Dose-Ranging Study for Miconazole Oil for Treatment of Otomycosis
Dose-Ranging Study for Miconazole Oil for Treatment of Otomycosis
The purpose of the study is to evaluate the efficacy and safety of active treatment
 (miconazole oil) for 7 versus 14 days, and to compare 14 days of active treatment (miconazole
 oil) to inactive treatment (placebo) over a 14-day treatment duration, in subjects with
 fungal infection (otomycosis) of the external ear.
Miconazole, an imidazole antifungal agent, is commonly used for different types of fungal
 skin infections, such as Candida, ringworm, jock itch, athlete's foot, nail fungus, vaginal
 yeast infections, and oropharyngeal candidiasis. The 2% formulation of miconazole is commonly
 used for dermatophytic infections. The mechanisms of action of miconazole against fungi in
 general appear to be applicable to fungi associated with otomycosis, in that miconazole has
 been demonstrated to have activity in vitro against some clinical isolates of fungi
 associated with human otomycosis in the US.

 Miconazole targets the cytochrome P450-dependent enzyme 14-α-sterol demethylase, an enzyme
 that is also involved in mammalian cholesterol synthesis, resulting in inhibition of
 ergosterol biosynthesis in the cell membrane of the fungal organism. Because ergosterol is an
 important component of the cell membrane, inhibition of its synthesis inhibits fungal cell
 growth.

 In addition to its activity toward the enzyme 14-α-sterol demethylase, miconazole also leads
 to increased reactive oxygen species in fungal organisms, which appears to result in
 fungicidal activity.
Inclusion Criteria:

 -  Uncomplicated otomycosis of the external ear only, age more than 2 year

 Exclusion Criteria:

 -  Pregnancy

 -  Other dermatoses or conditions of the ear that may interfere with the evaluation of
 otomycosis, including concomitant otic infections (including bacterial infection) that
 require antimicrobial treatment, disease that has spread beyond the external ear(s),
 or pre-existing skin atrophy of the affected ear(s)

 -  Tympanostomy tube or perforated tympanic membrane in the ear(s) that will be treated

 -  Previous surgery affecting the ear(s) that will be treated, except for prior
 tympanostomy tube(s) that had been removed and had completely healed

 -  Previous use of medicated treatments for otomycosis or participation in another
 investigational study within 28 days of study entry

 -  Previous use of any systemic antifungal therapy, warfarin, and immunosuppressive or
 immune-stimulating drugs within 28 days of study entry, or systemic steroids within 3
 months of study entry

 -  Recurrent otomycosis that had been unresponsive to previous antifungal treatment

 -  Known hypersensitivity to any of the components in the test formulation