An Efficacy Study of a New Formulation of Ketoconazole 2% Cream in Patients With Tinea Pedis, Commonly Known as Athlete's Foot

An Efficacy Study of a New Formulation of Ketoconazole 2% Cream in Patients With Tinea Pedis, Commonly Known as Athlete's Foot

A Double-Blind, Randomized, Parallel Group Comparison of Nizoral Cream (F012), Ketoconazole 2% Cream (F126) and Placebo (F000) in the Treatment of Interdigital Tinea Pedis

Unexpected discordant results between the KOH microscopy and mycological culture tests at three study sites in the UK.

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.

This is a randomized (study drug assigned by chance), double-blind (neither the physician nor the patient knows the name of the assigned treatment), multicentre study in Poland and the United Kingdom designed to assess the mycological (fungal) cure rate and clinical efficacy of a new formulation of ketoconazole 2% cream (F126) with the current formulation of ketoconazole 2% cream (Nizoral) (F012) compared with placebo cream in patients with symptomatic uncomplicated interdigital (between the toes) Tinea pedis, a skin infection commonly known as "athlete's foot" that is caused by a kind of mold called a fungus. Approximately 548 patients who have symptomatic uncomplicated interdigital Tinea pedis confirmed by positive potassium hydroxide (KOH) microscopy (examination using a microscope) and mycological (fungal) culture will be randomized to receive 1 of 2 formulations of ketoconazole 2% cream (formulation F012 or F126) or placebo cream. There will be 4 study visits during the study. At Visit 1 (baseline), patients will sign the informed consent and be assessed for mycological and clinical signs and symptoms of Tinea pedis. Baseline demographics (age, race, etc), medical history and medication (s) that the patient is currently taking will be recorded. Patients will be issued with a tube of the cream and instructed to apply the cream sparingly to all affected areas of the foot (or feet), once daily (at night or in the evenings) for a total of 4 weeks according to protocol-specified guidelines. During the 4-week treatment period patients will return to the study every 2 weeks to be assessed for clinical signs and symptoms. After the 4-week treatment period, patients will continue participation in the study for an additional 2 weeks without medication. Patients will return then return to the study center for a final visit (Visit 4, Week 6) at which time skin scrapings will be sampled from interdigital spaces on both feet for KOH microscopy and mycological culture. The primary efficacy endpoint is to determine whether a new formulation of ketoconazole 2% cream is equivalent (or as effective) as the current formulation of ketoconazole 2% cream (Nizoral) compared to a placebo cream in achieving a mycological cure (defined as negative KOH microscopy and negative mycological culture) following 4 weeks of treatment. The primary outcome measure in the study is a mycological cure (defined as negative KOH microscopy and negative mycological culture) at week 6. Patients will be monitored for safety (occurrence of adverse events, use of concomitant medications, and reasons for premature discontinuation from the study) from Visit 1 through Visit 4 (Week 6 or time of early termination from study). Patients will be provided with up to two 15g tubes of ketoconazole cream (formulation F126 or F012) or matching placebo cream and be instructed to apply cream sparingly to affected areas of the feet once daily at night or in the evening for 4 weeks according to protocol specified guidelines.

ketoconazole 2% cream (formulation F126) A topical white homogenous cream containing the equivalent of 20 mg (or 2%) of ketoconazole applied sparingly to all affected areas of the foot (or feet) once daily (at night or in the evenings) for a total of 4 weeks.

ketoconazole 2% cream (formulation F012) (Nizoral) A topical white homogenous cream containing the equivalent of 20 mg (or 2%) of ketoconazole identical in appearance to study drug applied sparingly to all affected areas of the foot (or feet) once daily (at night or in the evenings) for a total of 4 weeks.

Placebo cream A topical white homogenous cream identical in appearance to study drug applied sparingly to all affected areas of the foot (or feet) once daily (at night or in the evenings) for a total of 4 weeks.

A topical, white, homogenous cream identical in appearance to study drug applied sparingly to all affected areas of the foot (or feet), once daily (at night or in the evenings) for a total of 4 weeks.

A topical, white, homogenous cream containing the equivalent of 20 mg (or 2%) of ketoconazole identical in appearance to study drug applied sparingly to all affected areas of the foot (or feet), once daily (at night or in the evenings) for a total of 4 weeks.

A topical, white, homogenous cream containing the equivalent of 20 mg (or 2%) of ketoconazole applied sparingly to all affected areas of the foot (or feet), once daily (at night or in the evenings) for a total of 4 weeks.

The Number of Patients in the Positive Baseline Culture Set (PBCS) With Mycological Cure (MC) at Week 6

Mycological Cure (MC) was defined as having a negative potassium hydroxide (KOH) microscopy and negative fungal culture at Week 6.

Overall Cure (OC) was defined as Mycological Cure (MC) in addition to a global clinical evaluation of either 'Completely Cleared' (clearance of all signs and symptoms of Tinea pedis) or 'Marked Improvement' (significant improvement of signs and symptoms of Tinea pedis; residual signs and symptoms only), assessed at Week 6.

Inclusion Criteria: Be co-operative, reliable and sufficiently competent to grade and record symptoms as requested have a clinical diagnosis of uncomplicated interdigital Tinea pedis confirmed by KOH microscopy Be either post-menopausal or surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before entry and throughout the study and have a negative urine pregnancy test at screening (applies to women only) Sign an informed consent form indicating an understanding of the purpose of and procedures required for the study and willingness to participate in the study Exclusion Criteria: Have complicated Tinea pedis defined as confluent, diffuse moccasin type tinea pedis of the entire plantar surface (undersurface of foot), onychomycosis (fungal nail infection) other dermatomycosis (fungal skin infection) requiring active treatment Have a previous sensitivity to imidazole antifungal agents or to any ingredient of the study medication Have a history of disallowed therapies including oral (by mouth) antifungal treatments within the previous 6 weeks, recent use (within 2 weeks of the study start) of topical antifungal agent, immunosuppressive or radiation therapy within the previous 4 weeks, recent use (within 2 weeks prior to screening) of other oral antibiotics, systemic corticosteroids or topical corticosteroids or antibiotics applied to the feet Be HIV-positive (testing will not be performed) Have uncontrolled diabetes mellitus or peripheral vascular disease requiring active treatment