Tinea Pedis
Conditions
Keywords
Tinea pedis
Brief summary
To demonstrate comparable safety and efficacy of Taro Pharmaceuticals Inc. butenafine hydrochloride cream 1% (test product) and Lotrimin Ultra® cream (reference listed drug) in the treatment of interdigital tinea pedis, and to show the superiority of the active treatments over that of the placebo (vehicle).
Interventions
DRUGButenafine cream 1% manufactured by Taro
Treatment applied to affected area twice daily for 7 days
DRUGLotrimin Ultra (butenafine) 1%
Treatment applied to affected area twice daily for 7 days
DRUGButenafine Vehicle manufactured by Taro
Treatment applied to affected area twice daily for 7 days
Sponsors
Sun Pharmaceutical Industries, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Microbiologically confirmed clinical diagnosis of interdigital tinea pedis * If female and of child bearing potential, prepare to abstain from sexual intercourse or use a reliable method of contraception during the study (e.g., condom, intra-uterine device (IUD), oral, transdermal, injected or implanted hormonal contraceptives). * A confirmed clinical diagnosis of interdigital tinea pedis. Lesions are to be predominately interdigital but may extend to other areas of the foot (the non-interdigital lesions must not be hyperkeratotic). * The presence of tinea pedis infection, confirmed by the observation of segmented fungal hyphae during a microscopic potassium hydroxide (KOH) wet mount examination (potassium hydroxide mount preparation). * Identification of an appropriate dermatophyte by culture sent to the central laboratory. The appropriate dermatophytes are Trichophyton rubrum, Trichophyton mentagrophyte or Epidermophyton floccosum.
Exclusion criteria
* Use of any of the following within the indicated timeline: * Oral or injectable steroids * Any oral anti-fungals within 4 weeks of the study start * Use of topical corticosteroids or any other topical antipruritics on the feet within 72 hours of the study start. * Any prescription or over-the-counter (OTC) topical antifungals on the feet within two weeks prior to study entry * Use of any antihistamines within 72 hours of the study start. * Any known hypersensitivity to butenafine or other antifungal agents. * Evidence of any concurrent dermatophytic infection of toe nails (onychomycosis) or other dermatological condition of the foot that may interfere with the Investigator's evaluation of tinea pedis. * Patients with recurrent tinea pedis (more than 3 infections in the past 12 months) who have been unresponsive to previous antifungal therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Therapeutic Cure - Superiority Analysis | 42 days | Therapeutic Cure requires both Clinical Cure and Mycological Cure. Clinical Cure was based on the following signs and symptoms: fissuring, erythema, maceration, vesiculation, scaling, exudation, pruritus, burning. Each clinical symptom was evaluated using a 0-3 point rating scale: none=0, mild=1, moderate=2 or severe=3. If the score for erythema was ≤ 2 and the sum for all of the other 7 signs and symptoms was \<2 then the patient was considered a Clinical Cure. Mycological Cure: The potassium hydroxide (KOH) and the fungal culture were both negative. |
| Therapeutic Cure Non-Inferiority Comparison of Butenafine Cream and Lotrimin Ultra | 42 days | Patient was cured both by symptoms (Clinical Cure) and by the results of fungal testing (Mycological Cure). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Therapeutic Cure | 7 days | Subject with clinical and mycological cure at day 7 |
| Mycologic Cure | 42 days | Negative KOH and fungal culture at day 42 |
| Clinical Cure | 42 days | The following 8 signs and symptoms are rated at each visit: Erythema Fissuring Maceration Vesiculation Desquamation/scaling Exudation Pruritus Stinging/Burning Each symptom is evaluated using the following scale: 0 = None- Complete absence of any sign or symptom 1. = Mild - obvious but minimal involvement 2. = Moderate - something that is easily noted 3. = Severe - quite marked Clinical cure is defined as a score of 2 (moderate) or less for erythema and a total score for seven other signs and symptoms less than 2. |
| Safety and Adverse Event Profile | 42 days | — |
Countries
Belize, United States
Participant flow
Recruitment details
Patients 12 years of age and older, who presented with interdigital tinea pedis, with a positive potassium hydroxide test (KOH) and met the inclusion/exclusion criteria were enrolled in the trial. Subsequently samples were sent for culture to confirm that either T. rubrum, T. mentagrophytes, or E. floccosum were the causative organism.
Participants by arm
| Arm | Count |
|---|---|
| Butenafine Cream 1% (Taro) Butenafine cream manufactured by Taro applied for 7 days | 149 |
| Lotrimin Ultra (Butenafine) 1% Lotrimin Ultra (butenafine) applied for 7 days | 155 |
| Vehicle Butenafine vehicle applied for 7 days | 71 |
| Total | 375 |
Baseline characteristics
| Characteristic | Butenafine Cream 1% (Taro) | Lotrimin Ultra (Butenafine) 1% | Vehicle | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 6 Participants | 2 Participants | 12 Participants |
| Age, Categorical >=65 years | 10 Participants | 7 Participants | 3 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 135 Participants | 142 Participants | 66 Participants | 343 Participants |
| Region of Enrollment Belize | 26 participants | 20 participants | 9 participants | 55 participants |
| Region of Enrollment United States | 123 participants | 135 participants | 62 participants | 320 participants |
| Sex: Female, Male Female | 42 Participants | 41 Participants | 23 Participants | 106 Participants |
| Sex: Female, Male Male | 107 Participants | 114 Participants | 48 Participants | 269 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / — | 21 / — | 5 / — |
| serious Total, serious adverse events | 2 / — | 0 / — | 1 / — |
Outcome results
Primary
Therapeutic Cure Non-Inferiority Comparison of Butenafine Cream and Lotrimin Ultra
Patient was cured both by symptoms (Clinical Cure) and by the results of fungal testing (Mycological Cure).
Time frame: 42 days
Population: Patients with negative cultures excluded. Use per protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Butenafine Cream 1% (Taro) | Therapeutic Cure Non-Inferiority Comparison of Butenafine Cream and Lotrimin Ultra | 63 Participants |
| Lotrimin Ultra (Butenafine) 1% | Therapeutic Cure Non-Inferiority Comparison of Butenafine Cream and Lotrimin Ultra | 97 Participants |
90% CI: [-30.27, -9.29]
Primary
Therapeutic Cure - Superiority Analysis
Therapeutic Cure requires both Clinical Cure and Mycological Cure. Clinical Cure was based on the following signs and symptoms: fissuring, erythema, maceration, vesiculation, scaling, exudation, pruritus, burning. Each clinical symptom was evaluated using a 0-3 point rating scale: none=0, mild=1, moderate=2 or severe=3. If the score for erythema was ≤ 2 and the sum for all of the other 7 signs and symptoms was \<2 then the patient was considered a Clinical Cure. Mycological Cure: The potassium hydroxide (KOH) and the fungal culture were both negative.
Time frame: 42 days
Population: Patients with negative cultures at baseline are excluded. Efficacy ITT analysis includes all patients with positive baseline cultures, who received at least one dose of medication, had a follow-up visit and had data for the day 42 visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Butenafine Cream 1% (Taro) | Therapeutic Cure - Superiority Analysis | 76 Participants |
| Lotrimin Ultra (Butenafine) 1% | Therapeutic Cure - Superiority Analysis | 108 Participants |
| Vehicle | Therapeutic Cure - Superiority Analysis | 24 Participants |
p-value: 0.0127Fisher Exact
p-value: <0.0001Fisher Exact
Secondary
Clinical Cure
The following 8 signs and symptoms are rated at each visit: Erythema Fissuring Maceration Vesiculation Desquamation/scaling Exudation Pruritus Stinging/Burning Each symptom is evaluated using the following scale: 0 = None- Complete absence of any sign or symptom 1. = Mild - obvious but minimal involvement 2. = Moderate - something that is easily noted 3. = Severe - quite marked Clinical cure is defined as a score of 2 (moderate) or less for erythema and a total score for seven other signs and symptoms less than 2.
Time frame: 42 days
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Butenafine Cream 1% (Taro) | Clinical Cure | 83 Participants |
| Lotrimin Ultra (Butenafine) 1% | Clinical Cure | 111 Participants |
| Vehicle | Clinical Cure | 27 Participants |
Secondary
Mycologic Cure
Negative KOH and fungal culture at day 42
Time frame: 42 days
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Butenafine Cream 1% (Taro) | Mycologic Cure | 101 Participants |
| Lotrimin Ultra (Butenafine) 1% | Mycologic Cure | 128 Participants |
| Vehicle | Mycologic Cure | 33 Participants |
Secondary
Safety and Adverse Event Profile
Time frame: 42 days
Secondary
Therapeutic Cure
Subject with clinical and mycological cure at day 7
Time frame: 7 days
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Butenafine Cream 1% (Taro) | Therapeutic Cure | 30 Participants |
| Lotrimin Ultra (Butenafine) 1% | Therapeutic Cure | 38 Participants |
| Vehicle | Therapeutic Cure | 11 Participants |