Onychomycosis is a fungal infection of the toenail caused by a range of organisms, including dermophytes, non-dermophyte molds, and yeasts. Topical antifungals are often used for mild to moderate onychomycosis, especially when oral therapy is contraindicated. Generally, topical antifungal agents are well-tolerated with minimal side effects, but they are less effective than oral antifungal therapies due to poor nail penetration. Consequently, the current treatment period for topical onychomycosis products is \~12 months.
Terbinafine is an antifungal drug approved by the FDA for the treatment of topical skin infections. A new formulation (AP4500) has been developed to increase terbinafine absorption through the nail in order to directly kill fungi at the site of onychomycosis infection.
The goal of this clinical trial is to learn if AP4500 works to treat mild to moderate toenail fungus in adults. The main questions the study aims to answer are:
Does AP4500 work to treat onychomycosis? Does AP4500 work best when applied once or twice per day? Does AP4500 treat onychomycosis faster than current treatments? Is AP4500 more effective than current treatments?
Researchers will compare AP4500 to a vehicle control (a look-alike substance that contains no drug) and a commercial comparator product (Jublia) that has already been commercialized for the treatment of toenail fungus.
Participants will:
Apply topical formulations once or twice a day to an infected toenail for a period of 48 weeks Visit the clinic 4 times over this period for checkups and tests, with a subsequent follow up visit 4 weeks after treatment is completed
Male or female participants aged 18 to 70 years, inclusive at the time of informed consent.
In general, good health, as assessed by the Investigator, as determined by medical history, safety laboratory tests, and other tests.
At least 1 great toenail (the "target great toenail") with clinically diagnosed distal lateral subungual onychomycosis involving 20% to 50% of the affected great toenail but with no more than 6 toenails and no fingernails involved, and without dermatophytomas or lanula (matrix) involvement.
Target great toenail must have an uninfected length of at least 3 mm from the proximal nailfold and a thickness of no more than 3 mm.
Presence of any toenail infection other than or in addition to dermatophytes, such as Scytalidium as determined by the Investigator (candidal onychomycosis infection, concurrent with a positive dermatophyte culture, is acceptable).
Presence of any of the following: dermatophytoma, fungal "spikes" within 3 mm of the proximal toenail fold on the target great toenail, infection extending to the matrix, or only lateral toenail disease in the target great toenail.
Presence of severe moccasin tinea pedis at the Screening or Baseline visits, as determined by the Investigator. If the participant has interdigital tinea pedis that requires treatment, the participant must agree to use only an Investigator-approved topical antifungal therapy .
Presence of any disease/condition that might cause toenail abnormalities or may interfere with the evaluation of the investigational medicinal product (IMP), as determined by the Investigator (e.g., open sore or ulceration on the toes of affected toenails, psoriasis, immune dysfunction immunocompromised, collagen-vascular diseases, lichen planus, peripheral vascular disease, recurrent cellulitis, lymphatic insufficiency, or traumatic onychodystrophy due to chronic physical stimuli).