Dose-Ranging Study for Miconazole Oil for Treatment of Otomycosis

Phase 2

Completed

• Conditions: Otomycosis
• Interventions: Drug: 7-Day Miconazole Oil (Miconazole 2%); Drug: 14-Day Miconazole Oil (Miconazole 2%); Drug: 14-Day Placebo - Oil Vehicle

• Registration Number: NCT03130738
• Lead Sponsor: Hill Dermaceuticals, Inc.

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2017-04-20
• Study First Submitted: 2017-04-21
• Study First Submitted QC: 2017-04-25
• Study First Posted: 2017-04-26
• Primary Completion: 2019-08-06
• Study Completion: 2019-08-06
• Results First Submitted: 2020-04-08
• Results First Submitted QC: 2020-04-23
• Results First Posted: 2020-05-08
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-06
• Last Update Posted: 2022-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
7-Day Miconazole Oil (Miconazole 2%)	7-Day Miconazole Oil (Miconazole 2%)	7 days of 2x per day of treatment with Miconazole Oil (Active Drug Product 2% Miconazole)
14-Day Miconazole Oil (Miconazole 2%)	14-Day Miconazole Oil (Miconazole 2%)	14 days of 2x per day of treatment with Miconazole Oil (Active Drug Product 2% Miconazole)
14-Day Placebo - Oil Vehicle	14-Day Placebo - Oil Vehicle	14 days of 2x per day of treatment with Placebo - Oil Vehicle, Study Drug base without active ingredient

Primary Outcome Measures

Name	Time	Method
Primary Efficacy Endpoint	At Test of Cure visit (Day 15 for 7 Day Active and Day 22 for 14 Day Active and 14 Day Vehicle)	Percentage of subjects in MITT population, at the "Test of Cure" visit with "Therapeutic cure", defined as a negative fungal culture plus "clinical cure" defined as the absence of all otomycosis signs and symptoms for pruritus, debris, fungal elements, and pain.

Secondary Outcome Measures

Name	Time	Method
Secondary Efficacy Endpoints	At Test of Cure visit (Day 15 for 7 Day Active and Day 22 for 14 Day Active and 14 Day Vehicle)	1. Percentage of subjects in MITT population with clinical cure at the Test of Cure Visit; 2. Percentage of subjects in MITT population with a negative fungal culture at the Test of Cure Visit; 3. Percentage of subjects in MITT population with a negative fungal culture at the Test of Cure visit as well as individual sign or symptom score of 0 or 1 on each of the scales for pruritus and debris and a score of 0 on each of the scales for fungal elements and pain (Secondary therapeutic cure).; 4. Percentage of subjects in MITT population with individual signs or symptoms with a score of 0 or 1 on each of the scales for pruritus and debris and a score of 0 on each of the scales for fungal elements and pain (Secondary clinical cure).

Trial Locations

Locations (6)

University of California San Diego; 🇺🇸 La Jolla, California, United States

Ear Nose and Throat Associates of Southe Florida; 🇺🇸 Boynton Beach, Florida, United States

Silverstein Institute; 🇺🇸 Sarasota, Florida, United States

Head and Neck Surgery Specialist; 🇺🇸 Chula Vista, California, United States

Piedmont ENT Associates; 🇺🇸 Winston-Salem, North Carolina, United States

Advanced ENT and Allergy; 🇺🇸 Louisville, Kentucky, United States