Absorption and Systemic Study of AN2690 in Patients With Moderate to Severe Onychomycosis (ADME II)

Study Overview
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Brief Summary
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The purpose of the study is to determine the absorption and systemic pharmacokinetics of AN2690 following daily application to all ten (10) toenails for 28 days.

Detailed Description
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A single center, open-label, multiple-dose study design will be used. Planned enrollment is 20 subjects to complete 15. Subjects must have a clinical diagnosis of onychomycosis of each great toenail and a clinical diagnosis of onychomycosis of six of the remaining toenails.

Official Title
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An Open-label, Multiple-dose Study Of The Absorption And Systemic Pharmacokinetics Of An2690 Applied As A 7.5% Solution To All Toenails Of Adult Patients With Moderate To Severe Onychomycosis

Conditions
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Onychomycosis

Intervention / Treatment
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* Drug: AN2690


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 and ≤65 BMI between 18.5 and 35 inclusive Moderate to severe onychomycosis involving ≥80% of both great toenails, as determined by visual inspection after the nail has been trimmed Combined thickness of the nail plate and nail bed of each great toenail is >3mm At least 6 additional toenails with a clinical diagnosis of onychomycosis If a female of childbearing potential, must be using of a highly effective method of birth control or abstinence and be willing to remain on that same method of birth control throughout the study Capable of understanding and signing the informed consent, and willing to comply with all requirements of the study Exclusion Criteria: History of allergy to any of the study drug or any components in the test product(s) or history of hypersensitivity or allergic reactions to any of the study preparations as described in the Investigator's Brochure Clinically significant laboratory abnormalities that would interfere with the conduct or interpretation of the study or jeopardize his/her safety Diabetes mellitus requiring treatment other than diet and exercise Willing to refrain from the use of nail cosmetics such as clear and or colored nail lacquers from the screening visit until the end of the study Nursing, pregnant or planning to become pregnant during the study Failure to complete the specified washout period(s) for the following topical: Topical antifungal applied to the feet (does not include antifungals for treatment of T. pedis during the study): 4 weeks Anti-inflammatories, corticosteroids, topical immunomodulators: 2 weeks Failure to complete the specified washout period(s) for the following systemic medications: Corticosteroids (including intramuscular injections): 2 weeks Antifungals for treatment of onychomycosis or any systemic antifungal with known activity against dermatophyte: 24 weeks Systemic immunomodulators: 4 weeks Received treatment of any type for cancer within the last 6 months History of any significant internal disease Nail or anatomic abnormalities of the toe, e.g., genetic nail disorders, primentary disorders, onychogryphosis, trauma to the nail(s) to be treated AIDS or AIDS related complex History of street drug or alcohol abuse Donated or lost blood, or participated in a clinical study which involved the withdrawal of a large volume of blood (480 mL or more), during the six-week period preceding study initiation Donated plasma during the two week period preceding study initiation Participated in any other trial of an investigational drug or device within 30 days prior to enrollment or participation in a research study concurrent with this study Prior enrollment in a study using the study drug, AN2690

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: AN2690|AN2690 7.5% Solution, once daily for 28 days|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of AN2690 in plasma and the concentration of AN2690 in urine over time |  | Days 0, 1, 14, 15, and 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy measures of linear toenail growth, fungal culture results, KOH results, and clear toenail growth |  | Days 0, 14, 28, and 42 | 
| Safety and tolerance assessed by application site reactions, adverse events, vital signs, physical examinations, and 12-lead EKG |  | Days 0-28, and 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Onychomycosis, Fungal Nail