#1 Clinical Trials Search in Europe

CICLOPIROX

Ciclopirox is a synthetic antifungal medication that has been the subject of numerous clinical trials exploring its effectiveness in treating various conditions. While primarily known as an antifungal agent used in topical formulations for skin and nail infections, researchers are also investigating ciclopirox for potential uses in more serious conditions like cancer and blood disorders. This article examines the current landscape of clinical trials involving ciclopirox, highlighting its various applications, formulations, and the ongoing research to expand its therapeutic potential beyond traditional antifungal uses.

Table of Contents

What is Ciclopirox?

Ciclopirox (also known as ciclopirox olamine) is a broad-spectrum antifungal medication used to treat various fungal infections. It is available in several forms including cream, lotion, nail lacquer, topical suspension, and shampoo. In some research settings, it’s also being tested as an oral medication for new therapeutic uses beyond its traditional antifungal applications.[1]

Ciclopirox is sold under various brand names depending on the country and formulation, including Penlac, Loprox, Ciclochem, and Mycoster. Each formulation is designed to treat specific types of fungal infections in different parts of the body.[2]

How Ciclopirox Works

Ciclopirox has a unique mechanism of action compared to other antifungal medications. It works through multiple pathways:

  • It has fungicidal activity (kills fungi) by inhibiting the cellular uptake of essential substances needed for fungal metabolism and growth
  • It binds irreversibly with cell structures such as mitochondria, ribosomes, microsomes, and cell walls
  • Unlike many other antifungals that target ergosterol in fungal cell membranes, ciclopirox interferes with various cellular processes

This comprehensive mechanism makes ciclopirox effective against a wide range of organisms, including dermatophytes (fungi that cause skin infections), yeasts, molds, actinomycetes, and some bacteria.[2]

Available Formulations

Ciclopirox is available in several formulations, each designed for specific conditions:

  • Nail lacquer (8%) – for treating onychomycosis (nail fungus)
  • Cream (0.77%) – for treating tinea pedis (athlete’s foot) and other skin fungal infections
  • Topical suspension (0.77%) – alternative to cream for certain skin conditions
  • Shampoo (1%) – for treating seborrheic dermatitis of the scalp and tinea capitis
  • Oral solution – currently being investigated for new uses in clinical trials

The appropriate formulation depends on the type and location of the fungal infection being treated.[4][5]

Treatment of Fungal Infections

Onychomycosis (Nail Fungus)

Ciclopirox 8% nail lacquer (sometimes marketed as Penlac) is an established treatment for onychomycosis, a fungal infection affecting the nails. It’s particularly useful for mild to moderate cases of distal subungual onychomycosis (DSO), which affects the nail bed and underside of the nail plate.[4]

The application regimen typically involves:

  • Daily application to affected nails
  • Filing down infected nails before application
  • Applying to the entire nail surface including under the nail tip
  • Treatment generally continues for several months (up to 48 weeks) as nail fungi are persistent and nails grow slowly

Complete cure rates (both mycological cure and visual improvement) vary but are higher when ciclopirox is used consistently over the recommended period. Some studies evaluate a treatment called “complete cure,” which means both the elimination of fungi (confirmed by laboratory testing) and the visual appearance of a healthy nail.[14]

Ciclopirox nail lacquer has also been studied in children with onychomycosis, with research suggesting it may have comparable efficacy to systemic (oral) therapy with a better safety profile and lower cost.[4]

Tinea Pedis (Athlete’s Foot)

For tinea pedis (athlete’s foot), ciclopirox is available as a cream or topical suspension at a 0.77% concentration. Clinical studies have shown that ciclopirox is effective in treating this common fungal foot infection.[5][7]

Treatment success for tinea pedis with ciclopirox requires:

  • Regular application as directed (typically twice daily)
  • Continuing treatment for the full prescribed period, even if symptoms improve
  • Following proper foot hygiene practices alongside medication use

Studies comparing generic ciclopirox topical formulations with reference (brand name) products have shown comparable safety and efficacy profiles in treating tinea pedis.[5]

Dermatomycoses in Children

Ciclopirox has been studied for treating dermatomycoses (fungal skin infections) in children as young as 3 months old. A Phase IV study evaluated ciclopirox olamine cream in children aged 3 months to 10 years with various types of dermatomycoses.[2]

The study found that:

  • Ciclopirox cream was applied twice daily for 28 days
  • The treatment showed good efficacy and safety profile
  • Follow-up continued for four weeks after treatment to evaluate the relapse rate

This research is important because there were limited previous data on ciclopirox use in children under 10 years of age. The study provided evidence for both the safety and effectiveness of ciclopirox cream formulation in treating fungal skin infections in pediatric patients.[2]

Tinea Capitis (Scalp Ringworm)

Ciclopirox 1% shampoo has been studied as an adjunctive treatment for tinea capitis (scalp ringworm) in children. While oral antifungal medication (typically griseofulvin) is the primary treatment for tinea capitis, antifungal shampoos can help reduce the time to cure and potentially prevent recurrence.[15]

A randomized, double-blind, placebo-controlled study compared the efficacy of different antifungal shampoos, including ciclopirox 1% shampoo, as supplements to oral griseofulvin in children aged 1-12 years with tinea capitis. The shampoos were used twice weekly, first alongside griseofulvin for 8 weeks, and then continued for an additional 24 weeks to assess prevention of recurrence.[15]

This approach addresses both the acute treatment of tinea capitis and the important issue of preventing recurrence, which is common in this condition.

Seborrhea and Seborrheic Dermatitis

Ciclopirox olamine is also effective in treating seborrhea (excessive oiliness of the skin) and seborrheic dermatitis (a common inflammatory skin condition causing flaky, white to yellowish scales to form on oily areas).[13]

A clinical trial compared low-dose oral isotretinoin with topical treatments containing salicylic acid and ciclopirox olamine for seborrhea and seborrheic dermatitis. The topical treatment was applied as a shampoo for scalp and face cleansing every other day for six months.[13]

These conditions affect significant portions of the population (seborrhea affects approximately 30% of people, while seborrheic dermatitis affects 3-5% worldwide) and can negatively impact quality of life. The antifungal properties of ciclopirox are particularly relevant as yeasts of the Malassezia genus play a role in the development of these conditions.[13]

Emerging Uses for Ciclopirox

Hematologic Malignancies

One of the most promising new applications for ciclopirox is in the treatment of blood cancers. A Phase 1 clinical trial has investigated oral ciclopirox olamine for treating relapsed or refractory hematologic malignancies, including various types of leukemia and lymphoma.[1]

This study represented a significant shift from ciclopirox’s traditional use as a topical antifungal to an oral medication targeting cancer. The trial:

  • Administered ciclopirox olamine as an oral suspension
  • Started with a dose of 5 mg/m²/day for 5 days per cycle
  • Included dose escalation to determine the maximum tolerated dose
  • Allowed up to 6 total treatment cycles for patients showing response

The mechanism behind ciclopirox’s potential anticancer effects appears to be related to its effects on survivin expression, a protein involved in cancer cell survival and proliferation. This represents a completely different mechanism than its antifungal actions.[1]

More recently, another Phase I clinical trial (with ATL-001, a ciclopirox olamine oral solution) is investigating the safety, tolerability, and pharmacokinetics of the drug in healthy volunteers at different dose levels (0.2 mg/kg to 4 mg/kg). This step is important for developing ciclopirox as a potential treatment for various conditions beyond its current uses.[6]

Vulvar Cancer Prevention

Another innovative application being studied is the use of ciclopirox lotion for chemoprevention of cancer in the lower female genital tract. A clinical trial has investigated whether regular application of ciclopirox lotion to the vulva could make precancerous lesions shrink or disappear.[3]

This research explores ciclopirox’s potential antineoplastic (anti-cancer) activity, suggesting it may have properties that inhibit the development or growth of tumors. This represents a significant expansion beyond its traditional role as an antifungal agent.[3]

Congenital Erythropoietic Porphyria (CEP)

One of the newest applications being investigated is the use of ciclopirox oral solution (ATL-001) for treating Congenital Erythropoietic Porphyria (CEP), a rare genetic disorder affecting heme production. CEP causes severe photosensitivity, with patients developing painful skin lesions when exposed to sunlight.[10]

A Phase I-II, N-of-1, open-label, prospective study is evaluating whether daily administration of oral ciclopirox can:

  • Reduce the number and severity of sunlight-induced skin lesions
  • Decrease recovery time for lesions
  • Improve other symptoms and clinical signs associated with the disease

This research represents another potential therapeutic application for ciclopirox that extends far beyond its traditional antifungal use.[10]

Safety Information

Ciclopirox has demonstrated a good safety profile across most of its applications, particularly for topical use. After dermal application, only about 1.5% of the applied dose is absorbed through the skin, which helps minimize systemic side effects.[2]

Common side effects of topical ciclopirox may include:

  • Mild skin irritation at the application site
  • Burning or stinging sensation
  • Redness
  • Itching

These side effects are typically mild to moderate in intensity and often resolve without intervention. Clinical studies have consistently shown a low rate of adverse events with topical ciclopirox formulations.[2]

For the newer oral formulations being investigated for conditions like hematologic malignancies or congenital erythropoietic porphyria, safety profiles are still being established through clinical trials. These studies include careful monitoring of adverse events, vital signs, electrocardiogram (ECG) data, physical examinations, and laboratory safety data.[6]

Comparative Studies

Several studies have compared ciclopirox with other antifungal medications to determine relative efficacy, safety, and patient preferences:

  • Ciclopirox vs. Amorolfine for onychomycosis: A study compared patients’ adherence and satisfaction when using ciclopirox nail lacquer versus amorolfine nail lacquer for treating toenail fungus. Ciclopirox required daily application while amorolfine was applied once weekly, which could affect patient compliance.[9]
  • Sequential therapy: A multicenter, randomized, controlled study evaluated a sequential therapy combining RV4104A ointment, ciclopiroxolamine cream, and ciclopirox film-forming solution compared with amorolfine nail lacquer alone for treating dermatophytic onychomycosis without matrix involvement.[12]
  • Comparison with newer agents: A study compared the efficacy of topical MOB015B with ciclopirox 80 mg/g in patients with mild to moderate distal subungual onychomycosis.[14]

These comparative studies help healthcare providers make evidence-based decisions about which antifungal medication might be most appropriate for specific patients and conditions.

Clinical Application Formulation Key Findings
Onychomycosis (Nail Fungus) Nail lacquer, film-forming solution Multiple trials comparing ciclopirox to other treatments like amorolfine. Evaluated for efficacy, safety, and patient adherence. Often used as part of sequential therapy.
Tinea Pedis (Athlete’s Foot) Cream, topical suspension Studies show comparable safety and efficacy between generic ciclopirox formulations and reference products, with superiority over placebo.
Dermatomycoses (Skin Fungal Infections) Cream Found effective and safe in children 3 months to 10 years old with twice daily application for 28 days.
Hematologic Malignancies (Blood Cancers) Oral solution/suspension Phase 1 trials evaluated dose-limiting toxicity, maximum tolerated dose, and effects on survivin expression. Testing different dose levels for safety and efficacy.
Vulvar Cancer Lotion Investigating if regular application can reduce or eliminate precancerous lesions.
Congenital Erythropoietic Porphyria (CEP) Oral solution Exploring potential to improve photosensitivity-related skin lesions and other clinical symptoms in this rare genetic disorder.
Seborrheic Dermatitis Shampoo Used as a comparative treatment alongside other therapies like isotretinoin for reducing sebum secretion and symptoms.
Tinea Capitis (Scalp Ringworm) Shampoo Evaluated as adjunctive treatment to oral griseofulvin, compared with selenium sulfide and ketoconazole shampoos.

FAQ

  • What conditions is ciclopirox being studied to treat in clinical trials? Ciclopirox is being studied for a range of conditions. While it's most commonly tested for fungal infections like onychomycosis (nail fungus), tinea pedis (athlete's foot), and dermatomycoses (skin fungal infections), newer research is exploring its potential in treating blood disorders like leukemia, vulvar cancer, and even a rare genetic condition called Congenital Erythropoietic Porphyria (CEP). This versatility shows ciclopirox may have broader applications beyond its traditional antifungal uses.
  • How is ciclopirox administered in clinical trials? In clinical trials, ciclopirox is administered in several different forms depending on the condition being treated. For nail infections (onychomycosis), it's commonly used as a nail lacquer or solution applied directly to the affected nails. For skin conditions, it's available as a cream, gel, or topical suspension. For more serious conditions like blood disorders, researchers are testing oral formulations where ciclopirox is taken by mouth in specific doses, usually for 5 days in a treatment cycle.
  • What makes ciclopirox effective against fungal infections? Ciclopirox works through multiple mechanisms that make it effective against fungi. It inhibits the cellular uptake of essential substances needed for fungal metabolism and growth. It also binds irreversibly to cell structures such as mitochondria, ribosomes, microsomes, and the cell wall of fungi. This broad spectrum of activity allows ciclopirox to work against dermatophytes (fungi that cause skin infections), yeasts, molds, actinomycetes, and even some bacteria, making it versatile for various fungal infections.
  • Are there any new or unexpected uses for ciclopirox being studied? Yes, researchers are exploring several surprising new uses for ciclopirox. Most notably, it's being studied as a potential cancer treatment, including for blood cancers like leukemia and vulvar cancer. One study is examining ciclopirox's effects on survivin expression (a protein involved in cancer cell survival) in patients with blood cancers. Another innovative use being researched is for Congenital Erythropoietic Porphyria (CEP), a rare genetic disorder that causes extreme skin sensitivity to light, where ciclopirox may help improve skin lesions and other symptoms.
  • How does ciclopirox compare to other antifungal treatments in clinical trials? Several clinical trials directly compare ciclopirox to other antifungal treatments. For example, studies have compared ciclopirox nail lacquer to amorolfine nail lacquer for treating nail fungus, evaluating factors like efficacy, safety, patient adherence, and satisfaction. In another study, researchers compared a ciclopirox cream formulation to a reference product for treating tinea pedis (athlete's foot). These comparative studies help determine which treatments work best for specific conditions and patient populations, with ciclopirox generally showing comparable efficacy to other antifungals while having its own unique properties.

Ongoing Clinical Trials on CICLOPIROX

  • Study on the Effect of Ciclopirox in Treating Nail Fungal Infection in Patients

    Recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Spain

Glossary

  • Onychomycosis: A fungal infection of the fingernails or toenails that causes thickening, discoloration, and separation from the nail bed. It's the most common nail disorder, often requiring long-term treatment.
  • Tinea Pedis: Also known as athlete's foot, this is a fungal infection that usually begins between the toes and can cause itching, burning, and stinging sensations along with red, scaly skin.
  • Dermatomycoses: A general term for fungal infections of the skin, hair, and nails, caused by various fungi including dermatophytes, yeasts, and molds.
  • Ciclopirox Olamine: The salt form of ciclopirox that is commonly used in medicinal preparations. It has the same antifungal properties as ciclopirox.
  • Hematologic Malignancy: Cancers that affect the blood, bone marrow, and lymph nodes. These include various types of leukemia, lymphoma, and myeloma.
  • Maximum Tolerated Dose (MTD): The highest dose of a drug that does not cause unacceptable side effects. This is often determined during Phase I clinical trials.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including how it's absorbed, distributed, metabolized, and excreted.
  • Mycological Cure: The elimination of a fungal infection as confirmed by laboratory tests, typically involving negative results on both microscopic examination and fungal culture.
  • Clinical Cure: The resolution of visible signs and symptoms of an infection or disease, as determined by a healthcare provider's examination.
  • Therapeutic Success: In fungal infection studies, this typically means achieving both mycological cure (negative laboratory tests) and clinical cure (visible improvement or resolution of symptoms).
  • KOH (Potassium Hydroxide) Test: A laboratory method used to detect fungal elements in skin, hair, or nail samples by dissolving keratin and making fungal structures more visible under a microscope.
  • Congenital Erythropoietic Porphyria (CEP): A rare genetic disorder affecting the production of heme (a component of hemoglobin), leading to severe skin photosensitivity, anemia, and other complications.
  • Distal Lateral Subungual Onychomycosis (DLSO): The most common form of nail fungus that begins at the tip or sides of the nail and slowly spreads toward the cuticle.
  • Tinea Capitis: A fungal infection of the scalp, also known as ringworm of the scalp, which can cause scaling, inflammation, and hair loss.
  • Dermatophyte: A type of fungus that infects the skin, hair, and nails by digesting keratin, the structural protein found in these tissues.

References

  1. https://clinicaltrials.gov/study/NCT00990587
  2. https://clinicaltrials.gov/study/NCT01646580
  3. https://clinicaltrials.gov/study/NCT00382330
  4. https://clinicaltrials.gov/study/NCT01419847
  5. https://clinicaltrials.gov/study/NCT00804193
  6. https://clinicaltrials.gov/study/NCT05647343
  7. https://clinicaltrials.gov/study/NCT00802672
  8. https://clinicaltrials.gov/study/NCT02644551
  9. https://clinicaltrials.gov/study/NCT02679911
  10. https://clinicaltrials.gov/study/NCT07024316
  11. https://clinicaltrials.gov/study/NCT05809297
  12. https://clinicaltrials.gov/study/NCT01014637
  13. https://clinicaltrials.gov/study/NCT01139749
  14. https://clinicaltrials.gov/study/NCT02866032
  15. https://clinicaltrials.gov/study/NCT00127868