Athlete's Foot, Tinea Pedis
Conditions
Keywords
Tinea Pedis, Athlete's foot
Brief summary
A research study to compare the safety and effectiveness of an investigational medication called NAFT-500 to placebo, when used in subjects with tinea pedis (athlete's foot).
Detailed description
To evaluate the efficacy and safety of NAFT-500 compared to placebo in the treatment of subjects with potassium hydroxide (KOH) and culture positive symptomatic tinea pedis.
Interventions
DRUGNAFT-500
topical cream 1 application every day up to 4 weeks weeks
DRUGPlacebo 2-weeks
placebo cream 1 application every day for up to 4 weeks
DRUGNaftin 1%
topical allylamine cream applied once a day for up to 4 weeks
DRUGPlacebo 4-weeks
topical placebo cream applied once a day for up to 4 weeks
Sponsors
Merz North America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Review and sign a statement of Informed Consent and HIPAA authorization. 2. For minors (less than 18 years), the parent/legal guardian must complete the informed consent process AND the subject must complete the assent process and sign the appropriate form (if age appropriate). 3. Males or non-pregnant females ≥12 years of age, of any race or sex. Females of childbearing potential must have a negative urine pregnancy test. 4. Presence of tinea pedis on one or both feet characterized by clinical evidence of a tinea infection (at least moderate erythema, moderate scaling, and mild pruritus)based on signs and symptoms. 5. KOH positive and culture positive baseline skin scrapings obtained from the site most severely affected or a representative site of the overall severity. 6. Subjects must be in good health and free from any clinically significant disease that might interfere with the study evaluations. 7. Subject must be able to understand the requirements of the study and willing to comply with the study requirements.
Exclusion criteria
1. A life-threatening condition (ex. autoimmune deficiency syndrome, cancer, unstable angina, or myocardial infarction) within the last 6 months. 2. Subjects with abnormal findings - physical or laboratory - that are considered by the investigator to be clinically important and indicative of conditions that might complicate interpretation of study results. 3. Subjects with a known hypersensitivity to study medications or their components. 4. Subjects who have a recent history or who are currently known to abuse alcohol or drugs. 5. Uncontrolled diabetes mellitus. 6. Hemodialysis or chronic ambulatory peritoneal dialysis therapy. 7. Current diagnosis of immunocompromising conditions. 8. Foot psoriasis, corns and/or callus involving any web spaces, atopic or contact dermatitis. 9. Severe dermatophytoses, onychomycosis (on the evaluated foot), mucocutaneous candidiasis, or bacterial skin infection. 10. Extremely severe tinea pedis (incapacitating). 11. Female subject who is pregnant or lactating, who is not using or does not agree to use an acceptable form of contraception during the study, or who intends to become pregnant during the study (females who are surgically sterilized or post menopausal for at least 2 years are not considered to be of childbearing potential).For the purposes of this study, acceptable forms of birth control include: oral contraceptives, contraceptive patches/implants, double barrier methods (e.g., use of condom and spermicide), IUD, and abstinence with second acceptable method should subject become sexually active. 12. Subjects using the following medications: * Topical anti-fungal therapy, foot/shoe powders, or topical corticosteroids applied to the feet within 14 days prior to randomization. Topical terbinafine, butenafine,and naftifine within 30 days prior to randomization * Oral anti-fungal therapies 3 months (8 months for oral terbinafine) prior to randomization * Systemic antibiotic or corticosteroid treatment within 30 days of randomization * Any other significant treatments, except hormonal contraception and multivitamin, at the discretion of the investigator that would interfere with study treatment. * Investigational drug within 30 days of randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Complete Cure at Week 6. | Week 6 | The first primary efficacy variable was the percentage of subjects in the NAFT-500 Cream, 2% or 2-week placebo groups with complete cure at Week 6. The second primary efficacy variable was the percentage of subjects in the Naftin 1% Cream or 4-week placebo groups with complete cure at Week 6. Complete cure was defined as negative mycology results from the central laboratory (dermatophyte culture and KOH) and absence of erythema, scaling, and pruritus that were evaluated using a 4 point severity scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Mycological Cure and Percentage of Subjects With Treatment Effectiveness at Week 6 | Week 6 | Mycological Cure was defined as negative KOH result and negative dermatophyte culture at Week 6. Treatment Effectiveness was defined as negative KOH, negative culture, and Scaling, Erythema, and Pruritus grades of 0 or 1 at Week 6. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NAFT-500 Naftin 2% Cream applied daily for 2 weeks | 234 |
| Placebo 2-wks Placebo applied daily for 2-weeks | 118 |
| Naftin 1% Naftin 1% active comparator applied daily for 4 weeks | 236 |
| Placebo 4-wks Placebo cream applied daily for 4 weeks | 119 |
| Total | 707 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 | 1 |
| Overall Study | Lost to Follow-up | 17 | 12 | 15 | 6 |
| Overall Study | Non-compliance | 1 | 0 | 1 | 3 |
| Overall Study | Non-specific | 62 | 42 | 79 | 33 |
| Overall Study | Physician Decision | 1 | 1 | 0 | 0 |
| Overall Study | Termination by sponsor | 4 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 6 | 2 |
Baseline characteristics
| Characteristic | Placebo 2-wks | Naftin 1% | NAFT-500 | Placebo 4-wks | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 14 Participants | 2 Participants | 6 Participants | 23 Participants |
| Age, Categorical >=65 years | 2 Participants | 10 Participants | 12 Participants | 2 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 115 Participants | 212 Participants | 220 Participants | 111 Participants | 658 Participants |
| Age Continuous | 41.0 years STANDARD_DEVIATION 12.91 | 41.4 years STANDARD_DEVIATION 14.08 | 42.7 years STANDARD_DEVIATION 13.03 | 41.4 years STANDARD_DEVIATION 14 | 41.7 years STANDARD_DEVIATION 13.52 |
| Region of Enrollment United States | 118 participants | 236 participants | 234 participants | 119 participants | 707 participants |
| Sex: Female, Male Female | 38 Participants | 71 Participants | 63 Participants | 33 Participants | 205 Participants |
| Sex: Female, Male Male | 80 Participants | 165 Participants | 171 Participants | 86 Participants | 502 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 38 / 234 | 22 / 118 | 31 / 236 | 26 / 119 |
| serious Total, serious adverse events | 0 / 234 | 0 / 118 | 1 / 236 | 0 / 119 |
Outcome results
Primary
Percentage of Subjects With Complete Cure at Week 6.
The first primary efficacy variable was the percentage of subjects in the NAFT-500 Cream, 2% or 2-week placebo groups with complete cure at Week 6. The second primary efficacy variable was the percentage of subjects in the Naftin 1% Cream or 4-week placebo groups with complete cure at Week 6. Complete cure was defined as negative mycology results from the central laboratory (dermatophyte culture and KOH) and absence of erythema, scaling, and pruritus that were evaluated using a 4 point severity scale.
Time frame: Week 6
Population: This is based on the Full Analysis Set (FAS). The FAS is the subset of all subjects in the Safety Evaluation Set (SES) with a positive culture at baseline for whom the primary efficacy variable is available. This is a modified intent to treat (MITT) principle because the culture results will not be available before the start of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NAFT-500 | Percentage of Subjects With Complete Cure at Week 6. | 17.7 percentage of subjects with complete cur |
| Placebo 2-weeks | Percentage of Subjects With Complete Cure at Week 6. | 7.1 percentage of subjects with complete cur |
| Naftin 1% | Percentage of Subjects With Complete Cure at Week 6. | 16.1 percentage of subjects with complete cur |
| Placebo 4-wks | Percentage of Subjects With Complete Cure at Week 6. | 3.1 percentage of subjects with complete cur |
Comparison: The first primary efficacy hypotheses tests are:~H01: p1 ≤ p01 vs. H1: p1 \> p01 where p01 and p1 denote the proportions of complete cure in the placebo 2wks and NAFT-500 groups, respectively.p-value: 0.01Cochran-Mantel-Haenszel
Comparison: The second primary efficacy hypotheses tests are:~H02: p2 ≤ P02 vs. H2: P2 \> p02 where p02 and p2 are denote proportions of complete cure in the placebo 4wks and Naftin 1% groups, respectivelyp-value: 0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects With Mycological Cure and Percentage of Subjects With Treatment Effectiveness at Week 6
Mycological Cure was defined as negative KOH result and negative dermatophyte culture at Week 6. Treatment Effectiveness was defined as negative KOH, negative culture, and Scaling, Erythema, and Pruritus grades of 0 or 1 at Week 6.
Time frame: Week 6
Population: This was the Full Analysis Set (FAS) comprising of subjects in the Safety Evaluation Set (SES) with a positive culture at baseline for whom the primary efficacy variable was available. This was a Modified Intent to Treat (MITT) principle because the culture results were not available at the start of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NAFT-500 | Percentage of Subjects With Mycological Cure and Percentage of Subjects With Treatment Effectiveness at Week 6 | Mycological Cure (MC) | 67.3 percentage of Subjects |
| NAFT-500 | Percentage of Subjects With Mycological Cure and Percentage of Subjects With Treatment Effectiveness at Week 6 | Treatment Effectiveness (TE) | 56.5 percentage of Subjects |
| Placebo 2-weeks | Percentage of Subjects With Mycological Cure and Percentage of Subjects With Treatment Effectiveness at Week 6 | Treatment Effectiveness (TE) | 20.0 percentage of Subjects |
| Placebo 2-weeks | Percentage of Subjects With Mycological Cure and Percentage of Subjects With Treatment Effectiveness at Week 6 | Mycological Cure (MC) | 21.4 percentage of Subjects |
| Naftin 1% | Percentage of Subjects With Mycological Cure and Percentage of Subjects With Treatment Effectiveness at Week 6 | Mycological Cure (MC) | 71.3 percentage of Subjects |
| Naftin 1% | Percentage of Subjects With Mycological Cure and Percentage of Subjects With Treatment Effectiveness at Week 6 | Treatment Effectiveness (TE) | 58.7 percentage of Subjects |
| Placebo 4-wks | Percentage of Subjects With Mycological Cure and Percentage of Subjects With Treatment Effectiveness at Week 6 | Mycological Cure (MC) | 21.5 percentage of Subjects |
| Placebo 4-wks | Percentage of Subjects With Mycological Cure and Percentage of Subjects With Treatment Effectiveness at Week 6 | Treatment Effectiveness (TE) | 13.8 percentage of Subjects |