases calciuria after 4 months of treatment in patients with hypercalciuria and increased 1,25(OH)2D levels. The secondary objectives aim to describe: - the effects of fluconazole on the evolution over time of the calcium/phosphate metabolism, - the evolution of renal function, - the cohort at Baseline and after 4 months of treatment period, - the safety of fluconazole, - the onset of potential mycological resistances, - and the treatment compliance. This is a prospective, interventional, national, randomized in 2 parallel groups (1:1), controlled versus placebo, double blind trial. This study will involve patients between 10 and 50 years of age suffering from nephrolithiasis and/or nephrocalcinosis with hypercalciuria (> 0.1 mmol/kg/d) and increased 1,25 (OH)2D levels (≥ 150 pmol/l) and 25-OH-D levels (≥50 nmol/L). FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug (e.g. fluconazole) in rare renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients. If the results of this proof-of-concept randomized controlled trial are positive, the investigators will propose an extension phase to evaluate the long term efficacy and safety of fluconazole on renal and bone parameters.
OTC	NCT05059145 ↗	A Clinical Trial for Chlorhexidine as Treatment for Vulvovaginal Candidiasis	Not yet recruiting	Karolinska Institutet	Phase 2	2021-10-01	The overall aim of this study is to investigate if vaginally applied 1% chlorhexidine gluconate (CHG) could be an alternative treatment to oral fluconazole (FLZ), both during an acute episode and as prophylaxis, against recurrent infections of vulvovaginal candidiasis (RVVC). RVVC is very common in fertile women. Up to six months of treatment with FLZ is recommended for RVVC. Over the last ten years, the use of FLZ has increased markedly in many countries. No major problems have been noted with resistance development, but there is concern that this will occur in the future and alternative treatments are requested. In recent years, it has emerged that flukonazol interacts with several different types of drugs that are common in the patient group; several antidepressants, pain relief at dysmenorrhea (NSAID) and oral contraceptives to name a few. In Sweden an over-the-counter vaginal cream consisting of 1% chlorhexidine gluconate (Hibitane®) is available with the indication antiseptic use in vaginal examinations, especially during childbirth. The product has been used for a long time in various gynecological and obstetric surgical procedures. Hibitane® is approved during pregnancy and the cream is usually well tolerated. Our research group has previously done an in vitro study in which we analyzed the effect of FLZ and CHG's ability to kill fungal cells and to break down existing biofilm or prevent new biofilm formation. The biofilm formation is an important stage for the fungal cells to attach to surfaces such as skin and mucosa and is considered a first step in the development of an infection. In the biofilm, the fungus can hide from the immune system and also to some extent for various treatments aimed against the fungus. The results of the study showed that CHG was better than FLZ both at killing the fungal cells and preventing new biofilm from forming and dissolving already established "old" biofilm. This effect is absolutely crucial for successful treatment with antimycotics. These encouraging results form the basis of the planned study. If CHG is at least as effective as FLZ with little impact on vaginal lactobacillus, with high tolerability and without cytotoxic effect on epithelial cells, the results of the study might lead to major benefits to the patients with reduced risk of systemic side effects such as drug interactions, development of drug resistance and reduced drug costs.

All Clinical Trials for FLUCONAZOLE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000627 ↗	Pilot Study to Determine the Feasibility of Fluconazole for Induction Treatment and Suppression of Relapse of Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome	Completed	Pfizer	N/A	1969-12-31	To evaluate the use of fluconazole as (1) induction therapy in histoplasmosis, (2) maintenance therapy to prevent relapse of histoplasmosis. Histoplasmosis is a serious opportunistic infection in patients with AIDS. Fluconazole is a triazole antifungal agent that has been used successfully in the treatment of experimental histoplasmosis in animals, but has not been completely evaluated in patients for this use. It has been approved by the Food and Drug Administration for certain other fungal infections. Nevertheless, physicians are prescribing it to their patients with histoplasmosis. This is a pilot study to examine the role of fluconazole for treating histoplasmosis in AIDS patients.
NCT00000627 ↗	Pilot Study to Determine the Feasibility of Fluconazole for Induction Treatment and Suppression of Relapse of Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To evaluate the use of fluconazole as (1) induction therapy in histoplasmosis, (2) maintenance therapy to prevent relapse of histoplasmosis. Histoplasmosis is a serious opportunistic infection in patients with AIDS. Fluconazole is a triazole antifungal agent that has been used successfully in the treatment of experimental histoplasmosis in animals, but has not been completely evaluated in patients for this use. It has been approved by the Food and Drug Administration for certain other fungal infections. Nevertheless, physicians are prescribing it to their patients with histoplasmosis. This is a pilot study to examine the role of fluconazole for treating histoplasmosis in AIDS patients.
NCT00000639 ↗	A Randomized Double Blind Protocol Comparing Amphotericin B With Flucytosine to Amphotericin B Alone Followed by a Comparison of Fluconazole and Itraconazole in the Treatment of Acute Cryptococcal Meningitis	Completed	Washington University School of Medicine	N/A	1969-12-31	To evaluate the effectiveness and safety of amphotericin B plus flucytosine (5-fluorocytosine) compared to amphotericin B alone for a first episode of acute cryptococcal meningitis in AIDS patients, and to compare the effectiveness and safety of fluconazole versus itraconazole. At least 10 percent of patients with a low CD4 count and HIV infection will develop meningitis due to Cryptococcus neoformans. More effective treatments than the standard therapy need to be explored.
NCT00000639 ↗	A Randomized Double Blind Protocol Comparing Amphotericin B With Flucytosine to Amphotericin B Alone Followed by a Comparison of Fluconazole and Itraconazole in the Treatment of Acute Cryptococcal Meningitis	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To evaluate the effectiveness and safety of amphotericin B plus flucytosine (5-fluorocytosine) compared to amphotericin B alone for a first episode of acute cryptococcal meningitis in AIDS patients, and to compare the effectiveness and safety of fluconazole versus itraconazole. At least 10 percent of patients with a low CD4 count and HIV infection will develop meningitis due to Cryptococcus neoformans. More effective treatments than the standard therapy need to be explored.
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.
NCT00000708 ↗	Multi-center Comparison of Fluconazole (UK-49,858) and Amphotericin B as Treatment for Acute Cryptococcal Meningitis	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To compare the safety and effectiveness of fluconazole (FCZ) and amphotericin B (AMB), alone or in combination with flucytosine (FLC), as treatment for acute cryptococcal meningitis in patients who have not been treated previously or who have relapsed after a previous successful treatment. Cryptococcal meningitis is an important cause of disease and death among patients with AIDS. Usually AMB is given either alone or with FLC to patients with this infection, but these treatments are not always effective and both have toxic effects. Animal studies and preliminary studies in humans show that FCZ is active in cryptococcal meningitis and suggest that it may be less toxic than either AMB or FLC.

Clinical Trial Conditions for FLUCONAZOLE

Condition Name

Condition Name for FLUCONAZOLE
Intervention	Trials
HIV Infections	42
Candidiasis	21
Mycoses	19
Meningitis, Cryptococcal	16

Condition MeSH

Condition MeSH for FLUCONAZOLE
Intervention	Trials
Candidiasis	77
Mycoses	45
HIV Infections	45
Infections	31

Clinical Trial Locations for FLUCONAZOLE

Trials by Country

Trials by Country for FLUCONAZOLE
Location	Trials
United States	771
China	35
Canada	28
Spain	20
Belgium	15

Trials by US State

Trials by US State for FLUCONAZOLE
Location	Trials
California	57
Texas	55
New York	46
Florida	46
Pennsylvania	40

Clinical Trial Progress for FLUCONAZOLE

Clinical Trial Phase

Clinical Trial Phase for FLUCONAZOLE
Clinical Trial Phase	Trials
PHASE4	5
PHASE3	3
PHASE2	4

Clinical Trial Status

Clinical Trial Status for FLUCONAZOLE
Clinical Trial Phase	Trials
Completed	189
Recruiting	27
Unknown status	21

Clinical Trial Sponsors for FLUCONAZOLE

Sponsor Name

Sponsor Name for FLUCONAZOLE
Sponsor	Trials
Pfizer	40
National Institute of Allergy and Infectious Diseases (NIAID)	25
Merck Sharp & Dohme Corp.	7

Sponsor Type

Sponsor Type for FLUCONAZOLE
Sponsor	Trials
Other	227
Industry	167
NIH	46

Fluconazole: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 26, 2025

Introduction

Fluconazole, a triazole antifungal agent, has been a cornerstone in the management of various fungal infections since its approval by the FDA in 1990. Its broad-spectrum efficacy against Candida species, Cryptococcus neoformans, and other fungi has cemented its place in infectious disease pharmacotherapy. As the landscape of antifungal treatment evolves amidst rising resistance and innovative therapies, it is imperative to analyze recent clinical developments, market dynamics, and future growth prospects for fluconazole.

Clinical Trials Update

Current and Recent Clinical Trials

In recent years, numerous clinical trials have examined fluconazole's efficacy, safety profile, and potential new indications. The focus has notably shifted toward personalized medicine, resistance management, and combination therapies.

• Antifungal Resistance and Susceptibility: Multiple studies have investigated fluconazole's diminishing efficacy against non-albicans Candida species and resistant strains. For example, a 2022 multicenter trial published in Mycoses assessed the susceptibility patterns of Candida isolates and confirmed rising resistance trends, especially among Candida glabrata and Candida krusei [1].

• Prophylactic Use in Immunocompromised Patients: Ongoing trials, including a phase III study on fluconazole prophylaxis in hematological malignancies, evaluate its effectiveness in reducing invasive fungal infections (IFIs). Preliminary results suggest sustained efficacy but raise concerns over resistance development.

• Combination Therapy Trials: Recent clinical investigations probe fluconazole in combination with immunomodulators or other antifungals, such as echinocandins, to combat resistant infections. For instance, a 2021 trial in Antimicrobial Agents and Chemotherapy evaluated fluconazole combined with caspofungin, revealing promising synergistic effects against resistant strains [2].

• Alternative Routes and Dosing Strategies: Trials exploring oral versus intravenous administration, and modified dosing protocols, aim to optimize therapeutic outcomes while minimizing adverse effects.

Emerging Data and Gaps

While fluconazole remains standard, the emergence of resistant strains and adverse event profiles necessitate ongoing evaluation. Recent trials underscore the importance of antifungal stewardship and susceptibility-guided therapy to preserve efficacy.

Market Analysis

Global Market Overview

The global antifungal market, valued at approximately USD 13.5 billion in 2022, is projected to grow at a CAGR of around 4.8% through 2030 [3]. Fluconazole dominates this segment with an estimated share exceeding 40%, attributed to its affordability, well-established safety record, and extensive clinical use.

Key Market Drivers

• Rising Incidence of Fungal Infections: Increasing cases of immunosuppression due to HIV, cancer, organ transplantation, and diabetes amplify demand for antifungals, especially fluconazole.

• Healthcare Infrastructure Expansion: Developing economies expanding healthcare access are contributing to increased prescription volumes.

• Generic Competition and Pricing: The availability of multiple generic formulations has made fluconazole an accessible option in both developed and emerging markets.

Market Challenges

• Resistance Trends: The growing resistance among non-albicans Candida species threatens prolonged efficacy. This resistance trend could constrain market growth if alternative therapies gain favor.

• Emerging Alternatives: Potent new antifungals like ibrexafungerp and novel azoles, such as isavuconazole, are gaining market share due to improved safety and resistance profiles.

Regional Insights

• North America: The largest market share, driven by high healthcare expenditure, advanced diagnostic capabilities, and prevalent invasive fungal infections.

• Europe: Steady growth, with stringent regulatory pathways favoring established drugs like fluconazole.

• Asia-Pacific: The fastest-growing region, fueled by expanding healthcare infrastructure, rising fungal disease burden, and affordability of generics.

Future Market Projections

Market Growth Trajectory

Given the current trends, the fluconazole market is expected to maintain moderate growth, tailored by resistance management strategies and emerging treatment alternatives.

• Forecast to 2030: Projected cumulative growth in the fluconazole segment is approximately 4.5% annually, driven primarily by emerging resistance in certain Candida species, requiring vigilant monitoring.

Opportunities and Innovation

• Development of Resistance-Resilient Formulations: Formulations with enhanced stability and targeted delivery may extend fluconazole's utility.

• Biomarker-Guided Therapy: Advances in diagnostic technology enabling rapid susceptibility testing could optimize use and reduce resistance development.

• Combo-therapy Approaches: Incorporating fluconazole in combination regimens may preserve its clinical relevance.

Potential Disruptors

• New Antifungal Agents: Molecules with novel mechanisms of action are poised to challenge fluconazole's dominance, especially in resistant infections.

• Regulatory and Funding Shifts: Changes in healthcare policy and funding priorities towards novel therapies could impact market size.

Conclusion

Fluconazole remains a pivotal antifungal agent, underpinned by extensive clinical experience and a robust market presence. However, emerging resistance and the advent of novel therapies necessitate adaptive clinical and commercial strategies. Continuous monitoring of clinical trial outcomes, resistance patterns, and market shifts will be critical for stakeholders aiming to optimize the therapeutic value and commercial viability of fluconazole.

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Key Takeaways

• Clinical Development: Ongoing trials focus on resistance management, combination treatments, and optimized dosing, underscoring the need for vigilant antifungal stewardship.

• Market Dynamics: Despite challenges, fluconazole maintains a dominant position due to cost-effectiveness and established efficacy, primarily in North America and Asia-Pacific regions.

• Growth Factors: Rising fungal infection prevalence and expanding healthcare infrastructure support continued demand, though resistance issues and competition temper growth prospects.

• Future Outlook: The market will evolve with technological advances in diagnostics, formulation improvements, and potential combination therapies, maintaining fluconazole’s relevance amid emerging antifungal options.

• Strategic Focus: Pharmaceutical companies must invest in resistance surveillance, support stewardship programs, and explore innovative formulations to sustain fluconazole's market presence.

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FAQs

1. How is resistance affecting fluconazole’s clinical effectiveness?
Resistance, particularly among non-albicans Candida species like C. glabrata and C. krusei, is diminishing fluconazole’s efficacy. Surveillance data highlights increasing resistance rates, prompting a shift toward alternative treatments in resistant infections.

2. Are there ongoing clinical trials for new indications of fluconazole?
Current trials primarily focus on optimizing existing uses, resistance management, and combination therapies. No major trials are investigating entirely new indications, but research into resistant invasive fungal infections is ongoing.

3. How does fluconazole compare with newer antifungals in terms of safety?
Fluconazole has a well-characterized safety profile, with relatively few serious adverse effects. Newer agents, like isavuconazole, may offer improved safety in specific populations but often at higher costs.

4. What are the major market regions driving fluconazole demand?
North America accounts for the largest share due to high healthcare expenditure, followed by Europe. Asia-Pacific exhibits rapid growth driven by expanding healthcare infrastructure and fungal disease prevalence.

5. What strategies can extend fluconazole’s market life?
Developing formulations resistant to resistance mechanisms, implementing biomarker-guided therapy, and combining fluconazole with other antifungals can sustain its clinical relevance and market share.

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Sources
[1] Mycoses, 2022, "Susceptibility patterns of Candida species in clinical isolates."
[2] Antimicrobial Agents and Chemotherapy, 2021, "Synergistic effects of fluconazole and caspofungin."
[3] MarketsandMarkets, 2023, "Antifungal Drugs Market by Type, Application, Region—Global Forecast to 2030."