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.

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	36
Canada	28
Spain	20
Belgium	15

Trials by US State

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

Clinical Trial Progress for fluconazole

Clinical Trial Phase

Clinical Trial Phase for fluconazole
Clinical Trial Phase	Trials
PHASE4	6
PHASE3	4
PHASE2	4

Clinical Trial Status

Clinical Trial Status for fluconazole
Clinical Trial Phase	Trials
Completed	189
Recruiting	28
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	231
Industry	168
NIH	46

Fluconazole Clinical Trials Update, Market Analysis, and Patent-Driven Generic/Biosimilar Outlook

Last updated: July 27, 2026

Fluconazole is a widely used triazole antifungal with mature clinical development history, broad global commercialization, and no biosimilar pathway. The competitive issue for market share is generic penetration and product-formulation lifecycle management (oral vs IV, dosing regimens, and managed-entry contracting), not biologic-type follow-on products. Current “clinical trials updates” are concentrated in niche settings (e.g., esophageal candidiasis, cryptococcal disease adjunct strategies, pediatric dosing, and antimicrobial resistance management) rather than new molecular entity (NME) registries.

What is the current clinical trial landscape for fluconazole?

Fluconazole trials over the past decade have largely focused on:

• Comparative efficacy/safety for specific indications (oral thrush, esophagitis, invasive candidiasis in limited protocols, and cryptococcal disease adjunct use).
• Dosing optimization in special populations (pediatrics, renal impairment).
• Formulation or regimen comparisons (step-down therapy, IV-to-oral switching, shorter-course strategies in superficial disease).
• Real-world evidence and resistance surveillance endpoints (species distribution, MIC trends, clinical response by Candida species).

Which fluconazole indications still see trial activity?

High-frequency “trial intent” clusters include:

• Esophageal candidiasis: oral vs IV strategies, step-down duration, and test-of-cure timing.
• Oropharyngeal candidiasis in HIV and immunocompromised populations: early clinical response and relapse rates.
• Vulvovaginal candidiasis: regimen equivalence, recurrence endpoints, and adherence outcomes.
• Cryptococcal disease: adjunct antifungal optimization, often in combination contexts (trial designs emphasize outcomes such as mortality and fungal clearance kinetics).

What endpoints are used most often in recent fluconazole studies?

• Mycological eradication at specified timepoints.
• Clinical response rates (symptom resolution, lesion healing, and relapse).
• Safety endpoints focused on liver enzymes, QT-related adverse events, and drug-drug interaction tolerability.
• Microbiology endpoints using standardized susceptibility breakpoints where available.

How big is the fluconazole market, and where does demand concentrate?

Fluconazole demand is driven by:

• Broad indication coverage across outpatient (thrush, vaginitis) and inpatient (esophagitis, complicated candidiasis) settings.
• Long-standing generics penetration that shifts the market from “drug discovery” to “volume, price, and contracting efficiency.”

What market segments matter for fluconazole revenue exposure?

By channel

• Hospital: IV and step-down pathways, infectious disease and oncology/nephrology formularies.
• Retail: OTC-like consumer pathways are limited in many jurisdictions, but pharmacy access and clinician prescribing drive oral use.

By patient segment

• Immunocompromised: oncology, transplant, HIV.
• Obstetric/gynecology: vulvovaginal candidiasis recurrence management.

By formulation

• Oral tablets/capsules and oral suspension remain the bulk of volume in many markets.
• IV fluconazole matters in hospitals and for patients needing parenteral therapy.

What is the generic and competitive landscape for fluconazole?

Fluconazole’s commercial reality is that most spend is captured by authorized generics and multiple unbranded or branded-generic offerings depending on the market. The competitive battleground is:

• Launch timing for each strength/formulation.
• Tenders and hospital formulary inclusion.
• Supply reliability and unit economics.
• Managed-entry and switching protocols.

How many generic products compete in major markets?

Fluconazole is widely generic in the US and EU, with many manufacturers across tablets/capsules and IV. In the US, Orange Book coverage is concentrated in older patents that have largely expired for many listed NDA/Nr products, shifting current disputes to device-like lifecycle changes (new NDCs, new strengths, new formulations) rather than core compound coverage.

When does fluconazole lose exclusivity, and what patents still matter?

Fluconazole has been commercial for decades, so compound-level exclusivity from early approvals has long ended. The remaining IP “hooks” are typically:

• Formulation or process patents for specific dosage forms (e.g., certain granulations, solid-state properties, IV presentation).
• Polymorph/state or stability patents for specific commercial presentations.
• Label or method-of-use patents, though these are less common for fluconazole given its mature indication set.

What do patent estates usually look like for fluconazole products today?

For many legacy antifungals like fluconazole, the estate profile in major jurisdictions often includes:

• Old compound patents fully expired.
• Later-filed formulation or manufacturing-process patents tied to particular NDCs or national applications.
• Limited new exclusivity from clinical protection since most indications are off-patent or not tied to new clinical data packages that extend exclusivity.

What is the Orange Book status of fluconazole in the United States?

In the US, fluconazole is marketed through multiple generic and reference listings. For most commercial presentations, the key practical point is that compound exclusivity has ended and most remaining protection is presentation-specific and likely expired or close to expiration.

What does this mean for FDA Paragraph IV risk?

• For mature generics, the probability of litigation over compound patents is low.
• When litigation occurs, it is usually tied to presentation-specific patents listed in the Orange Book (specific NDCs, strengths, dosage form changes, or stability/process claims).

Which companies are challenging fluconazole patents, and what litigation drives settlement behavior?

Because fluconazole is mature and generics are entrenched, litigation is less about creating entry barriers and more about:

• Resolving presentation-specific patent listings.
• Clearing the way for new NDC launches or strength/formulation changes.

The practical risk model for entrants is:

• Whether any Orange Book patents still remain in force for the specific NDC being pursued.
• Whether an active Paragraph IV case is pending for that NDC.

What formulations are protected for fluconazole, and how does that affect market entry?

In mature antifungal molecules, formulation IP typically affects:

• IV formulation stability and excipient systems.
• Oral dosage presentation characteristics (bioavailability targets, dissolution profiles).
• Manufacturing process steps that support shelf-life and consistency.

Oral vs IV: what changes the IP landscape?

• Oral formulations often face different process and stability claims than IV.
• IV products can have additional patent coverage tied to composition and sterility-related stability requirements, depending on the national and NDA/NDC history.

How does fluconazole compare with voriconazole, itraconazole, and posaconazole in clinical use and commercial dynamics?

Clinical positioning

• Fluconazole is often preferred for Candida infections where its spectrum and tissue distribution align with guidelines.
• Voriconazole and posaconazole are used for broader or more resistant fungal disease where fluconazole is less reliable due to species and resistance patterns.

Commercial positioning

• Fluconazole’s market is volume-driven due to generic affordability.
• Newer triazoles typically have more brand value and more constrained generic entry depending on patent lifecycles at the time of each molecule’s maturity.

What is the biosimilar risk for fluconazole?

There is no biosimilar risk. Fluconazole is a small-molecule antifungal. The relevant competitive categories are generics, authorized generics, and formulation-lifecycle changes.

What generic entry risks exist for fluconazole, and how can competitors mitigate them?

For a mature molecule, generic entry risks are mainly operational and regulatory:

• Patent clearance for specific NDCs if any late-listed formulation patents exist.
• Labeling and interchangeability issues tied to local guidelines (dose regimen accuracy, pediatric wording, renal dosing).
• Manufacturing process validation and stability data consistency to avoid product-quality setbacks that delay supply.

What does a launch timeline typically depend on?

• ANDA readiness for the targeted strength and dosage form.
• Bioequivalence study success for complex formulations or changes.
• Patent litigation timeline if any Orange Book patent remains listed for the intended NDC.

How might clinical evidence updates affect fluconazole prescribing?

Prescribing behavior in mature antifungals changes when:

• Guidelines update dosing duration and step-down strategies.
• New subgroup data indicates better outcomes in specific populations.
• Safety updates clarify hepatic monitoring, QT risk management, and interaction screening.

For fluconazole, the main “evidence impact” tends to be incremental rather than practice-transforming, because most clinicians already use it within established guideline frameworks.

Market projection for fluconazole: base case and drivers

Given maturity, fluconazole market trajectory usually follows:

• Flat-to-slight growth in absolute volume driven by infectious disease incidence and baseline fungal disease burden.
• Ongoing revenue pressure due to generic competition and periodic price resets.
• Growth supported by formulary standardization where clinical efficacy remains guideline-consistent.

Key growth or decline drivers to monitor

Demand drivers

• High-risk immunocompromised populations (oncology, transplant, HIV).
• Hospital protocol adoption for antifungal stewardship (fluconazole step-down pathways).

Supply and pricing drivers

• Competitive entry waves for each formulation/strength.
• Tender price compression.
• Supply disruptions that briefly lift spot pricing.

Projection style that fits the market

A realistic projection framework for fluconazole is:

• Track by geography: US, EU5, UK, and select APAC markets where pricing dynamics differ.
• Track by formulation: oral vs IV.
• Track by payer contracting: hospital tender cycles often dominate.

Key Takeaways

• Fluconazole is mature with no biosimilar pathway; competition is generic and formulation lifecycle driven.
• Clinical trial activity is concentrated in regimen optimization, special populations, and indication-specific performance endpoints, not new compound development.
• Market outcomes hinge on pricing and contracting, not patent expiration of the parent molecule.
• Remaining IP, if any, is usually NDC-specific (formulation/process) and affects entry logistics rather than compound-level exclusivity.

FAQs

1. What are the most common recent clinical endpoints in fluconazole studies?
   Mycological eradication, clinical response at test-of-cure, relapse rates, and safety including hepatic enzymes and QT-related risk.

2. Does fluconazole have any biosimilar competitors?
   No. Fluconazole is a small-molecule drug, so competition is from generics and authorized generics.

3. What patient groups drive fluconazole demand most?
   Immunocompromised patients, including oncology/transplant populations and patients with HIV, plus outpatient vulvovaginal and oropharyngeal candidiasis cohorts.

4. How do formulation differences (oral vs IV) affect generic approval and market entry?
   They can change the relevant patent lists, bioequivalence expectations, and stability/process validation needs for specific NDCs.

5. What is the biggest risk for a new generic entrant of fluconazole?
   Patent clearance for the specific strength/dosage form being pursued plus bioequivalence and manufacturing consistency for that formulation.

References

1. FDA. Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book). US Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm
2. ClinicalTrials.gov. Fluconazole trials. U.S. National Library of Medicine. https://clinicaltrials.gov/