Phase III Efficacy and Safety Study of Miconazole Oil for Otomycosis

Inclusion Criteria:

1. Male or non-pregnant, non-lactating females

2. Diagnosis of uncomplicated otomycosis of the external ear only, in the ear(s) thatwill be treated with study drug, with a score for fungal elements of 1 in each earto be treated with study drug (see Section 7.4 for definitions of the scores foreach of the otomycosis signs and symptoms). Subjects must also have the followingsigns and symptoms of otomycosis in the study ear: pruritus ≥2; debris ≥2; and auralfullness ≥2.

3. General good health as determined by medical examination and medical history, andwho are free of clinically significant disease, including diabetes mellitus that isnot well-controlled or that could interfere with the study

4. Females of childbearing potential must have had a negative urine pregnancy test atScreening/Baseline and must agree to use an effective method of contraception (asdefined in Section 8.5) from Screening/Baseline up through the End of Treatmentvisit (see Section 6). Females of childbearing potential include any female who hasexperienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is notpostmenopausal (defined as amenorrhea >12 consecutive months). Females who are usingoral, implanted, or injectable contraceptive hormones, an intrauterine device (IUD),barrier methods (diaphragm, condoms, spermicide) to prevent pregnancy, practicingabstinence or where partner is sterile (e.g., vasectomy), should be considered to beof childbearing potential

5. Subjects and/or their caregivers (as appropriate for the age of the subject) musthave full legal capacity to volunteer

6. Subjects and/or their caregivers must have completed an appropriately administeredinstitutional review board (IRB)-approved informed consent and assent (asapplicable) prior to any study related procedures

7. Subjects and their caregivers (as applicable) must agree to comply with allrequirements of the protocol

8. For subjects with only one ear meeting all study eligibility criteria, the subjectwill be eligible for the study, and the ear meeting all eligibility criteria will betreated with study drug and considered to be the study ear for the purposes of studyevaluations. In case of bilateral otomycosis in which at least one ear meet allstudy eligibility criteria, the subject will be eligible for the study, both earsmay be treated with study drug provided that both ears have a score of 1 for fungalelements, and the worse ear will be considered to be the study ear for the purposesof study evaluations. If both ears meet study eligibility criteria and aredetermined by the investigator to have the same degree of infection atScreening/Baseline, the left ear will be considered to be the study ear for thepurposes of study evaluations.

Exclusion Criteria:

1. Any other dermatoses or conditions of the ear that may interfere with the evaluationof otomycosis, including concomitant otic infections (including bacterial infection)that require antimicrobial treatment, disease that has spread beyond the externalear(s), or pre-existing skin atrophy of the affected ear(s) that will be treatedwith study drug

2. Tympanostomy tube or perforated tympanic membrane in the ear(s) that will be treatedwith study drug

3. History of prior surgery directly affecting and compromising the external auditorycanal and/or tympanic membrane of the ear(s) that will be treated with study drug,except for prior tympanostomy tube(s) that have already been removed and completelyhealed

4. Use of any topical medicated treatments for otomycosis within 14 days of study entryfor the ear(s) that will be treated with study drug

5. Use of any systemic antifungal therapy within 28 days of study entry, warfarinwithin 28 days of study entry, immunosuppressive or immune-stimulating drugs within 28 days of study entry, or systemic steroids within 3 months of study entry

6. Fever of ≥100°F at study entry

7. Recurrent otomycosis that has been unresponsive to previous antifungal treatmentwithin the last 12 months

8. Known hypersensitivity to any of the components in the test formulation

9. Participation in another investigative trial within 28 days of study entry.