Safety and Efficacy Study of Subjects With Onychomycosis of the Great Toenail

An Open-Label, Rising Multiple-Dose, Multi-Center Study to Evaluate the Safety and Efficacy of Topically Applied AN2690 5.0% and 7.5% Solution for the Treatment of Adult Subjects With Onychomycosis of the Great Toenail

The purpose of the study is to determine the safety and efficacy of 5.0% and 7.5% AN2690 Solution in the treatment of distal, subungual onychomycosis of the great target toenail.

The first group of 30 protocol-qualified subjects will be assigned to Treatment Group 1 and given 5% AN2690 Solution. Provided that there is adequate evidence of clinical safety after two weeks of dosing with 5% AN2690 Solution, a second group of 30 protocol-qualified subjects will be assigned to Treatment Group 2 and given 7.5% AN2690 Solution. A third group of 30 subjects will be enrolled and assigned the highest safe concentration of AN2690 evaluated in this study.

Inclusion Criteria:

1. Witnessed, signed informed consent approved by Ethics Committee
2. Male or female subjects of any race at least 18 years of age but not older than 65 years of age at the time of screening
3. Subjects with a diagnosis of onychomycosis of at least one great toenail and with a positive KOH wet mount from that nail
4. Onychomycosis involving 20-60% of the affected great toenail as determined by visual inspection after the nail has been trimmed
5. The combined thickness of the distal nail plate and the associated hyperkeratotic nail bed <3 mm
6. Affected great toenail to be treated is capable of re-growth as documented by history or recent observation of at least 2 mm of growth
7. Normal or not clinically significant screening safety labs

Exclusion Criteria:

1. Females of childbearing potential not using a highly effective method of birth control (e.g. implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices) during the study

2. Diabetes mellitus requiring treatment other than diet and exercise

3. Subjects with chronic moccasin type of T. pedis

4. Subjects with a history of having failed any previous topical antifungal therapy for their onychomycosis

5. Subjects unwilling 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.

6. Subjects that have not undergone the specified washout period(s) for the following topical preparations or subjects who require the concurrent use of any of the following topical medications:

   • 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

7. Subjects that have not undergone the specified washout period(s) for the following systemic medications or subjects who require the concurrent use of any of the following systemic medications:

   • Corticosteroids (including intramuscular injections): 2 weeks
   • Antifungals for treatment of onychomycosis or any systemic antifungal with known activity against dermatophytes: 24 weeks
   • Systemic immunomodulators: 4 weeks

8. Treatment of any type for cancer within the last 6 months

9. History of any significant internal disease

10. Subjects with a medical history of current or past psoriasis of the skin and/or nails

11. Concurrent lichen planus

12. Subjects who are known to be allergic to any of the test product(s) 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

13. Nail or anatomic abnormalities of the toe, e.g., genetic nail disorders, primentary disorders, onychogryphosis, trauma to the nail(s) to be treated

14. AIDS or AIDS related complex

15. History of street drug or alcohol abuse

16. Any subject not able to meet the study attendance requirements

17. Subjects who have participated in any other trial of an investigational drug or device within 60 days prior to enrollment or participation in a research study concurrent with this study