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Clinical Study to Evaluate the Therapeutic Equivalence of Ketoconazole Cream 2% in the Treatment of Tinea Pedis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03824912
Recruitment Status : Completed
First Posted : January 31, 2019
Results First Posted : June 13, 2019
Last Update Posted : June 27, 2019
Sponsor:
Collaborators:
Novum Pharmaceutical Research Services
ACM Global Laboratories
Information provided by (Responsible Party):
Encube Ethicals Pvt. Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Tinea Pedis
Interventions Drug: Ketoconazole Cream 2%
Drug: Ketoconazole Cream 2% (G&W Laboratories Inc.)
Drug: Placebo
Enrollment 831
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2% Placebo: Cream (Test Vehicle)
Hide Arm/Group Description

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.

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.

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.

Period Title: Overall Study
Started 332 335 164
Completed 192 201 96
Not Completed 140 134 68
Reason Not Completed
Lost to Follow-up             18             15             8
Negative Baseline Culture Result             118             112             57
Non-Compliance with Study Drug             0             0             1
Protocol Violation             1             4             1
Withdrawal by Subject             3             2             1
Participation in another study             0             1             0
Arm/Group Title Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2% Placebo: Cream (Test Vehicle) Total
Hide Arm/Group Description

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.

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 314 319 156 789
Hide Baseline Analysis Population Description
The Safety population was used for the baseline analysis population. The Safety population included all randomized patients who used at least one dose of product.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 314 participants 319 participants 156 participants 789 participants
45.6  (13.6) 46.7  (13.9) 44.8  (14.4) 45.9  (13.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 319 participants 156 participants 789 participants
Female
131
  41.7%
114
  35.7%
64
  41.0%
309
  39.2%
Male
183
  58.3%
205
  64.3%
92
  59.0%
480
  60.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 319 participants 156 participants 789 participants
Hispanic or Latino
154
  49.0%
153
  48.0%
75
  48.1%
382
  48.4%
Not Hispanic or Latino
160
  51.0%
166
  52.0%
81
  51.9%
407
  51.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 319 participants 156 participants 789 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
1
   0.6%
1
   0.1%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
147
  46.8%
153
  48.0%
74
  47.4%
374
  47.4%
White
166
  52.9%
163
  51.1%
80
  51.3%
409
  51.8%
More than one race
1
   0.3%
3
   0.9%
1
   0.6%
5
   0.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Equivalence: Per-Protocol Population)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2%
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 184 191
Measure Type: Count of Participants
Unit of Measure: Participants
89
  48.4%
90
  47.1%
2.Primary Outcome
Title Primary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Therapeutic Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
The MITT Population was used for analysis.
Arm/Group Title Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2% Placebo: Cream (Test Vehicle)
Hide Arm/Group Description:

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.

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.

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.

Overall Number of Participants Analyzed 195 199 97
Measure Type: Count of Participants
Unit of Measure: Participants
92
  47.2%
94
  47.2%
26
  26.8%
3.Secondary Outcome
Title Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Equivalence: Per-Protocol Population)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2%
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 184 191
Measure Type: Count of Participants
Unit of Measure: Participants
97
  52.7%
110
  57.6%
4.Secondary Outcome
Title Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Equivalence: Per-Protocol Population)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2%
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 184 190
Measure Type: Count of Participants
Unit of Measure: Participants
127
  69.0%
118
  62.1%
5.Secondary Outcome
Title Secondary Efficacy Endpoint: The Number of Patients in Each Treatment Group With a Clinical Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
The MITT population was used for analysis.
Arm/Group Title Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2% Placebo: Cream (Test Vehicle)
Hide Arm/Group Description:

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.

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.

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.

Overall Number of Participants Analyzed 195 199 97
Measure Type: Count of Participants
Unit of Measure: Participants
100
  51.3%
116
  58.3%
35
  36.1%
6.Secondary Outcome
Title Secondary Efficacy Endpoint:The Number of Patients in Each Treatment Group With a Mycological Cure of Tinea Pedis (Superiority: Modified Intent-to-Treat Population)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2% Placebo: Cream (Test Vehicle)
Hide Arm/Group Description:

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.

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.

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.

Overall Number of Participants Analyzed 195 198 97
Measure Type: Count of Participants
Unit of Measure: Participants
132
  67.7%
122
  61.6%
39
  40.2%
Time Frame 5 months
Adverse Event Reporting Description

The "Total Number of Participants at Risk" is not consistent with the numbers provided in any of the rows in the Participant Flow module, since the Overall Summary of Adverse Events is based on the Safety Population.

The Safety population will include all randomized patients who use at least one dose of product.

 
Arm/Group Title Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2% Placebo: Cream (Test Vehicle)
Hide Arm/Group Description

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.

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.

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.

All-Cause Mortality
Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2% Placebo: Cream (Test Vehicle)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/314 (0.00%)      0/319 (0.00%)      0/156 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2% Placebo: Cream (Test Vehicle)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/314 (0.00%)      0/319 (0.00%)      0/156 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Test: Ketoconazole Cream 2% Reference: Ketoconazole Cream 2% Placebo: Cream (Test Vehicle)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/314 (3.82%)      15/319 (4.70%)      6/156 (3.85%)    
Gastrointestinal disorders       
Diarrhoea * 1  1/314 (0.32%)  1 1/319 (0.31%)  1 0/156 (0.00%)  0
Dyspepsia * 1  0/314 (0.00%)  0 1/319 (0.31%)  1 0/156 (0.00%)  0
Gastritis * 1  0/314 (0.00%)  0 0/319 (0.00%)  0 1/156 (0.64%)  1
Toothache * 1  0/314 (0.00%)  0 0/319 (0.00%)  0 1/156 (0.64%)  1
Infections and infestations       
Nasopharyngitis * 1  4/314 (1.27%)  4 4/319 (1.25%)  4 1/156 (0.64%)  1
Upper respiratory tract infection * 1  1/314 (0.32%)  1 0/319 (0.00%)  0 0/156 (0.00%)  0
Injury, poisoning and procedural complications       
Arthropod bite * 1  0/314 (0.00%)  0 1/319 (0.31%)  1 0/156 (0.00%)  0
Contusion * 1  0/314 (0.00%)  0 1/319 (0.31%)  1 0/156 (0.00%)  0
Investigations       
Blood pressure increased * 1  1/314 (0.32%)  1 0/319 (0.00%)  0 1/156 (0.64%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  0/314 (0.00%)  0 0/319 (0.00%)  0 1/156 (0.64%)  1
Back pain * 1  1/314 (0.32%)  1 2/319 (0.63%)  2 0/156 (0.00%)  0
Joint swelling * 1  0/314 (0.00%)  0 0/319 (0.00%)  0 1/156 (0.64%)  1
Muscle spasms * 1  0/314 (0.00%)  0 2/319 (0.63%)  2 0/156 (0.00%)  0
Pain in extremity * 1  0/314 (0.00%)  0 2/319 (0.63%)  2 0/156 (0.00%)  0
Nervous system disorders       
Headache * 1  3/314 (0.96%)  3 5/319 (1.57%)  6 0/156 (0.00%)  0
Reproductive system and breast disorders       
Adnexa uteri pain * 1  0/314 (0.00%)  0 0/319 (0.00%)  0 1/156 (0.64%)  1
Dysmenorrhoea * 1  1/314 (0.32%)  1 0/319 (0.00%)  0 0/156 (0.00%)  0
Skin and subcutaneous tissue disorders       
Blister * 1  1/314 (0.32%)  1 0/319 (0.00%)  0 0/156 (0.00%)  0
1
Term from vocabulary, MedDRA 21.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In the Clinical Trials Agreements between the sites and the Contract Research Organization, sites are instructed that the Investigator shall not publish, or seek to publish, either in whole or in part any results of the Study without the written consent.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Lalatendu Panigrahi, Chief Scientific Officer
Organization: Encube Ethicals Pvt Ltd
Phone: +91-22-6264-7002
EMail: lalatendu.p@encubeethicals.com
Layout table for additonal information
Responsible Party: Encube Ethicals Pvt. Ltd.
ClinicalTrials.gov Identifier: NCT03824912     History of Changes
Other Study ID Numbers: 71875502
First Submitted: January 29, 2019
First Posted: January 31, 2019
Results First Submitted: April 11, 2019
Results First Posted: June 13, 2019
Last Update Posted: June 27, 2019