Tinea Pedis
Conditions
Keywords
Tinea Pedis, Ketoconazole (NIZORAL), Antifungal Agents, Miconazole (DAKTARIN)
Brief summary
The purpose of this study is to determine if a new formulation of ketoconazole 2% cream is as effective as a current formulation of ketoconazole 2% cream (Nizoral) compared with placebo in treating patients with Tinea pedis, a skin infection commonly known as athlete's foot that is caused by a kind of mold called a fungus.
Detailed description
This is a randomized (study drug assigned by chance), double-blind (neither the physician nor the patient knows the name of the assigned treatment), multicentre study in Poland and the United Kingdom designed to assess the mycological (fungal) cure rate and clinical efficacy of a new formulation of ketoconazole 2% cream (F126) with the current formulation of ketoconazole 2% cream (Nizoral) (F012) compared with placebo cream in patients with symptomatic uncomplicated interdigital (between the toes) Tinea pedis, a skin infection commonly known as athlete's foot that is caused by a kind of mold called a fungus. Approximately 548 patients who have symptomatic uncomplicated interdigital Tinea pedis confirmed by positive potassium hydroxide (KOH) microscopy (examination using a microscope) and mycological (fungal) culture will be randomized to receive 1 of 2 formulations of ketoconazole 2% cream (formulation F012 or F126) or placebo cream. There will be 4 study visits during the study. At Visit 1 (baseline), patients will sign the informed consent and be assessed for mycological and clinical signs and symptoms of Tinea pedis. Baseline demographics (age, race, etc), medical history and medication (s) that the patient is currently taking will be recorded. Patients will be issued with a tube of the cream and instructed to apply the cream sparingly to all affected areas of the foot (or feet), once daily (at night or in the evenings) for a total of 4 weeks according to protocol-specified guidelines. During the 4-week treatment period patients will return to the study every 2 weeks to be assessed for clinical signs and symptoms. After the 4-week treatment period, patients will continue participation in the study for an additional 2 weeks without medication. Patients will return then return to the study center for a final visit (Visit 4, Week 6) at which time skin scrapings will be sampled from interdigital spaces on both feet for KOH microscopy and mycological culture. The primary efficacy endpoint is to determine whether a new formulation of ketoconazole 2% cream is equivalent (or as effective) as the current formulation of ketoconazole 2% cream (Nizoral) compared to a placebo cream in achieving a mycological cure (defined as negative KOH microscopy and negative mycological culture) following 4 weeks of treatment. The primary outcome measure in the study is a mycological cure (defined as negative KOH microscopy and negative mycological culture) at week 6. Patients will be monitored for safety (occurrence of adverse events, use of concomitant medications, and reasons for premature discontinuation from the study) from Visit 1 through Visit 4 (Week 6 or time of early termination from study). Patients will be provided with up to two 15g tubes of ketoconazole cream (formulation F126 or F012) or matching placebo cream and be instructed to apply cream sparingly to affected areas of the feet once daily at night or in the evening for 4 weeks according to protocol specified guidelines.
Interventions
DRUGPlacebo cream
A topical, white, homogenous cream identical in appearance to study drug applied sparingly to all affected areas of the foot (or feet), once daily (at night or in the evenings) for a total of 4 weeks.
DRUGKetoconazole 2% cream (formulation F012) (Nizoral)
A topical, white, homogenous cream containing the equivalent of 20 mg (or 2%) of ketoconazole identical in appearance to study drug applied sparingly to all affected areas of the foot (or feet), once daily (at night or in the evenings) for a total of 4 weeks.
DRUGKetoconazole 2% cream (formulation F126)
A topical, white, homogenous cream containing the equivalent of 20 mg (or 2%) of ketoconazole applied sparingly to all affected areas of the foot (or feet), once daily (at night or in the evenings) for a total of 4 weeks.
Sponsors
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be co-operative, reliable and sufficiently competent to grade and record symptoms as requested * have a clinical diagnosis of uncomplicated interdigital Tinea pedis confirmed by KOH microscopy * Be either post-menopausal or surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before entry and throughout the study and have a negative urine pregnancy test at screening (applies to women only) * Sign an informed consent form indicating an understanding of the purpose of and procedures required for the study and willingness to participate in the study
Exclusion criteria
* Have complicated Tinea pedis defined as confluent, diffuse moccasin type tinea pedis of the entire plantar surface (undersurface of foot), onychomycosis (fungal nail infection) * other dermatomycosis (fungal skin infection) requiring active treatment * Have a previous sensitivity to imidazole antifungal agents or to any ingredient of the study medication * Have a history of disallowed therapies including oral (by mouth) antifungal treatments within the previous 6 weeks, recent use (within 2 weeks of the study start) of topical antifungal agent, immunosuppressive or radiation therapy within the previous 4 weeks, recent use (within 2 weeks prior to screening) of other oral antibiotics, systemic corticosteroids or topical corticosteroids or antibiotics applied to the feet * Be HIV-positive (testing will not be performed) * Have uncontrolled diabetes mellitus or peripheral vascular disease requiring active treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients in the Positive Baseline Culture Set (PBCS) With Mycological Cure (MC) at Week 6 | Week 6 | Mycological Cure (MC) was defined as having a negative potassium hydroxide (KOH) microscopy and negative fungal culture at Week 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients in the Positive Baseline Culture Set (PBCS) With Overall Cure (OC) at Week 6 | Week 6 | Overall Cure (OC) was defined as Mycological Cure (MC) in addition to a global clinical evaluation of either 'Completely Cleared' (clearance of all signs and symptoms of Tinea pedis) or 'Marked Improvement' (significant improvement of signs and symptoms of Tinea pedis; residual signs and symptoms only), assessed at Week 6. |
Countries
Poland, United Kingdom
Participant flow
Pre-assignment details
All randomized patients (583) received at least one dose of study treatment and were included in the Safety Set. Only patients who had a positive Tinea pedis culture at baseline, ie 281 patients, were included in the Positive Baseline Culture Set (PBCS), which was the set used for analysis of the Primary and Secondary Outcome Measures.
Participants by arm
| Arm | Count |
|---|---|
| Placebo A topical white homogenous cream identical in appearance to study drug | 119 |
| Nizoral Ketoconazole 2% cream (formulation F012) (Nizoral) | 230 |
| Ketoconazole Ketoconazole 2% cream (formulation F126) | 234 |
| Total | 583 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 | 3 |
| Overall Study | Lack of Efficacy | 3 | 1 | 1 |
| Overall Study | Lost to Follow-up | 9 | 10 | 15 |
| Overall Study | Other | 1 | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 6 | 2 |
Baseline characteristics
| Characteristic | Nizoral | Ketoconazole | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Age, Categorical >=65 years | 21 Participants | 25 Participants | 9 Participants | 55 Participants |
| Age, Categorical Between 18 and 65 years | 207 Participants | 209 Participants | 109 Participants | 525 Participants |
| Age, Continuous | 45 years STANDARD_DEVIATION 13.94 | 45.9 years STANDARD_DEVIATION 14.62 | 43.2 years STANDARD_DEVIATION 14.89 | 45 years STANDARD_DEVIATION 14.42 |
| Baseline BMI | 27.9 kg/m2 STANDARD_DEVIATION 4.76 | 28.3 kg/m2 STANDARD_DEVIATION 5.09 | 28.1 kg/m2 STANDARD_DEVIATION 5.81 | 28.1 kg/m2 STANDARD_DEVIATION 5.11 |
| Sex: Female, Male Female | 71 Participants | 61 Participants | 29 Participants | 161 Participants |
| Sex: Female, Male Male | 159 Participants | 173 Participants | 90 Participants | 422 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 | 55 / 234 | 50 / 230 | 28 / 119 |
| serious Total, serious adverse events | 2 / 234 | 5 / 230 | 2 / 119 |
Outcome results
Primary
The Number of Patients in the Positive Baseline Culture Set (PBCS) With Mycological Cure (MC) at Week 6
Mycological Cure (MC) was defined as having a negative potassium hydroxide (KOH) microscopy and negative fungal culture at Week 6.
Time frame: Week 6
Population: Only patients who had a positive Tinea pedis culture at baseline, ie 281 patients, were included in the Positive Baseline Culture Set (PBCS), which was the set used for analysis of the Primary Outcome Measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Number of Patients in the Positive Baseline Culture Set (PBCS) With Mycological Cure (MC) at Week 6 | 11 participants |
| Nizoral | The Number of Patients in the Positive Baseline Culture Set (PBCS) With Mycological Cure (MC) at Week 6 | 64 participants |
| Ketoconazole | The Number of Patients in the Positive Baseline Culture Set (PBCS) With Mycological Cure (MC) at Week 6 | 64 participants |
Secondary
The Number of Patients in the Positive Baseline Culture Set (PBCS) With Overall Cure (OC) at Week 6
Overall Cure (OC) was defined as Mycological Cure (MC) in addition to a global clinical evaluation of either 'Completely Cleared' (clearance of all signs and symptoms of Tinea pedis) or 'Marked Improvement' (significant improvement of signs and symptoms of Tinea pedis; residual signs and symptoms only), assessed at Week 6.
Time frame: Week 6
Population: Only patients who had a positive Tinea pedis culture at baseline, ie 281 patients, were included in the Positive Baseline Culture Set (PBCS), which was the set used for analysis of the Secondary Outcome Measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Number of Patients in the Positive Baseline Culture Set (PBCS) With Overall Cure (OC) at Week 6 | 5 participants |
| Nizoral | The Number of Patients in the Positive Baseline Culture Set (PBCS) With Overall Cure (OC) at Week 6 | 55 participants |
| Ketoconazole | The Number of Patients in the Positive Baseline Culture Set (PBCS) With Overall Cure (OC) at Week 6 | 50 participants |