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

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

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.

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.

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:

  1. Topical antifungal applied to the feet (does not include antifungals for treatment of T. pedis during the study): 4 weeks
  2. Anti-inflammatories, corticosteroids, topical immunomodulators: 2 weeks

• Failure to complete the specified washout period(s) for the following systemic medications:

  1. Corticosteroids (including intramuscular injections): 2 weeks
  2. Antifungals for treatment of onychomycosis or any systemic antifungal with known activity against dermatophyte: 24 weeks
  3. 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