TDT 067 Onychomycosis Study

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to establish the efficacy, clinical benefits, and safety of treatment with TDT 067 for clinically diagnosed distal subungual onychomycosis of the toenails caused by dermatophytes confirmed by positive mycology.

Official Title
-----------------
A Randomized, Double-blind, Vehicle- and Placebo-Controlled, Multicenter Trial in Patients With Mild to Moderate Distal Subungual Toenail Onychomycosis to Investigate the Efficacy, Tolerability, and Safety of Twice Daily Application of TDT 067 for 48 Weeks

Conditions
-----------------
Onychomycosis

Intervention / Treatment
-----------------
* Drug: TDT067
* Drug: Placebo
* Drug: Transfersome


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must be between 18 and 75 years of age inclusive, of any race, and of either sex. Female patients must be either surgically sterile, postmenopausal (no menses for the previous 12 months), or must be practicing an effective method of birth control as determined by the Investigator. Patients must have at least 1 great toenail (target toenail) with clinically diagnosed distal subungual onychomycosis involving between 25% and 65%, inclusive, of the nail and confirmed by KOH visualization and fungal culture positive for dermatophytes. (Patients with culture positive for dermatophytes alone or dermatophytes and non dermatophytes are eligible to participate.) If both great toenails meet inclusion criteria, the one with the greater involvement will be designated the target nail. Patients must be able to understand the requirements of the study, abide by the restrictions, and return for all of the required examinations. Patients must be willing to sign a statement of informed consent. Patients must have a target great toenail with the capability to grow as determined by history of nail cutting. Patients must be willing to refrain from using any nail polish products and other nail cosmetic products on any of the toenails and must be willing to refrain from professional pedicures for the duration of this study. Exclusion Criteria: Patients who have been treated with an investigational drug within 1 month prior to study start. Patients who are pregnant or planning to become pregnant or who are lactating. Patients with hypersensitivity to terbinafine or to any other ingredients of the formulation. Patients who are unable to spray their toenails and the surrounding tissues on the affected foot without assistance. Patients with symptomatic tinea pedis requiring treatment. Patients using oral terbinafine within 6 months prior to the start of study; patients who have received other oral antifungals within 3 months. Patients using topical antifungal treatments for onychomycosis within 1 month prior to the start of study; patients using topical antifungal treatments for the feet within 1 month prior to the start of the study. Patients with any nail dystrophy that will interfere with the assessment of a clear nail. Patients who have toenail abnormalities or dystrophies that could prevent the restoration of a normal appearing nail in spite of a mycological cure for dermatophytes, including patients with psoriasis, lichen planus, malignancy or pigmentation disorders involving the nail unit, chemical damage, or onychodystrophy due to trauma or other structural deformities. Patients with superficial white or proximal subungual onychomycosis. Patients with a toenail infection involving a non dermatophyte alone. Patients with involvement of the matrix (lunula) or the proximal 2 mm of nail as measured from the proximal nail fold. Patients who have a nail plate with thickness greater than 2 mm or total thickness of the nail plus subungual debris measuring greater than 3 mm. Patients with yellow streaks or dermatophytoma of the target toenail. Patients with a history of peripheral arterial disease or diabetes mellitus. Patients with any condition that in the opinion of the Investigator renders the patient unsuitable for participation in this study. Patients with alanine aminotransferase (ALT) or aspartate (AST) levels greater than 2 times the upper limit of normal without clinical reason, unless, in the opinion of the Investigator, participation in this study would not place the patient at undue risk.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>non Transfersome® placebo | Drug: Placebo<br>* Study treatment (TDT 067, Transfersome® vehicle, or non Transfersome® placebo) will be applied twice a day for 48 weeks to the great toenail and the other nails and areas surrounding the nails on the foot. Each application will consist of 5 sprays: 1 spray each to the dorsal, medial, anterior, and frontal part of the great toe and a final spray applied evenly to the nail area of the remaining 4 toes. Patients will be instructed not to wash the treated foot or bathe for at least 4 hours after product application.<br>|
| Sham Comparator: Transfersome® vehicle<br>Transfersome® vehicle | Drug: Transfersome<br>* Study treatment (TDT 067, Transfersome® vehicle, or non Transfersome® placebo) will be applied twice a day for 48 weeks to the great toenail and the other nails and areas surrounding the nails on the foot. Each application will consist of 5 sprays: 1 spray each to the dorsal, medial, anterior, and frontal part of the great toe and a final spray applied evenly to the nail area of the remaining 4 toes. Patients will be instructed not to wash the treated foot or bathe for at least 4 hours after product application.<br>|
| Experimental: TDT 067<br>TDT 067 | Drug: TDT067<br>* Study treatment (TDT 067, Transfersome® vehicle, or non Transfersome® placebo) will be applied twice a day for 48 weeks to the great toenail and the other nails and areas surrounding the nails on the foot. Each application will consist of 5 sprays: 1 spray each to the dorsal, medial, anterior, and frontal part of the great toe and a final spray applied evenly to the nail area of the remaining 4 toes. Patients will be instructed not to wash the treated foot or bathe for at least 4 hours after product application.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure Rate | To compare complete cure rates for onychomycosis at Week 52 for TDT 067 versus non-Transfersome placebo. If the comparison between TDT 067 and non-Transfersome placebo is statistically significant in favor of TDT 067, the following additional primary efficacy objective: To compare onychomycosis cure rates at Week 52 for TDT 067 versus Transfersome vehicle | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure Rate 48 | Compare onychomycosis complete cure rates at Wk 48 for TDT 067 versus non Transfersome® placebo and Transfersome® vehicle Compare effective treatment rates at Wk 48 for TDT 067 versus non Transfersome® placebo and Transfersome® vehicle Compare mycological cure rates at Wk 48 for TDT 067 versus non Transfersome® placebo and Transfersome® vehicle Compare complete cure rates at Wk 48 effective treatment rates at Wks 48, and mycological cure rates at Wks 48 for Transfersome® vehicle versus non Transfersome® placebo | 48 Weeks | 
| Cure Rate 52 | Compare onychomycosis complete cure rates at Wk 52 for TDT 067 versus non Transfersome® placebo and Transfersome® vehicle Compare effective treatment rates at Wk 52 for TDT 067 versus non Transfersome® placebo and Transfersome® vehicle Compare mycological cure rates at Wk 52 for TDT 067 versus non Transfersome® placebo and Transfersome® vehicle Compare complete cure rates at Wk 52 effective treatment rates at Wk 52 and mycological cure rates at Wk 52 for Transfersome® vehicle versus non Transfersome® placebo | 52 Weeks | 
| Cure Rate 60 | Compare onychomycosis complete cure rates at Wk 60 for TDT 067 versus non Transfersome® placebo and Transfersome® vehicle Compare effective treatment rates at Wk 60 for TDT 067 versus non Transfersome® placebo and Transfersome® vehicle Compare mycological cure rates at Wk 60 for TDT 067 versus non Transfersome® placebo and Transfersome® vehicle Compare complete cure rates at Wk 60, effective treatment rates at Wk 60, and mycological cure rates at Wk 60 for Transfersome® vehicle versus non Transfersome® placebo | 60 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Distal Subungual Toenail Onychomycosis