Therapeutic Equivalence and Safety of Two Econazole Nitrate Cream, 1% Products in Tinea Pedis

• Sponsor: Mylan Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03129321
• Collaborator: DPT Laboratories, Ltd. (Industry)
• Enrollment: 876
• Arms: 3
• Actual Duration (Months): 8.1

Study Details

Study Description

Brief Summary

To evaluate the therapeutic equivalence of the Test formulation, econazole nitrate cream, 1% to the Reference product, econazole nitrate cream, 1% in the treatment of tinea pedis.

To demonstrate the superiority of the Test and Reference (active) treatments over Placebo treatment in patients with tinea pedis.

To compare the safety of Test, Reference and Placebo treatments in patients with tinea pedis.

Condition or Disease	Intervention/Treatment	Phase
Tinea Pedis	Drug: Econazole Nitrate Cream, 1%; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 876 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clinical Study to Evaluate the Therapeutic Equivalence and Safety of Econazole Nitrate Cream, 1% (Renaissance Pharma, Inc.) to Econazole Nitrate Cream, 1% (Perrigo New York Inc.) in Tinea Pedis
• Actual Study Start Date: Mar 15, 2016
• Actual Primary Completion Date: Nov 17, 2016
• Actual Study Completion Date: Nov 17, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days	Drug: Econazole Nitrate Cream, 1%
Active Comparator: Reference Standard Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days	Drug: Econazole Nitrate Cream, 1%
Placebo Comparator: Placebo Placebo Cream, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients in Each Active Treatment Group Who Are Considered a Therapeutic Cure [Day 42]

   To be considered a Therapeutic Cure, the patient must have both Clinical Cure (patient's total severity score must be ≤ 2 with no individual severity score > 1) and Mycological Cure (patient must have a negative KOH test and a negative fungal culture) of tinea pedis

2. Proportion of Patients in Each Treatment Group Who Are Considered a Therapeutic Cure [Day 42]

   To be considered a Therapeutic Cure, the patient must have both Clinical Cure (patient's total severity score must be ≤ 2 with no individual severity score > 1) and Mycological Cure (patient must have a negative KOH test and a negative fungal culture) of tinea pedis

Secondary Outcome Measures

1. Proportion of Patients in Each Active Treatment Group Who Are Considered a Clinical Cure (Patient's Total Severity Score Must be ≤ 2 With no Individual Severity Score > 1) [Day 42]

   The following Clinical Signs and Symptoms of a target lesion with tinea pedis are individually rated for severity (none, mild, moderate, or severe): fissuring/cracking, erythema, maceration, scaling, pruritus, and burning/stinging

2. Proportion of Patients in Each Active Treatment Group Who Are Considered a Mycological Cure [Day 42]

   To be considered a mycological cure the patient must have a negative KOH test and a negative fungal culture for T. rubrum, T. mentagrophytes or E. floccosum

3. Proportion of Patients in Each Treatment Group Who Are Considered a Clinical Cure (Patient's Total Severity Score Must be ≤ 2 With no Individual Severity Score > 1) [Day 42]

   The following Clinical Signs and Symptoms of a target lesion with tinea pedis are individually rated for severity (none, mild, moderate, or severe): fissuring/cracking, erythema, maceration, scaling, pruritus, and burning/stinging

4. Proportion of Patients in Each Treatment Group Who Are Considered a Mycological Cure [Day 42]

   To be considered a mycological cure the patient must have a negative KOH test and a negative fungal culture for T. rubrum, T. mentagrophytes or E. floccosum

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Healthy male or non-pregnant, non-lactating female ≥ 18 years of age.

• 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).

• Provisionally confirmed at baseline by a positive potassium hydroxide (KOH) wet mount preparation

• Total score ≥ 4 for the clinical signs and symptoms of tinea pedis in the target area. In addition the target area must have a minimum score of at least 2 for erythema and a minimum score of at least 2 for either pruritus or scaling.

Exclusion Criteria:

• 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

• History of or current psoriasis, Lichen planus or contact dermatitis involving the feet within the previous 12 months.

• Past history of dermatophyte infections with a lack of response to antifungal therapy

• Confluent, diffuse moccasin-type tinea pedis of the entire plantar surface or onychomycosis involving ≥ 20% of the area of either great toenail and/or involving more than five toenails in total or other concurrent dermatophytoses (e.g., tinea cruris) and any other skin disease to an extent that, in the opinion of the investigator, might interfere with the evaluation of tinea pedis or study results

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Mylan Inc.
• DPT Laboratories, Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT03129321
• Other Study ID Numbers: 71532902
• First Posted: Apr 26, 2017
• Last Update Posted: Mar 7, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Tinea; Tinea Pedis; Econazole

Study Results

Participant Flow

Arm/Group Title	Test	Reference Standard	Placebo
Arm/Group Description	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Placebo Cream, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Placebo
Period Title: Overall Study
STARTED	351	350	175
COMPLETED	253	241	120
NOT COMPLETED	98	109	55

Baseline Characteristics

Arm/Group Title	Test	Reference Standard	Placebo	Total
Arm/Group Description	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Placebo Cream, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Placebo	Total of all reporting groups
Overall Participants	351	350	175	876
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (12.9)	47.1 (14.6)	46.1 (13.3)	47.0 (13.7)
Sex: Female, Male (Count of Participants)
Female	127 36.2%	114 32.6%	60 34.3%	301 34.4%
Male	224 63.8%	236 67.4%	115 65.7%	575 65.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	168 47.9%	165 47.1%	81 46.3%	414 47.3%
Not Hispanic or Latino	183 52.1%	185 52.9%	94 53.7%	462 52.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	191 54.4%	197 56.3%	93 53.1%	481 54.9%
Black/African American	149 42.5%	142 40.6%	74 42.3%	365 41.7%
Native Hawaiian or other Pacific Islander	1 0.3%	0 0%	0 0%	1 0.1%
Asian	3 0.9%	4 1.1%	2 1.1%	9 1%
American Indian or Alaska Native	0 0%	1 0.3%	1 0.6%	2 0.2%
Other	7 2%	6 1.7%	5 2.9%	18 2.1%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients in Each Active Treatment Group Who Are Considered a Therapeutic Cure
Description	To be considered a Therapeutic Cure, the patient must have both Clinical Cure (patient's total severity score must be ≤ 2 with no individual severity score > 1) and Mycological Cure (patient must have a negative KOH test and a negative fungal culture) of tinea pedis
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

Active Treatments of the Per Protocol Population

Arm/Group Title	Test	Reference Standard
Arm/Group Description	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%
Measure Participants	185	170
Count of Participants [Participants]	96 27.4%	81 23.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Reference Standard
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin: +/-20%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	4.24
	Confidence Interval	(2-Sided) 90%; -5.05 to 13.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Proportion of Patients in Each Treatment Group Who Are Considered a Therapeutic Cure
Description	To be considered a Therapeutic Cure, the patient must have both Clinical Cure (patient's total severity score must be ≤ 2 with no individual severity score > 1) and Mycological Cure (patient must have a negative KOH test and a negative fungal culture) of tinea pedis
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat. Patients who are missing mycological culture data at baseline are not included in the analysis. Patients who are missing mycological culture data at the test of cure visit are not included in the analysis unless they were a treatment failure.

Arm/Group Title	Test	Reference Standard	Placebo
Arm/Group Description	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Placebo Cream, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Placebo
Measure Participants	201	188	90
Count of Participants [Participants]	102 29.1%	88 25.1%	22 12.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Reference Standard, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	Proportion of Patients in Each Active Treatment Group Who Are Considered a Clinical Cure (Patient's Total Severity Score Must be ≤ 2 With no Individual Severity Score > 1)
Description	The following Clinical Signs and Symptoms of a target lesion with tinea pedis are individually rated for severity (none, mild, moderate, or severe): fissuring/cracking, erythema, maceration, scaling, pruritus, and burning/stinging
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

Active treatment groups of the Per Protocol population

Arm/Group Title	Test	Reference Standard
Arm/Group Description	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%
Measure Participants	185	170
Count of Participants [Participants]	113 32.2%	99 28.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Reference Standard
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin: +/-20%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	2.85
	Confidence Interval	(2-Sided) 90%; -6.29 to 11.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Proportion of Patients in Each Active Treatment Group Who Are Considered a Mycological Cure
Description	To be considered a mycological cure the patient must have a negative KOH test and a negative fungal culture for T. rubrum, T. mentagrophytes or E. floccosum
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

Active treatment groups of the Per Protocol population

Arm/Group Title	Test	Reference Standard
Arm/Group Description	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%
Measure Participants	185	170
Count of Participants [Participants]	136 38.7%	125 35.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Reference Standard
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin: +/-20%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 90%; -8.29 to 8.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Proportion of Patients in Each Treatment Group Who Are Considered a Clinical Cure (Patient's Total Severity Score Must be ≤ 2 With no Individual Severity Score > 1)
Description	The following Clinical Signs and Symptoms of a target lesion with tinea pedis are individually rated for severity (none, mild, moderate, or severe): fissuring/cracking, erythema, maceration, scaling, pruritus, and burning/stinging
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat

Arm/Group Title	Test	Reference Standard	Placebo
Arm/Group Description	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Placebo Cream, topical,
Measure Participants	214	198	95
Count of Participants [Participants]	131 37.3%	113 32.3%	40 22.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Reference Standard, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

6. Secondary Outcome

Title	Proportion of Patients in Each Treatment Group Who Are Considered a Mycological Cure
Description	To be considered a mycological cure the patient must have a negative KOH test and a negative fungal culture for T. rubrum, T. mentagrophytes or E. floccosum
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat. Patients who are missing mycological culture data at baseline are not included in the analysis. Patients who are missing mycological culture data at the test of cure visit are not included in the analysis unless they were a treatment failure.

Arm/Group Title	Test	Reference Standard	Placebo
Arm/Group Description	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%	Placebo Cream, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Placebo Cream
Measure Participants	201	188	90
Count of Participants [Participants]	147 41.9%	137 39.1%	37 21.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Reference Standard, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Arm/Group Title	Test		Reference Standard		Placebo
Arm/Group Description	Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%		Econazole Nitrate Cream, 1%, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Econazole Nitrate Cream, 1%		Placebo Cream, topical, sufficient amount to cover all affected areas on the feet once daily for 28 days Placebo
All Cause Mortality
	Test		Reference Standard		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Test		Reference Standard		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/351 (0%)		0/350 (0%)		0/175 (0%)
Other (Not Including Serious) Adverse Events
	Test		Reference Standard		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/351 (0%)		0/350 (0%)		0/175 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator shall not publish, or seek to publish, either in whole or in part any results of the study without the written consent of CRO.