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CompletedNCT00835510Updated Feb 4, 2014Results posted

Clinical Equivalence of Two Butenafine Hydrochloride 1% Creams in Patients With Interdigital Tinea Pedis

A Phase 1 interventional study of Butenafine cream 1% manufactured by Taro and Lotrimin Ultra (butenafine) 1% in Tinea Pedis, sponsored by Taro Pharmaceuticals USA. Completed at 17 sites in 2 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2014-02-04.

Sponsored by Taro Pharmaceuticals USA · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
548
Allocation
Randomized
Ages
12 Years and older
Sex
All
01

Study 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).

02

Conditions studied

  • Tinea Pedis

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Keywords

  • Tinea pedis
03

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
548 participants (actual)

Study arms

  • Experimental
    Butenafine cream 1% (Taro)

    Butenafine cream manufactured by Taro applied for 7 days

    Drug: Butenafine cream 1% manufactured by Taro

  • Active comparator
    Lotrimin Ultra (butenafine) 1%

    Lotrimin Ultra (butenafine) applied for 7 days

    Drug: Lotrimin Ultra (butenafine) 1%

  • Placebo comparator
    Vehicle

    Butenafine vehicle applied for 7 days

    Drug: Butenafine Vehicle manufactured by Taro

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

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. Therapeutic Cure

    Subject with clinical and mycological cure at day 7

    Time frame: 7 days

  2. Mycologic Cure

    Negative KOH and fungal culture at day 42

    Time frame: 42 days

  3. 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

  4. Safety and Adverse Event Profile

    Time frame: 42 days

06

Results

Posted Oct 6, 2009

Participant flow

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.

Participant flow — Overall Study
MilestoneButenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%Vehicle
Started219221108
Positive fungal culture14915571
Completed14315270
Not completed766938

Outcome measures

PrimaryTherapeutic 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
Reported as:
Number · Participants
Therapeutic Cure - Superiority Analysis
ParticipantsButenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%Vehicle
Therapeutic Cure - Superiority Analysis7610824
Statistical analysis
  • Butenafine Cream 1% (Taro) vs Vehicle · Fisher Exact · p = 0.0127two-sided
  • Lotrimin Ultra (Butenafine) 1% vs Vehicle · Fisher Exact · p = <0.0001two-sided
SecondaryTherapeutic Cure

Subject with clinical and mycological cure at day 7

Time frame:
7 days
Reported as:
Number · Participants
Therapeutic Cure
ParticipantsButenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%Vehicle
Therapeutic Cure303811
SecondaryMycologic Cure

Negative KOH and fungal culture at day 42

Time frame:
42 days
Reported as:
Number · Participants
Mycologic Cure
ParticipantsButenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%Vehicle
Mycologic Cure10112833
SecondaryClinical 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
Reported as:
Number · Participants
Clinical Cure
ParticipantsButenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%Vehicle
Clinical Cure8311127
SecondarySafety and Adverse Event Profile
Time frame:
42 days

Results for this outcome have not been posted.

PrimaryTherapeutic 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
Reported as:
Number · Participants
Therapeutic Cure Non-Inferiority Comparison of Butenafine Cream and Lotrimin Ultra
ParticipantsButenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%Vehicle
Therapeutic Cure Non-Inferiority Comparison of Butenafine Cream and Lotrimin Ultra6397—
Statistical analysis
  • Butenafine Cream 1% (Taro) vs Lotrimin Ultra (Butenafine) 1% · Cure rate difference: -19.78 · 90% CI -30.27 to -9.29

Adverse events

Collected over Adverse event data was collected over the 42 day duration of the study.. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Butenafine Cream 1% (Taro)———
Lotrimin Ultra (Butenafine) 1%———
Vehicle———
Most frequent serious events
Most frequent serious events
EventButenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%Vehicle
CellulitisInfections and infestations1/2190/2211/108
TachycardiaCardiac disorders1/2190/2210/108
Most frequent other events
Most frequent other events
EventButenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%Vehicle
HeadacheNervous system disorders10/21916/2214/108
NasopharyngitisInfections and infestations4/2195/2211/108

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Butenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%VehicleTotal
<=18 years46212
Between 18 and 65 years13514266343
>=65 years107320
Sex: Female, Male
Sex: Female, Male(Participants)Butenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%VehicleTotal
Female424123106
Male10711448269
Region of Enrollment
Region of Enrollment(participants)Butenafine Cream 1% (Taro)Lotrimin Ultra (Butenafine) 1%VehicleTotal
United States12313562320
Belize2620955
07

Study locations

17 sites
  • Investigator Site
    Burbank, California, United States
  • Investigator Site
    San Diego, California, United States
  • Investigator Site
    Miami, Florida, United States
  • Investigator Site
    Martinez, Georgia, United States
  • Investigator Site
    Stockbridge, Georgia, United States
  • Investigator Site
    Clinton Township, Michigan, United States
  • Investigator Site
    Hickory, North Carolina, United States
  • Investigator Site
    Raleigh, North Carolina, United States
  • Investigator Site
    Salisbury, North Carolina, United States
  • Investigator Site
    Sylvania, Ohio, United States
  • Investigator Site
    Simpsonville, South Carolina, United States
  • Investigator Site
    Bristol, Tennessee, United States
  • Investigator Site
    Nashville, Tennessee, United States
  • Investigator Site
    College Station, Texas, United States
  • Investigator Site
    Houston, Texas, United States
  • Investigator Site
    San Antonio, Texas, United States
  • Investigator Site
    Belize City, Belize
08

Registry details

Key details

Study ID
NCT00835510
Lead sponsor
Taro Pharmaceuticals USA
Responsible party
Sponsor
First posted
Feb 3, 2009
Start date
Jun 2008
Primary completion
Oct 2008
Completion
Dec 2008
Results posted
Oct 6, 2009
Last update
Feb 4, 2014

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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