Otomycosis
Conditions
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.
Interventions
DRUG7-Day Miconazole Oil (Miconazole 2%)
7 days of 2x per day treatment with Miconazole Oil (Active Drug Product 2% Miconazole)
DRUG14-Day Miconazole Oil (Miconazole 2%)
14 days of 2x per day treatment with Miconazole Oil (Active Drug Product 2% Miconazole)
DRUG14-Day Placebo - Oil Vehicle
14 days of 2x per day treatment with Placebo - Oil Vehicle, Study Drug base without active ingredient
Sponsors
QST Consultations, Ltd.
Hill Dermaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Subjects, investigators, and study staff will not be masked as to the treatment duration assigned to each subject (7 versus 14 days). For subjects receiving the 14-day treatment with study drug, the contents of the study drug (active versus placebo) will be masked to the subject, investigator, and study staff.
Eligibility
Sex/Gender
ALL
Age
25 Months to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 7-Day Miconazole Oil (Miconazole 2%) 7 days of 2x per day of treatment with Miconazole Oil (Active Drug Product 2% Miconazole)
7-Day Miconazole Oil (Miconazole 2%): 7 days of 2x per day treatment with Miconazole Oil (Active Drug Product 2% Miconazole) | 23 |
| 14-Day Miconazole Oil (Miconazole 2%) 14 days of 2x per day of treatment with Miconazole Oil (Active Drug Product 2% Miconazole)
14-Day Miconazole Oil (Miconazole 2%): 14 days of 2x per day treatment with Miconazole Oil (Active Drug Product 2% Miconazole) | 22 |
| 14-Day Placebo - Oil Vehicle 14 days of 2x per day of treatment with Placebo - Oil Vehicle, Study Drug base without active ingredient
14-Day Placebo - Oil Vehicle: 14 days of 2x per day treatment with Placebo - Oil Vehicle, Study Drug base without active ingredient | 20 |
| Total | 65 |
Baseline characteristics
| Characteristic | 14-Day Miconazole Oil (Miconazole 2%) | 7-Day Miconazole Oil (Miconazole 2%) | Total | 14-Day Placebo - Oil Vehicle |
|---|---|---|---|---|
| Age, Continuous | 66.0 years | 64.0 years | 64 years | 62.5 years |
| Debris None | 10 Participants | 11 Participants | 27 Participants | 6 Participants |
| Debris Scant, moderate or Heavy | 12 Participants | 12 Participants | 38 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 22 Participants | 60 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Mycological culture Negative mycological culture | 10 Participants | 11 Participants | 27 Participants | 6 Participants |
| Mycological culture Positive mycological culture | 12 Participants | 12 Participants | 38 Participants | 14 Participants |
| Pain Absent | 12 Participants | 14 Participants | 35 Participants | 9 Participants |
| Pain Present | 10 Participants | 9 Participants | 30 Participants | 11 Participants |
| Presence of fungal elements Absent | 10 Participants | 11 Participants | 27 Participants | 6 Participants |
| Presence of fungal elements Present | 12 Participants | 12 Participants | 38 Participants | 14 Participants |
| Pruritus - investigator assessed Mild, moderate or severe | 11 Participants | 10 Participants | 35 Participants | 14 Participants |
| Pruritus - investigator assessed None | 11 Participants | 13 Participants | 30 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 21 Participants | 55 Participants | 16 Participants |
| Region of Enrollment United States | 22 Participants | 23 Participants | 65 Participants | 20 Participants |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 32 Participants | 11 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 33 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 22 | 0 / 20 |
| other Total, other adverse events | 9 / 23 | 10 / 22 | 15 / 20 |
| serious Total, serious adverse events | 0 / 23 | 0 / 22 | 0 / 20 |
Outcome results
Primary
Primary Efficacy Endpoint
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.
Time frame: At Test of Cure visit (Day 15 for 7 Day Active and Day 22 for 14 Day Active and 14 Day Vehicle)
Population: Actual number of participants analyzed under Primary efficacy endpoint are MITT population, defined as subjects who had a clinical diagnosis of otomycosis confirmed by positive fungal culture.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 7-Day Miconazole Oil (Miconazole 2%) | Primary Efficacy Endpoint | 1 Participants |
| 14-Day Miconazole Oil (Miconazole 2%) | Primary Efficacy Endpoint | 3 Participants |
| 14-Day Placebo - Oil Vehicle | Primary Efficacy Endpoint | 1 Participants |
Secondary
Secondary Efficacy Endpoints
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).
Time frame: At Test of Cure visit (Day 15 for 7 Day Active and Day 22 for 14 Day Active and 14 Day Vehicle)
Population: Percentage of subjects in the MITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 7-Day Miconazole Oil (Miconazole 2%) | Secondary Efficacy Endpoints | Clinical Cure | 2 Participants |
| 7-Day Miconazole Oil (Miconazole 2%) | Secondary Efficacy Endpoints | Negative Fungal Culture | 4 Participants |
| 7-Day Miconazole Oil (Miconazole 2%) | Secondary Efficacy Endpoints | Secondary Therapeutic Cure | 3 Participants |
| 7-Day Miconazole Oil (Miconazole 2%) | Secondary Efficacy Endpoints | Secondary Clinical Cure | 7 Participants |
| 14-Day Miconazole Oil (Miconazole 2%) | Secondary Efficacy Endpoints | Secondary Clinical Cure | 6 Participants |
| 14-Day Miconazole Oil (Miconazole 2%) | Secondary Efficacy Endpoints | Clinical Cure | 4 Participants |
| 14-Day Miconazole Oil (Miconazole 2%) | Secondary Efficacy Endpoints | Secondary Therapeutic Cure | 5 Participants |
| 14-Day Miconazole Oil (Miconazole 2%) | Secondary Efficacy Endpoints | Negative Fungal Culture | 5 Participants |
| 14-Day Placebo - Oil Vehicle | Secondary Efficacy Endpoints | Secondary Clinical Cure | 4 Participants |
| 14-Day Placebo - Oil Vehicle | Secondary Efficacy Endpoints | Negative Fungal Culture | 3 Participants |
| 14-Day Placebo - Oil Vehicle | Secondary Efficacy Endpoints | Secondary Therapeutic Cure | 1 Participants |
| 14-Day Placebo - Oil Vehicle | Secondary Efficacy Endpoints | Clinical Cure | 2 Participants |