Efficacy and Safety Study of Miconazole Oil Versus Vehicle on Fungal Infection of the Ear Canal (Otomycosis)

NCT04432376 | Completed Phase 2 Results FDA Drug

• 1 other identifier: MZ-0120-ESP3-052
• Study Type: interventional
• Target: 382
• Locations: 1 country
• Sites: 12

Brief Summary

This study involves two portions, a randomized, double-blind portion and an open-label portion, to evaluate the efficacy and safety of Miconazole oil 2% versus its Vehicle in the treatment of fungal infection of the outer ear canal (Otomycosis). The subjects randomized in the first portion of the study will have active fungal infection of the ear(s) and will be treated with either Miconazole Oil or the Vehicle for 14 days twice daily, 5 drops into the affected ear(s) per dose. The subjects enrolled in the open-label portion of the study may or may not have active fungal infection of the ear(s), and will be given the Miconazole Oil active drug following the same application of 5 drops into the ear(s) twice daily for 14 days. The intention of the study is to evaluate the efficacy of Miconazole Oil on fungal infection of the ears when applied using 5 drops into the ear(s) twice daily for 14 days continuously. This study also intends to show safety of Miconazole Oil 5 drops into each ear twice a day for 14 consecutive days.

Conditions

Otomycosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects With Therapeutic Cure

  "therapeutic cure" is "mycological cure" plus "clinical cure, in the Modified intent to treat (MITT) only: patients with + fungal culture at baseline. Fungal culture results verified as (+) or (-) after enrollment. Intent to treat (ITT) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%). Mycological cure is a negative mycological culture (culture is either positive or negative). Score=0 is best. Clinical cure is absence of all otomycosis signs and symptoms (s/s) of Pruritus, Debris, and Aural fullness, graded as (scores) 0=none, 1=mild, 2=moderate, 3=severe; and Presence of fungal elements, score 0=No fungal elements, 1=fungal elements present on visual inspection. Score=0 is best. Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline.

  21 days from first day of drug application

Secondary Outcomes (2)

• Percentage of Subjects With Mycological Cure

  21 days from first day of drug application

• Percentage of Subjects With Clinical Cure

  21 days from first day of drug application

Study Arms (3)

Active treatment arm

ACTIVE COMPARATOR

Treatment with miconazole 2% oil, 5 drops into each ear twice daily for 14 consecutive days

Drug: miconazole 2% oil

Placebo treatment arm

PLACEBO COMPARATOR

Treatment with the vehicle oil, placebo, 5 drops into each ear twice daily for 14 consecutive days

Drug: vehicle oil

Open-label treatment arm

OTHER

Application of miconazole 2% oil, 5 drops into each ear twice daily for 14 consecutive days

Drug: miconazole 2% oil

Interventions

miconazole 2% oil DRUG

Drug treatment of otomycosis for 14 days

Also known as: active treatment

Active treatment arm; Open-label treatment arm

vehicle oil DRUG

Placebo treatment of otomycosis for 14 days

Also known as: placebo treatment

Placebo treatment arm

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Randomized blinded initial phase of study:
• Male or non-pregnant, non-lactating females with a clinical diagnosis of uncomplicated otomycosis of the external ear only,
• Intact tympanic membrane in the ear(s) to be treated with study drug,
• In general good health as determined by medical examination and medical history,
• Free of clinically significant disease, including diabetes mellitus, that is not well-controlled or that could interfere with the study.
• Open-label second phase of study:
• Male or non-pregnant, non-lactating females with an intact tympanic membrane in the ear(s) to be treated with study drug,
• In general good health as determined by medical examination and medical history,
• Free of clinically significant disease, including diabetes mellitus, that is not well-controlled or that could interfere with the study.

You may not qualify if:

• Presence of dermatoses or conditions of the ear that may interfere with evaluation of otomycosis or with safety evaluations, including concomitant otic infections 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;
• History of prior surgery directly affecting and compromising the external auditory canal and/or tympanic membrane, except for prior tympanostomy tube(s) that have already been removed and completely healed;
• Use of any topical medicated treatments for otomycosis within 14 days of study entry;
• Use of any systemic antifungal therapy within 28 days of study entry, warfarin within 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;
• Fever of ≥100°F at study entry;
• Otomycosis that has been unresponsive to previous antifungal treatment;
• Known hypersensitivity to any of the components in the test formulation;
• Participation in another investigative trial within 28 days of study entry

Sponsors & Collaborators

• Hill Dermaceuticals, Inc.: lead
• Abond CRO Inc.: collaborator

Study Sites (12)

Head and Neck Surgery Specialists

Chula Vista, California, 91910, United States

Location

UCSD

La Jolla, California, 92037, United States

Location

DaVinci Research, LLC

Roseville, California, 95661, United States

Location

Sacramento ENT / DaVinci Research

Sacramento, California, 95815, United States

Location

Lake ENT & FPS

Leesburg, Florida, 34748, United States

Location

Advanced ENT & Allergy

Louisville, Kentucky, 40220, United States

Location

DelRicht Research

New Orleans, Louisiana, 70124, United States

Location

University of Missouri

Columbia, Missouri, 65212, United States

Location

OnSite Clinical Solutions

Dillon, South Carolina, 29536, United States

Location

Carolina ENT

Orangeburg, South Carolina, 29118, United States

Location

West Houston Clinical Research Services

Houston, Texas, 77055, United States

Location

Research Your Health

Plano, Texas, 75093, United States

Location

MeSH Terms

Conditions

Otomycosis

Interventions

Miconazole; Oils

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections; Ear Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Lipids

Limitations and Caveats

The limited number of patients with otomycosis at any one time, and the lack of standardized FDA-approved clinical studies on otomycosis have proven to be challenging and difficult to assign predetermined analysis endpoints. This is in line with the challenges described in the FDA Accelerating Rare disease Cures Program, such as challenges faced when using well-established trial designs, and complexities in endpoint selection when there is limited information or understanding of the disease.

Results Point of Contact

• Title: Dr. Rosario G Ramirez, Medical Director
• Organization: Hill Dermaceuticals

nini.ramirez@hillderm.com

4073231887

Study Officials

• Arnaldo Rivera, MD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

• Quyen T Nguyen, MD

  UCSD

  PRINCIPAL INVESTIGATOR

• Kenneth Hodge, MD

  Advanced ENT and Allergy

  PRINCIPAL INVESTIGATOR

• Patrick Dennis, MD

  DelRicht Research

  PRINCIPAL INVESTIGATOR

• Sammy Vaught, MD

  Lake ENT & FPS

  PRINCIPAL INVESTIGATOR

• Timothy Fitzgibbon, MD

  OnSite Clinical Solutions

  PRINCIPAL INVESTIGATOR

• John Ansley, MD

  Carolina ENT

  PRINCIPAL INVESTIGATOR

• Randall Ow, MD

  DaVinci Research LLC

  PRINCIPAL INVESTIGATOR

• Oscar DeValle, MD

  West Houston Clinical Research Service

  PRINCIPAL INVESTIGATOR

• Linda Woo, MD

  Head and Neck Surgery Specialists

  PRINCIPAL INVESTIGATOR

• Brent Benscoter, MD

  Sacramento ENT / DaVinci Research

  PRINCIPAL INVESTIGATOR

• Jeffrey Adelglass, MD

  Research Your Health

  PRINCIPAL INVESTIGATOR

• Gary Brandt, MD

  Delricht

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Clinical Investigators, study staff and subjects randomized to the initial phase of the study are blinded to active drug and placebo.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two phases; initial is randomized double-blind active vs placebo on a pre-determined number of subjects with otomycosis, to finish before starting second phase. Second phase is open-label use on diseased or healthy subjects to evaluate safety. Subjects from initial phase may crossover to second phase open-label if they meet the requirements, and new diseased or healthy subjects meeting requirements may enroll in this open-label phase.

Study Record Dates

• First Submitted: June 11, 2020
• First Posted: June 16, 2020
• Study Start: July 8, 2020
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: January 19, 2024
• Results First Posted: November 4, 2022

Record last verified: 2024-01

Locations

US (12)