Tinea Pedis
Conditions
Brief summary
Clinical Study to Evaluate the Therapeutic Equivalence of Ketoconazole Cream 2% in the Treatment of Tinea Pedis
Detailed description
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site Clinical Study to Evaluate the Therapeutic Equivalence of Ketoconazole Cream 2% (Encube Ethicals Pvt Ltd) to Ketoconazole Cream 2% (G&W Laboratories Inc.) in the Treatment of Tinea Pedis
Interventions
DRUGKetoconazole Cream 2%
Patients will be instructed to apply sufficient study product to cover affected and immediate surrounding areas once daily for 42 ± 4 days. Each patient is expected to receive 42 ± 4 doses.
DRUGKetoconazole Cream 2% (G&W Laboratories Inc.)
Patients will be instructed to apply sufficient study product to cover affected and immediate surrounding areas once daily for 42 ± 4 days. Each patient is expected to receive 42 ± 4 doses.
DRUGPlacebo
Patients will be instructed to apply sufficient study product to cover affected and immediate surrounding areas once daily for 42 ± 4 days. Each patient is expected to receive 42 ± 4 doses.
Sponsors
Novum Pharmaceutical Research Services
ACM Global Laboratories
Encube Ethicals Pvt. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All study products are blinded and provided to the patients in the same packaging.
Intervention model description
Randomized, double-blind, placebo-controlled, three-arm, parallel group, multiple-site bioequivalence study with clinical endpoints.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Healthy male or non-pregnant, non-lactating female, ≥ 18 years of age. 2. Signed informed consent form (ICF) that meets all criteria of current Food and Drug Administration regulations. 3. Female patient of childbearing potential must not be pregnant or lactating at Visit 1 (as confirmed by a negative urine pregnancy test with a sensitivity of less than 50 milli-International unit (mIU/mL) or equivalent units of human chorionic gonadotropin). 4. Female patient of childbearing potential must agree to the use of a reliable method of contraception throughout the study (e.g., total abstinence, intrauterine device, a double-barrier method, oral, transdermal, injected, or implanted non-hormonal or hormonal contraceptive) throughout the study. A sterile sexual partner is not considered an adequate form of birth control. If the female is using any estrogen or oral contraceptive therapy, the same product must have been taken for at least one month before Visit 1. 5. Have clinical diagnosis of tinea pedis with lesions localized to the interdigital spaces or predominantly interdigital, but may extend to other areas of the foot (the non-interdigital lesions should not be hyperkeratotic, i.e., characteristic of tinea pedis moccasin). 6. The presence of tinea pedis infection provisionally confirmed at baseline by a positive potassium hydroxide (KOH) wet mount preparation (i.e., skin scrapings from the target site are placed on a microscope slide with a drop of 10% KOH, and microscopic examination reveals segmented fungal hyphae). 7. The sum of clinical signs and symptoms scores of the target lesion ≥ 4. See Appendix A for scoring scale: 1. Signs: Fissuring/cracking, erythema, maceration and scaling 2. Symptoms: pruritus and burning/stinging In addition the target lesion must have a minimum score ≥ 2 for erythema and a minimum score ≥ 2 for either pruritus or scaling.
Exclusion criteria
1. Females who are pregnant, lactating or planning to become pregnant during the study period. 2. History of or current psoriasis, Lichen planus or contact dermatitis involving the feet within the previous 12 months. 3. History of dermatophyte infections with a lack of response to antifungal therapy (recurrent tinea pedis \[i.e., more than 3 infections in the past 12 months\] that were unresponsive to previous antifungal therapy). 4. History of allergy, hypersensitivity, or intolerance to ketoconazole, other imidazoles, sulfites or any other component of the study product. 5. Confluent, diffuse moccasin-type tinea pedis of the entire plantar surface. 6. Current uncontrolled diabetes. 7. Presence of any other infection of the foot or other disease process that, in the Investigator's opinion, may interfere with the evaluation of the patient's tinea pedis. 8. Known history of or current impaired wound healing, presence of peripheral vascular disease and/or trophic changes of the lower limbs to an extent that, in the opinion of the Investigator, would make the patient unsuitable for the study or compromise patient's safety. 9. Significant history or current evidence of chronic infectious disease, system disorder, organ disorder, immunosuppression (due to disease or therapy, including history of organ transplant), or other medical condition that, in the Investigator's opinion, would place the patient at undue risk by participating or compromise the integrity of the study data. 10. Use of antipruritics, including antihistamines, within 72 hours before Visit 1. 11. Use of topical corticosteroids, topical antibiotics or topical antifungal therapy (e.g., clotrimazole, econazole, fluconazole) within 2 weeks before Visit 1. 12. Use of systemic (e.g., oral or injectable) antibiotics, systemic antifungal therapy, or systemic corticosteroids within 30 days before Visit 1. The use of intranasal, inhaled or ophthalmic corticosteroids for acute or chronic conditions (e.g., allergic conjunctivitis, asthma/chronic obstructive pulmonary disease maintenance) is acceptable to the extent that, in the opinion of the Investigator, does not compromise safety of patient or integrity of data. 13. Use of oral terbinafine or itraconazole within 2 months before Visit 1. 14. Use of immunosuppressive medication or radiation therapy within 3 months before Visit 1. 15. Receipt of any drug as part of a research study within 30 days before Visit 1. 16. Previous participation in this study. 17. Employee of the Investigator or research center or their immediate family members. 18. Inability to understand the requirements of the study and the relative information or are unable or unwilling to comply with the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Equivalence: Per-Protocol Population) | Two weeks after the end of treatment (Day 56 ± 4) (Equivalence) | Equivalence: Per-Protocol Population Therapeutic Cure: To be considered a Therapeutic Cure, the patient must have both Clinical and Mycological Cure of tinea pedis. Therapeutic Failure: A patient will be considered a Therapeutic Failure if: 1. the patient is a Clinical or Mycological Failure 2. the patient was considered to have an insufficient therapeutic response 3. the patient used topical drug therapy for irritation or pruritus on the feet after the treatment phase of the study |
| Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | Two weeks after the end of treatment (Day 56 ± 4) (Superiority) | Superiority: modified Intent-to-Treat Population Therapeutic Cure: To be considered a Therapeutic Cure, the patient must have both Clinical and Mycological Cure of tinea pedis. Therapeutic Failure: A patient will be considered a Therapeutic Failure if: 1. the patient is a Clinical or Mycological Failure 2. the patient was considered to have an insufficient therapeutic response 3. the patient used topical drug therapy for irritation or pruritus on the feet after the treatment phase of the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Equivalence: Per-Protocol Population) | Two weeks after the end of treatment (Day 56 ± 4) (Equivalence) | Clinical Cure: To be considered a clinical cure the patient's total severity score must be ≤ 2 with no individual severity score \> 1. Clinical Failure: A patient will be considered a Clinical Failure if the patient's total severity score is \> 2 or any individual score is \> 1. Local Signs and Symptoms The most severely affected area will be identified as the target lesion at the baseline visit and will be used for the assessments at Day 42 and Day 56 visits. The Clinical Signs and Symptoms of tinea pedis will be rated by the Investigator as none, mild, moderate or severe using the following standardized rating scale. 0 = None (complete absence of any sign or symptom) 1. = Mild (Slight) 2. = Moderate (Definitely Present) 3. = Severe (Marked, Intense) The following signs and symptoms will be rated at each visit: * Signs: Fissuring/cracking, erythema, maceration, and scaling * Symptoms: Pruritus and burning/stinging |
| Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Equivalence: Per-Protocol Population) | Two weeks after the end of treatment (Day 56 ± 4) (Equivalence) | Mycological Cure: To be considered a mycological cure the patient must have a negative Potassium hydroxide (KOH) test and a negative fungal culture. Mycological Failure: A patient will be considered a Mycological Failure if the patient's KOH test is positive or the patient's fungal culture is positive. |
| Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | Two weeks after the end of treatment (Day 56 ± 4) (Superiority) | Clinical Cure: To be considered a clinical cure the patient's total severity score must be ≤ 2 with no individual severity score \> 1. Clinical Failure: A patient will be considered a Clinical Failure if the patient's total severity score is \> 2 or any individual score is \> 1. Local Signs and Symptoms The most severely affected area will be identified as the target lesion at the baseline visit and will be used for the assessments at Day 42 and Day 56 visits. The Clinical Signs and Symptoms of tinea pedis will be rated by the Investigator as none, mild, moderate or severe using the following standardized rating scale. 0 = None (complete absence of any sign or symptom) 1. = Mild (Slight) 2. = Moderate (Definitely Present) 3. = Severe (Marked, Intense) The following signs and symptoms will be rated at each visit: * Signs: Fissuring/cracking, erythema, maceration, and scaling * Symptoms: Pruritus and burning/stinging |
| Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | Two weeks after the end of treatment (Day 56 ± 4) (Superiority) | Mycological Cure: To be considered a mycological cure the patient must have a negative Potassium hydroxide (KOH) test and a negative fungal culture. Mycological Failure: A patient will be considered a Mycological Failure if the patient's KOH test is positive or the patient's fungal culture is positive. |
Countries
Belize, Saint Lucia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test: Ketoconazole Cream 2% Test: Ketoconazole Cream 2% (Encube Ethicals Pvt Ltd)
Ketoconazole Cream 2%: Patients will be instructed to apply sufficient study product to cover affected and immediate surrounding areas once daily for 42 ± 4 days. Each patient is expected to receive 42 ± 4 doses. | 314 |
| Reference: Ketoconazole Cream 2% Ketoconazole Cream 2% (G&W Laboratories Inc.; Registrant: Teva Pharmaceuticals USA Inc.)
Ketoconazole Cream 2% (G&W Laboratories Inc.): Patients will be instructed to apply sufficient study product to cover affected and immediate surrounding areas once daily for 42 ± 4 days. Each patient is expected to receive 42 ± 4 doses. | 319 |
| Placebo: Cream (Test Vehicle) Placebo Cream (Test vehicle) (Encube Ethicals Pvt Ltd)
Placebo: Patients will be instructed to apply sufficient study product to cover affected and immediate surrounding areas once daily for 42 ± 4 days. Each patient is expected to receive 42 ± 4 doses. | 156 |
| Total | 789 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 18 | 15 | 8 |
| Overall Study | Negative Baseline Culture Result | 118 | 112 | 57 |
| Overall Study | Non-Compliance with Study Drug | 0 | 0 | 1 |
| Overall Study | Participation in another study | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 4 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 1 |
Baseline characteristics
| Characteristic | Test: Ketoconazole Cream 2% | Reference: Ketoconazole Cream 2% | Placebo: Cream (Test Vehicle) | Total |
|---|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 13.6 | 46.7 years STANDARD_DEVIATION 13.9 | 44.8 years STANDARD_DEVIATION 14.4 | 45.9 years STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 154 Participants | 153 Participants | 75 Participants | 382 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 160 Participants | 166 Participants | 81 Participants | 407 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 147 Participants | 153 Participants | 74 Participants | 374 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 166 Participants | 163 Participants | 80 Participants | 409 Participants |
| Sex: Female, Male Female | 131 Participants | 114 Participants | 64 Participants | 309 Participants |
| Sex: Female, Male Male | 183 Participants | 205 Participants | 92 Participants | 480 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 314 | 0 / 319 | 0 / 156 |
| other Total, other adverse events | 12 / 314 | 15 / 319 | 6 / 156 |
| serious Total, serious adverse events | 0 / 314 | 0 / 319 | 0 / 156 |
Outcome results
Primary
Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Equivalence: Per-Protocol Population)
Equivalence: Per-Protocol Population Therapeutic Cure: To be considered a Therapeutic Cure, the patient must have both Clinical and Mycological Cure of tinea pedis. Therapeutic Failure: A patient will be considered a Therapeutic Failure if: 1. the patient is a Clinical or Mycological Failure 2. the patient was considered to have an insufficient therapeutic response 3. the patient used topical drug therapy for irritation or pruritus on the feet after the treatment phase of the study
Time frame: Two weeks after the end of treatment (Day 56 ± 4) (Equivalence)
Population: The Per-Protocol population was used for this analysis to determine equivalence between the Test and Reference groups only. To determine equivalence, only the test and reference treatment arms are analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test: Ketoconazole Cream 2% | Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Equivalence: Per-Protocol Population) | 89 Participants |
| Reference: Ketoconazole Cream 2% | Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Equivalence: Per-Protocol Population) | 90 Participants |
Primary
Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population)
Superiority: modified Intent-to-Treat Population Therapeutic Cure: To be considered a Therapeutic Cure, the patient must have both Clinical and Mycological Cure of tinea pedis. Therapeutic Failure: A patient will be considered a Therapeutic Failure if: 1. the patient is a Clinical or Mycological Failure 2. the patient was considered to have an insufficient therapeutic response 3. the patient used topical drug therapy for irritation or pruritus on the feet after the treatment phase of the study
Time frame: Two weeks after the end of treatment (Day 56 ± 4) (Superiority)
Population: The MITT Population was used for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test: Ketoconazole Cream 2% | Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | 92 Participants |
| Reference: Ketoconazole Cream 2% | Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | 94 Participants |
| Placebo: Cream (Test Vehicle) | Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | 26 Participants |
Secondary
Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Equivalence: Per-Protocol Population)
Clinical Cure: To be considered a clinical cure the patient's total severity score must be ≤ 2 with no individual severity score \> 1. Clinical Failure: A patient will be considered a Clinical Failure if the patient's total severity score is \> 2 or any individual score is \> 1. Local Signs and Symptoms The most severely affected area will be identified as the target lesion at the baseline visit and will be used for the assessments at Day 42 and Day 56 visits. The Clinical Signs and Symptoms of tinea pedis will be rated by the Investigator as none, mild, moderate or severe using the following standardized rating scale. 0 = None (complete absence of any sign or symptom) 1. = Mild (Slight) 2. = Moderate (Definitely Present) 3. = Severe (Marked, Intense) The following signs and symptoms will be rated at each visit: * Signs: Fissuring/cracking, erythema, maceration, and scaling * Symptoms: Pruritus and burning/stinging
Time frame: Two weeks after the end of treatment (Day 56 ± 4) (Equivalence)
Population: The Per-Protocol population was used for this analysis to determine equivalence between the Test and Reference groups only. To determine equivalence, only the test and reference treatment arms are analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test: Ketoconazole Cream 2% | Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Equivalence: Per-Protocol Population) | 97 Participants |
| Reference: Ketoconazole Cream 2% | Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Equivalence: Per-Protocol Population) | 110 Participants |
Secondary
Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population)
Clinical Cure: To be considered a clinical cure the patient's total severity score must be ≤ 2 with no individual severity score \> 1. Clinical Failure: A patient will be considered a Clinical Failure if the patient's total severity score is \> 2 or any individual score is \> 1. Local Signs and Symptoms The most severely affected area will be identified as the target lesion at the baseline visit and will be used for the assessments at Day 42 and Day 56 visits. The Clinical Signs and Symptoms of tinea pedis will be rated by the Investigator as none, mild, moderate or severe using the following standardized rating scale. 0 = None (complete absence of any sign or symptom) 1. = Mild (Slight) 2. = Moderate (Definitely Present) 3. = Severe (Marked, Intense) The following signs and symptoms will be rated at each visit: * Signs: Fissuring/cracking, erythema, maceration, and scaling * Symptoms: Pruritus and burning/stinging
Time frame: Two weeks after the end of treatment (Day 56 ± 4) (Superiority)
Population: The MITT population was used for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test: Ketoconazole Cream 2% | Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | 100 Participants |
| Reference: Ketoconazole Cream 2% | Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | 116 Participants |
| Placebo: Cream (Test Vehicle) | Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | 35 Participants |
Secondary
Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Equivalence: Per-Protocol Population)
Mycological Cure: To be considered a mycological cure the patient must have a negative Potassium hydroxide (KOH) test and a negative fungal culture. Mycological Failure: A patient will be considered a Mycological Failure if the patient's KOH test is positive or the patient's fungal culture is positive.
Time frame: Two weeks after the end of treatment (Day 56 ± 4) (Equivalence)
Population: The PP population was used for this analysis to determine equivalence between the Test and Reference groups only. One patient had an inconclusive result for the fungal culture at Visit 3 and was excluded from the analysis of the secondary endpoint for the mycological cure. Patient was a clinical failure and was included in the primary analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test: Ketoconazole Cream 2% | Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Equivalence: Per-Protocol Population) | 127 Participants |
| Reference: Ketoconazole Cream 2% | Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Equivalence: Per-Protocol Population) | 118 Participants |
Secondary
Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population)
Mycological Cure: To be considered a mycological cure the patient must have a negative Potassium hydroxide (KOH) test and a negative fungal culture. Mycological Failure: A patient will be considered a Mycological Failure if the patient's KOH test is positive or the patient's fungal culture is positive.
Time frame: Two weeks after the end of treatment (Day 56 ± 4) (Superiority)
Population: The MITT population was used for the analysis. One patient had an inconclusive result for the fungal culture at Visit 3 and was excluded from the analysis of the secondary endpoint for the mycological cure. Patient was a clinical failure and was included in the primary analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test: Ketoconazole Cream 2% | Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | 132 Participants |
| Reference: Ketoconazole Cream 2% | Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | 122 Participants |
| Placebo: Cream (Test Vehicle) | Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population) | 39 Participants |