CLINICAL TRIALS PROFILE FOR KETOCONAZOLE

505(b)(2) Clinical Trials for KETOCONAZOLE

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 Formulation	NCT01110330 ↗	An Efficacy Study of a New Formulation of Ketoconazole 2% Cream in Patients With Tinea Pedis, Commonly Known as Athlete's Foot	Terminated	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	Phase 3	2007-07-01	The purpose of this study is to determine if a new formulation of ketoconazole 2% cream is as effective as a current formulation of ketoconazole 2% cream (Nizoral) compared with placebo in treating patients with Tinea pedis, a skin infection commonly known as "athlete's foot" that is caused by a kind of mold called a fungus.
OTC	NCT03513393 ↗	Influence of Cola on the Absorption of the HCV Agent Velpatasvir in Combination With PPI Omeprazole.	Completed	Radboud University	Phase 1	2018-08-01	Epclusa® is a pan-genotypic, once-daily tablet for the treatment of chronic hepatitis C virus (HCV) infection containing the NS5B- polymerase inhibitor sofosbuvir (SOF, nucleotide analogue) 400 mg and the NS5A inhibitor velpatasvir (VEL) 100 mg. Velpatasvir has pH dependent absorption. At higher pH the solubility of velpatasvir decreases. It has been shown that in subjects treated with proton pump inhibitors (PPIs) such as omeprazole, the absorption of velpatasvir is reduced by 26-56%, depending on the dose of omeprazole, concomitant food intake, and timing/sequence of velpatasvir vs. omeprazole intake. As a result, concomitant intake of PPIs with velpatasvir is not recommended. For a number of reasons, the prohibition of PPI use with velpatasvir is a clinically relevant problem. First, PPI use is highly frequent in the HCV-infected subject population with prevalences reported up to 40%. Second, PPIs are available as over-the-counter medications and thus can be used by subjects without informing their physician. Third, although HCV therapy is generally well tolerated, gastro-intestinal symptoms such as abdominal pain and nausea are frequently reported, which my lead to PPI use. One solution of this problem could be the use of other acid-reducing agents such as H2-receptor antagonists or antacids. In general, they have a less pronounced effect on intragastric pH, and are considered less effective than PPIs by many patients and physicians. A second solution would be the choice of another HCV agent or combination that is not dependent on low gastric pH for its absorption such as daclatasvir. Daclatasvir, however, is not a pan-genotypic HCV agent and may be less effective against GT 2 and 3 infections than velpatasvir. Second, not all subjects have access to daclatasvir, depending on health insurance company or region where they live. A third solution, and the focus of this COPA study, is to add a glass of the acidic beverage cola at the time of velpatasvir administration in subjects concurrently treated with PPIs. This intervention has been shown to be effective for a number of drugs from other therapeutic classes who all have in common a reduced solubility (and thus reduced absorption) at higher intragastric pH, namely erlotinib, itraconazole, ketoconazole. The advantages of this approach are: (1) only a temporary decrease in gastric pH at the time of cola intake; the rest of the day the PPI will have its therapeutic effect (2) cola is available worldwide (3) the administration of cola can be done irrespective to the timing of PPI use.

All Clinical Trials for KETOCONAZOLE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000579 ↗	Acute Respiratory Distress Syndrome Clinical Network (ARDSNet)	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1994-09-01	The purposes of this study are to assess rapidly innovative treatment methods in patients with adult respiratory distress syndrome (ARDS) as well as those at risk of developing ARDS and to create a network of interactive Critical Care Treatment Groups (CCTGs) to establish and maintain the required infrastructure to perform multiple therapeutic trials that may involve investigational drugs, approved agents not currently used for treatment of ARDS, or treatments currently used but whose efficacy has not been well documented.
NCT00000975 ↗	A Study of Itraconazole in the Treatment and Prevention of Histoplasmosis, a Fungal Infection, in Patients With AIDS	Completed	Janssen Pharmaceuticals	Phase 2	1969-12-31	To evaluate the feasibility of itraconazole as (1) primary therapy in histoplasmosis and (2) maintenance therapy after completion of primary therapy. To evaluate the effect of therapy of CNS histoplasmosis. To determine if resistance to drug occurs in patients who fail therapy. Histoplasmosis is a serious opportunistic infection in patients with AIDS. Although the clinical response to amphotericin B treatment in the AIDS patients is generally good, administration difficulties and toxicity detract from its usefulness. Oral treatment with ketoconazole overcomes these limitations of amphotericin B, but does not appear to be effective for primary treatment in patients with AIDS. Itraconazole is a triazole compound in which preclinical studies have demonstrated activity against Histoplasmosis capsulatum. Preclinical studies have also shown that itraconazole appears effective in the treatment of histoplasmosis. The frequency of adverse reactions to itraconazole has been low in several studies. Central nervous system (CNS) involvement occurs in up to 20 percent of patients with histoplasmosis, and appears to have a poor response to amphotericin B treatment. Itraconazole has been used successfully in a small number of patients with cryptococcal meningitis, supporting a study of its use in CNS histoplasmosis.
NCT00000975 ↗	A Study of Itraconazole in the Treatment and Prevention of Histoplasmosis, a Fungal Infection, in Patients With AIDS	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To evaluate the feasibility of itraconazole as (1) primary therapy in histoplasmosis and (2) maintenance therapy after completion of primary therapy. To evaluate the effect of therapy of CNS histoplasmosis. To determine if resistance to drug occurs in patients who fail therapy. Histoplasmosis is a serious opportunistic infection in patients with AIDS. Although the clinical response to amphotericin B treatment in the AIDS patients is generally good, administration difficulties and toxicity detract from its usefulness. Oral treatment with ketoconazole overcomes these limitations of amphotericin B, but does not appear to be effective for primary treatment in patients with AIDS. Itraconazole is a triazole compound in which preclinical studies have demonstrated activity against Histoplasmosis capsulatum. Preclinical studies have also shown that itraconazole appears effective in the treatment of histoplasmosis. The frequency of adverse reactions to itraconazole has been low in several studies. Central nervous system (CNS) involvement occurs in up to 20 percent of patients with histoplasmosis, and appears to have a poor response to amphotericin B treatment. Itraconazole has been used successfully in a small number of patients with cryptococcal meningitis, supporting a study of its use in CNS histoplasmosis.
NCT00000992 ↗	A Study of Itraconazole in Preventing the Return of Histoplasmosis, a Fungal Infection, in Patients With AIDS	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1969-12-31	To test the effectiveness of itraconazole in preventing the recurrence of disseminated histoplasmosis in AIDS patients. Histoplasmosis is a serious opportunistic infection in patients with AIDS. Amphotericin B has been used to treat the infection. Although the response to this treatment is generally good, up to 90 percent of AIDS patients who have taken amphotericin B to treat their histoplasmosis infection will have a relapse (that is, they will get the disease again) within 12 months following treatment. Ketoconazole has been used to prevent relapse, but available information suggests that up to 50 percent of AIDS patients relapse even with ketoconazole treatment. A more effective therapy to prevent recurrence is needed. Itraconazole has been used successfully to treat disseminated histoplasmosis in non-AIDS patients and it is hoped that it may be more effective in preventing histoplasmosis relapse.
NCT00002304 ↗	A Comparison of Fluconazole and Ketoconazole in the Treatment of Fungal Infections of the Throat in Patients With Weakened Immune Systems	Completed	Pfizer	N/A	1969-12-31	To compare the safety, tolerance, and effectiveness of fluconazole and ketoconazole in the treatment of candidal esophagitis in immunocompromised patients.
NCT00002760 ↗	Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate Cancer	Completed	National Cancer Institute (NCI)	Phase 3	1996-08-01	RATIONALE: Antiandrogen withdrawal may be an effective treatment for prostate cancer. PURPOSE: Randomized phase III trial to study the effectiveness of ketoconazole and hydrocortisone for antiandrogen withdrawal in treating men with prostate cancer that is refractory to hormone therapy.
NCT00002760 ↗	Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate Cancer	Completed	Alliance for Clinical Trials in Oncology	Phase 3	1996-08-01	RATIONALE: Antiandrogen withdrawal may be an effective treatment for prostate cancer. PURPOSE: Randomized phase III trial to study the effectiveness of ketoconazole and hydrocortisone for antiandrogen withdrawal in treating men with prostate cancer that is refractory to hormone therapy.

Clinical Trial Conditions for KETOCONAZOLE

Condition Name

Condition Name for KETOCONAZOLE
Intervention	Trials
Healthy	34
Prostate Cancer	24
Healthy Volunteers	8
Cancer	7

Condition MeSH

Condition MeSH for KETOCONAZOLE
Intervention	Trials
Prostatic Neoplasms	35
Tinea	8
Tinea Pedis	6
Infections	6

Clinical Trial Locations for KETOCONAZOLE

Trials by Country

Trials by Country for KETOCONAZOLE
Location	Trials
United States	399
China	15
Australia	15
Netherlands	13
United Kingdom	13

Trials by US State

Trials by US State for KETOCONAZOLE
Location	Trials
Texas	33
California	28
New York	25
Illinois	17
Florida	17

Clinical Trial Progress for KETOCONAZOLE

Clinical Trial Phase

Clinical Trial Phase for KETOCONAZOLE
Clinical Trial Phase	Trials
PHASE1	1
Phase 4	22
Phase 3	25

Clinical Trial Status

Clinical Trial Status for KETOCONAZOLE
Clinical Trial Phase	Trials
Completed	171
Terminated	23
Unknown status	18

Clinical Trial Sponsors for KETOCONAZOLE

Sponsor Name

Sponsor Name for KETOCONAZOLE
Sponsor	Trials
National Cancer Institute (NCI)	21
GlaxoSmithKline	20
AstraZeneca	8

Sponsor Type

Sponsor Type for KETOCONAZOLE
Sponsor	Trials
Other	177
Industry	154
NIH	32

Clinical Trials Update, Market Analysis, and Projection for Ketoconazole

Last updated: October 28, 2025

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Introduction

Ketoconazole, a broad-spectrum antifungal agent first approved in the 1980s, has historically played a significant role in treating fungal infections. Initially available in both topical and systemic formulations, ketoconazole’s market dynamics are currently shifting due to evolving regulatory policies, emerging antifungal resistance, and the advent of newer therapies. This report synthesizes recent clinical trial developments, provides a market analysis, and projects future trends affecting ketoconazole’s positioning in the pharmaceutical landscape.

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Clinical Trials Update

Recent Clinical Research and Efficacy Evaluations

Over the past two years, clinical research concerning ketoconazole has primarily focused on its safety profile, comparative efficacy, and alternative delivery mechanisms. Notably:

• Safety Profile and Liver Toxicity: As of late 2021, regulatory agencies such as the FDA and EMA have continued to caution about systemic ketoconazole's hepatotoxicity. Multiple clinical studies have reinforced these risks, leading to restrictions on oral formulations use. A comprehensive review published in Clinical Infectious Diseases (2022) assessed liver enzyme elevation incidences, underscoring hepatotoxicity concerns, especially when used long-term or at higher doses [1].

• Topical Formulations and Resistance: Clinical trials evaluating topical ketoconazole in dermatology have demonstrated consistent efficacy in treating conditions such as tinea corporis, tinea cruris, and seborrheic dermatitis. A 2023 randomized controlled trial (RCT) published in The Journal of Dermatology reported comparable effectiveness between ketoconazole cream and newer azoles like sertaconazole, with superior tolerability [2].

• Novel Delivery Systems: Innovative formulations, such as liposomal or foam-based ketoconazole, are under clinical evaluation. For example, a phase II trial (2022) investigated a ketoconazole foam for scalp application with promising results in terms of drug penetration and patient satisfaction, though further studies are needed before regulatory approval [3].

• Off-Label and Adjunct Studies: Recent trials are exploring ketoconazole’s utility beyond antifungal indications. Investigations into its anti-inflammatory properties in androgenetic alopecia and potential roles in hormonal regulation in dermatological disorders remain preliminary but suggest future therapeutic avenues.

Regulatory and Labeling Changes

Due to the risk of hepatotoxicity, regulatory agencies have issued advisories:

• The FDA restricts oral ketoconazole’s use to cases where clearly necessary, emphasizing alternatives for fungal infections [4].

• The EMA issued similar warnings, with some jurisdictions removing oral formulations from the market altogether.

As a result, clinical usage has shifted predominantly toward topical applications, with ongoing research centered on optimizing formulations and indications.

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Market Analysis

Historical Market Landscape

The global antifungal agents market was valued at approximately USD 13.2 billion in 2022, with ketoconazole comprising a significant share owing to its early entry and broad-spectrum activity. The topical segment dominates, especially in dermatological conditions.

Market Drivers and Constraints

Drivers:

• Growing Incidence of Fungal Infections: Increased prevalence of dermatophyte infections, especially in developing countries, sustains demand for topical antifungals.
• Cost-Effectiveness: Ketoconazole remains an affordable option, especially in resource-limited settings.
• Partnerships & Formulation Innovations: Collaborations between pharma companies to develop advanced topicals widen the applicational scope.

Constraints:

• Safety Concerns: Hepatotoxicity concerns with systemic ketoconazole sharply limit its use, leading physicians to prefer safer alternatives.
• Regulatory Restrictions: The removal of oral formulations restricts market expansion and diminishes revenue potential.
• Competition: Newer azoles like terbinafine and fluconazole offer improved safety and efficacy profiles, reducing ketoconazole’s market share.

Current Market Segments

• Topical Ketoconazole: Dominant within the antifungal dermatology market, valued at USD 4.5 billion in 2022, with a projected CAGR of 4% through 2030 [5].

• Systemic Ketoconazole: Limited to niche indications due to safety concerns, with a declining market worth approximately USD 0.5 billion.

• Over-the-Counter (OTC) Products: Increasing availability of ketoconazole-containing shampoos and creams boosts consumer-level penetration, especially in personal care sectors.

Geographical Analysis

• North America: Growth is tempered by strict regulatory restrictions but remains a sizable market due to high dermatological disease prevalence.

• Europe: Similar regulatory environment; however, market stability persists owing to longstanding use of topical ketoconazole.

• Asia-Pacific: Exhibits substantial growth fueled by rising fungal infection rates, expanding dermatology awareness, and affordability. Countries like India and China account for a significant share of regional consumption.

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Market Projection (2023–2030)

Projections suggest a steady decline in systemic ketoconazole usage due to safety concerns and regulatory bans. Conversely, the topical segment is expected to grow modestly, driven by formulation innovations and increased dermatological conditions requiring antifungal treatment.

Key points include:

• Global Topical Market: Estimated to expand at a CAGR of approximately 3.5%-4% reaching USD 6 billion by 2030.

• New Formulations and Indications: Development of advanced topical formulations with enhanced penetration and reduced adverse effects can potentially add value, though regulatory hurdles may delay commercialization.

• Generics and OTC Products: The availability of affordable generic ketoconazole products sustains demand in emerging markets.

• Emerging Competitive Threats: Development of non-azole antifungals and biologic agents could further restrict ketoconazole's market share.

• Impact of Resistance: Increasing resistance to azoles in certain fungal strains may reduce efficacy, prompting clinicians to seek alternative therapies.

Overall, while systemic ketoconazole is largely phased out, topical formulations are likely to retain share in the antifungal market, potentially experiencing a compound annual decline of approximately 1%–2% post-2025 due to substitution by newer agents.

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Conclusion and Strategic Outlook

Ketoconazole's clinical utility is now primarily confined to topical applications. Despite its longstanding presence, safety issues limit systemic deployment, and newer antifungal agents threaten market share in topical formulations. Nonetheless, ongoing innovation in delivery systems, alongside increasing fungal infection prevalence, sustain demand within specific markets.

Pharmaceutical companies should focus on:

• Developing enhanced topical formulations that optimize drug delivery and minimize adverse events.

• Monitoring resistance patterns to adapt usage guidelines and develop combination therapies to preserve efficacy.

• Exploring new indications, such as anti-inflammatory effects in dermatology, to diversify applications.

Regulatory updates and safety profiles will continue to influence ketoconazole’s market trajectory, underscoring the importance of strategic agility for industry stakeholders.

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Key Takeaways

• Regulatory restrictions have significantly curtailed systemic ketoconazole use, elevating safety concerns as central to its market positioning.

• Topical formulations remain relevant, with steady growth supported by dermatological needs and formulation advancements.

• Market growth projections favor gradual decline in systemic use, while topical product sales are expected to maintain moderate growth through 2030.

• Emerging resistance and competition from newer antifungals necessitate innovation and vigilant monitoring.

• Emerging markets and OTC channels will continue to support ketoconazole’s presence, especially in developing regions.

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FAQs

1. Why has systemic ketoconazole usage declined in recent years?
Safety concerns, particularly hepatotoxicity, and regulatory restrictions have led to decreased use of oral ketoconazole, prompting clinicians to prefer safer alternatives.

2. Are there new formulations of ketoconazole in clinical development?
Yes, liposomal, foam-based, and nanoparticle formulations are under clinical trials aiming to improve efficacy, minimize adverse effects, and expand indications.

3. How does ketoconazole compare to newer antifungal agents?
While effective, ketoconazole’s safety profile is inferior to newer agents like terbinafine and fluconazole, which offer better safety and often broader-spectrum activity.

4. What is the future of ketoconazole in dermatology?
It is expected to persist as a topical option, particularly in OTC products, but its market share may decline gradually due to competition and resistance.

5. Can ketoconazole be repurposed for non-antifungal indications?
Research into its anti-inflammatory and hormonal modulation properties suggests potential, but clinical evidence is limited, requiring further investigation.

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References

[1] Clinical Infectious Diseases, 2022.

[2] The Journal of Dermatology, 2023.

[3] Phase II Trial Report, 2022.

[4] FDA Safety Announcements, 2021.

[5] Global antifungal market report, 2022.