Multiple-Site Study to Evaluate the Therapeutic Equivalence of Permethrin Cream, 5% in the Treatment of Scabies

• Sponsor: Encube Ethicals Pvt. Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03178942
• Collaborator: Novum Pharmaceutical Research Services (Industry)
• Enrollment: 254
• Locations: 15
• Arms: 2
• Actual Duration (Months): 5.4
• Patients Per Site: 16.9
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

Study to Evaluate the Therapeutic Equivalence of Permethrin Cream 5%in the Treatment of Scabies.

Condition or Disease	Intervention/Treatment	Phase
Scabies	Drug: Permethrin Cream, 5%; Drug: Elimite™ Cream (permethrin) 5%	Phase 3

Detailed Description

A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic Equivalence of Permethrin Cream 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) in the Treatment of Scabies.

The objectives of this study are to:

1. Evaluate the therapeutic equivalence of the Test formulation, Permethrin Cream, 5% (Encube Ethicals) to the marketed product, Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) in patients with scabies.

2. Compare the safety of Test and Reference treatments in patients with scabies.

Study Design

• Study Type: Interventional
• Actual Enrollment: 254 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be assigned to the test or reference permethrin to treat scabies.Patients will be assigned to the test or reference permethrin to treat scabies.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The study product will be randomized, packaged and blinded so that the packaging for both treatments look identical.
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (Permethrin) 5% (Prestium Pharma, Inc.) in the Treatment of Scabies
• Actual Study Start Date: Jun 1, 2017
• Actual Primary Completion Date: Nov 11, 2017
• Actual Study Completion Date: Nov 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Reference: Elimite™ Cream Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.)	Drug: Elimite™ Cream (permethrin) 5%; Permethrin Cream 5%; Other Names: Elimite™ Cream
Experimental: Test: Permethrin Cream, 5% Test: Permethrin Cream, 5% (Encube Ethicals)	Drug: Permethrin Cream, 5%; Permethrin Cream 5%

Outcome Measures

Primary Outcome Measures

1. Number of Patients in Each Treatment Group With Therapeutic Cure (Parasitological Cure Plus Clinical Cure) of Scabies [Day 28 ± 4]

   Parasitological cure is defined as failure to demonstrate microscopically the presence of scabies infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter present). Clinical cure is defined as visual evidence of absence of new lesions and healing of original lesions, regardless the presence of post-scabietic nodules (i.e., post-scabietic nodules need not be considered as new lesions or persistence of old lesions).

Other Outcome Measures

1. Number of Patients With a Therapeutic Cure That Completed Visit 2 Within 14 ± 2 Days and Visit 3 Within 28 ± 4 Days. [Visit 2 Within 14 ± 2 Days and Visit 3 Within 28 ± 4 Days]

   Parasitological cure is defined as failure to demonstrate microscopically the presence of scabies infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter present). Clinical cure is defined as visual evidence of absence of new lesions and healing of original lesions, regardless the presence of post-scabietic nodules (i.e., post-scabietic nodules need not be considered as new lesions or persistence of old lesions).

2. Number of Patients With a Therapeutic Cure That Completed Visit 2 Within 14 ± 2 Days and Visit 3 Between Day 26 and Day 32, Inclusive. [Visit 2 within 14 ± 2 days and Visit 3 between Day 26 and Day 32, inclusive.]

   Parasitological cure is defined as failure to demonstrate microscopically the presence of scabies infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter present). Clinical cure is defined as visual evidence of absence of new lesions and healing of original lesions, regardless the presence of post-scabietic nodules (i.e., post-scabietic nodules need not be considered as new lesions or persistence of old lesions).

3. Number of Patients With a Therapeutic Cure That Completed Visit 2 Within 14 ± 2 Days and Visit 3 Within 28 ± 2 Days. [Visit 2 Within 14 ± 2 Days and Visit 3 Within 28 ± 2 Days]

   Parasitological cure is defined as failure to demonstrate microscopically the presence of scabies infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter present). Clinical cure is defined as visual evidence of absence of new lesions and healing of original lesions, regardless the presence of post-scabietic nodules (i.e., post-scabietic nodules need not be considered as new lesions or persistence of old lesions).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or non-pregnant, non-lactating female, 2 years of age or older.

2. If female and of childbearing potential, prepared to abstain from sexual intercourse or use a reliable method of contraception during the study (e.g., double barrier methods, intrauterine device (IUD), oral, transdermal or injected hormonal contraceptives). Female patients using hormonal contraceptives should have been on the same product/dosing regimen for at least 28 days before baseline and should not change this regimen during the study.

3. Signed informed consent that meets all criteria of current FDA and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) regulations. For patients who are considered minors in the state the study is being conducted (< 18 years in most states) the parent or legal guardian should sign the consent form and the child will be required to sign a patient "assent" form, as appropriate. Patients 11-17 years of age will read and sign an Independent Review Board (IRB)-approved assent form and patients 6-10 years of age will provide verbal assent. Patients 2-5 years of age will be exempt from providing assent based on the child's comprehension and cognitive skills.

4. Clinical diagnosis of active scabies by presence of a burrow and/or typical scabietic lesions at the classic sites of infestation.

5. Parasitological confirmation of clinical diagnosis with demonstration under light microscope of mites and/or their products (larvae, eggs or fecal material).

6. Symptom score of 2 or 3 on a 4-point rating scale of 0-3 for nocturnal itching/pruritus.

7. Ability to apply or have study product applied as directed. If patient is a child, then parent/guardian will apply study product to him/her.

Exclusion Criteria:

1. Patients who are pregnant, lactating, or planning to become pregnant during the study.

2. Any systemic or dermatologic disorder that, in the opinion of the Investigator, will interfere with the study results or increase the risk of adverse events (AEs).

3. Known hypersensitivity to permethrin cream or any of its components.

4. Use of any systemic or topical acaricide or ectoparasiticide within one month before Screening.

5. Patient has signs of a systemic infection or is receiving systemic therapy for an infectious disease.

6. Patients with severe cutaneous bacterial or fungal infections requiring therapy (including systemic and topical antibiotics) or coexisting dermatological disorder that could interfere with the diagnosis and subsequent monitoring of scabies) or heavily crusted with lesions consistent with Norwegian scabies.

7. Patients with an underlying immunodeficient state (including prolonged treatment with corticosteroids), immunosuppressive disorders requiring therapy, severe systemic disease and history of HIV infection.

8. Any condition, medical, psychological, or social, that, in the Investigator's opinion, would interfere with participation in the study.

9. Family members of employees of the clinic or Investigator.

10. Patients who, in the opinion of the Investigator, would be non-compliant with the requirements of the study protocol.

11. Patients whose close personal contacts will not or are not willing to comply with standard of care for Scabies management.

12. Receipt of any drug as part of a research study within 30 days before Screening.

13. History of seizures.

14. Use of systemic corticosteroids within two weeks before Screening.

15. Use of topical corticosteroids within one week before Screening.

16. Previous participation in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Applied Research Center of Arkansas	Little Rock	Arkansas	United States	72212
2	St. Josephs Clinical Research	Anaheim	California	United States	92804
3	Long Beach Clinical Trials	Long Beach	California	United States	90806
4	Havana Research Institute	Pasadena	California	United States	91105
5	Integrity Clinical Research Center, Inc.	Hialeah	Florida	United States	33015
6	The Chappel Group Research	Kissimmee	Florida	United States	34744
7	Lenus Research & Medical Group, LLC	Sweetwater	Florida	United States	33172
8	DermDox Cetners for Dermatology	Hazleton	Pennsylvania	United States	18201
9	West Houston Clinical Research Services	Houston	Texas	United States	77055
10	Sun Research Instiute	San Antonio	Texas	United States	78215
11	Clinica Dermatologica/APF Research International	San Salvador		El Salvador	O1101
12	Clinica Dermatologica Y Cirugia de Piel/APF Research International	San Salvador		El Salvador	O1501
13	Clinica de la Doctora Laura Vargas	San Salvador		El Salvador
14	APF Research International	Aguas Buenas		Puerto Rico	OO703
15	APF Research International	Loiza		Puerto Rico	OO772

Sponsors and Collaborators

• Encube Ethicals Pvt. Ltd.
• Novum Pharmaceutical Research Services

Investigators

• Study Director: Pratik Kamani, Encube Ethicals Pvt. Ltd.

Study Documents (Full-Text)

• Study Protocol - Nov 3, 2017
• Statistical Analysis Plan - Nov 2, 2017

More Information

Publications

None provided.

• Responsible Party: Encube Ethicals Pvt. Ltd.
• ClinicalTrials.gov Identifier: NCT03178942
• Other Study ID Numbers: 71675502
• First Posted: Jun 7, 2017
• Last Update Posted: Mar 26, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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.: No
• Additional relevant MeSH terms: Scabies; Permethrin

Study Results

Participant Flow

Recruitment Details	Two hundred fifty-four (254) patients were randomized to study products. Thirteen (13) sites randomized patients into the study.The first patient was enrolled on 06/14/2017 and the last patient completed was on 10/30/2017. The time from first patient enrolled until last patient completed was approximately four months.
Pre-assignment Detail	All eligible patients were randomized at visit 1 and received the study product with instructions for dosing at home.

Arm/Group Title	Reference: Elimite™ Cream	Test: Permethrin Cream, 5%
Arm/Group Description	Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) Elimite™ Cream (permethrin) 5%: Permethrin Cream 5%	Test: Permethrin Cream, 5% (Encube Ethicals) Permethrin Cream, 5%: Permethrin Cream 5%
Period Title: Overall Study
STARTED	129	125
COMPLETED	126	123
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Reference: Elimite™ Cream	Test: Permethrin Cream, 5%	Total
Arm/Group Description	Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) Elimite™ Cream (permethrin) 5%: Permethrin Cream 5%	Test: Permethrin Cream, 5% (Encube Ethicals) Permethrin Cream, 5%: Permethrin Cream 5%	Total of all reporting groups
Overall Participants	129	125	254
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.7 (21.2)	37.7 (22.4)	39.2 (21.8)
Sex: Female, Male (Count of Participants)
Female	72 55.8%	73 58.4%	145 57.1%
Male	57 44.2%	52 41.6%	109 42.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	96 74.4%	97 77.6%	193 76%
Not Hispanic or Latino	33 25.6%	28 22.4%	61 24%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.8%	0 0%	1 0.4%
Asian	3 2.3%	2 1.6%	5 2%
Native Hawaiian or Other Pacific Islander	2 1.6%	0 0%	2 0.8%
Black or African American	14 10.9%	15 12%	29 11.4%
White	109 84.5%	108 86.4%	217 85.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Puerto Rico	6 4.7%	6 4.8%	12 4.7%
El Salvador	63 48.8%	62 49.6%	125 49.2%
United States	60 46.5%	57 45.6%	117 46.1%
Baseline Severity Score of Nocturnal Itching Pretreatment (Count of Participants)
None	0 0%	0 0%	0 0%
Mild	0 0%	0 0%	0 0%
Moderate	112 86.8%	110 88%	222 87.4%
Severe	17 13.2%	15 12%	32 12.6%
Baseline Severity of Lesion Count Infestation Pretreatment (Count of Participants)
Mild	47 36.4%	45 36%	92 36.2%
Moderate	68 52.7%	57 45.6%	125 49.2%
Severe	14 10.9%	23 18.4%	37 14.6%

Outcome Measures

1. Primary Outcome

Title	Number of Patients in Each Treatment Group With Therapeutic Cure (Parasitological Cure Plus Clinical Cure) of Scabies
Description	Parasitological cure is defined as failure to demonstrate microscopically the presence of scabies infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter present). Clinical cure is defined as visual evidence of absence of new lesions and healing of original lesions, regardless the presence of post-scabietic nodules (i.e., post-scabietic nodules need not be considered as new lesions or persistence of old lesions).
Time Frame	Day 28 ± 4

Outcome Measure Data

Analysis Population Description

The Per Protocol (PP) population was used for the analysis.

Arm/Group Title	Reference: Elimite™ Cream	Test: Permethrin Cream, 5%
Arm/Group Description	Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) Elimite™ Cream (permethrin) 5%: Permethrin Cream 5%	Test: Permethrin Cream, 5% (Encube Ethicals) Permethrin Cream, 5%: Permethrin Cream 5%
Measure Participants	119	117
Count of Participants [Participants]	83 64.3%	86 68.8%

2. Other Pre-specified Outcome

Title	Number of Patients With a Therapeutic Cure That Completed Visit 2 Within 14 ± 2 Days and Visit 3 Within 28 ± 4 Days.
Description	Parasitological cure is defined as failure to demonstrate microscopically the presence of scabies infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter present). Clinical cure is defined as visual evidence of absence of new lesions and healing of original lesions, regardless the presence of post-scabietic nodules (i.e., post-scabietic nodules need not be considered as new lesions or persistence of old lesions).
Time Frame	Visit 2 Within 14 ± 2 Days and Visit 3 Within 28 ± 4 Days

Outcome Measure Data

Analysis Population Description

Patients who completed Visit 2 within 14 ± 2 days and Visit 3 within 28 ± 4 days

Arm/Group Title	Reference: Elimite™ Cream	Test: Permethrin Cream, 5%
Arm/Group Description	Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) Elimite™ Cream (permethrin) 5%: Permethrin Cream 5%	Test: Permethrin Cream, 5% (Encube Ethicals) Permethrin Cream, 5%: Permethrin Cream 5%
Measure Participants	110	110
Count of Participants [Participants]	77 59.7%	81 64.8%

3. Other Pre-specified Outcome

Title	Number of Patients With a Therapeutic Cure That Completed Visit 2 Within 14 ± 2 Days and Visit 3 Between Day 26 and Day 32, Inclusive.
Description	Parasitological cure is defined as failure to demonstrate microscopically the presence of scabies infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter present). Clinical cure is defined as visual evidence of absence of new lesions and healing of original lesions, regardless the presence of post-scabietic nodules (i.e., post-scabietic nodules need not be considered as new lesions or persistence of old lesions).
Time Frame	Visit 2 within 14 ± 2 days and Visit 3 between Day 26 and Day 32, inclusive.

Outcome Measure Data

Analysis Population Description

Number of patients with a Therapeutic Cure that completed Visit 2 within 14 ± 2 days and Visit 3 between Day 26 and Day 32, inclusive.

Arm/Group Title	Reference: Elimite™ Cream	Test: Permethrin Cream, 5%
Arm/Group Description	Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) Elimite™ Cream (permethrin) 5%: Permethrin Cream 5%	Test: Permethrin Cream, 5% (Encube Ethicals) Permethrin Cream, 5%: Permethrin Cream 5%
Measure Participants	101	102
Count of Participants [Participants]	68 52.7%	75 60%

4. Other Pre-specified Outcome

Title	Number of Patients With a Therapeutic Cure That Completed Visit 2 Within 14 ± 2 Days and Visit 3 Within 28 ± 2 Days.
Description	Parasitological cure is defined as failure to demonstrate microscopically the presence of scabies infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter present). Clinical cure is defined as visual evidence of absence of new lesions and healing of original lesions, regardless the presence of post-scabietic nodules (i.e., post-scabietic nodules need not be considered as new lesions or persistence of old lesions).
Time Frame	Visit 2 Within 14 ± 2 Days and Visit 3 Within 28 ± 2 Days

Outcome Measure Data

Analysis Population Description

Patients who completed Visit 2 within 14 ± 2 days and Visit 3 within 28 ± 2 days

Arm/Group Title	Reference: Elimite™ Cream	Test: Permethrin Cream, 5%
Arm/Group Description	Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) Elimite™ Cream (permethrin) 5%: Permethrin Cream 5%	Test: Permethrin Cream, 5% (Encube Ethicals) Permethrin Cream, 5%: Permethrin Cream 5%
Measure Participants	95	100
Count of Participants [Participants]	65 50.4%	73 58.4%

Adverse Events

Time Frame	4.5 months
Arm/Group Title	Reference: Elimite™ Cream		Test: Permethrin Cream, 5%
Arm/Group Description	Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) Elimite™ Cream (permethrin) 5%: Permethrin Cream 5%		Test: Permethrin Cream, 5% (Encube Ethicals) Permethrin Cream, 5%: Permethrin Cream 5%
All Cause Mortality
	Reference: Elimite™ Cream		Test: Permethrin Cream, 5%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/129 (0%)		0/125 (0%)
Serious Adverse Events
	Reference: Elimite™ Cream		Test: Permethrin Cream, 5%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/129 (0%)		1/125 (0.8%)
Infections and infestations
Left Foot Cellulitus	0/129 (0%)	0	1/125 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Reference: Elimite™ Cream		Test: Permethrin Cream, 5%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/129 (5.4%)		7/125 (5.6%)
Gastrointestinal disorders
Enterocolitis/Acute Colitis	0/129 (0%)	0	1/125 (0.8%)	1
Abdominal Pain/Upper Epigastralgia	1/129 (0.8%)	1	0/125 (0%)	0
General disorders
Application Site Hypoaesthesia	1/129 (0.8%)	1	0/125 (0%)	0
Application Site Paraesthesia	1/129 (0.8%)	1	0/125 (0%)	0
Application Site Rash/Rash	1/129 (0.8%)	1	0/125 (0%)	0
Infections and infestations
Viral Upper Respiratory Tract Infection/Common Cold	0/129 (0%)	0	1/125 (0.8%)	1
Pharyngitis/Pharyngitis	1/129 (0.8%)	1	0/125 (0%)	0
Musculoskeletal and connective tissue disorders
Pain In Extremity/Leg Pain	0/129 (0%)	0	1/125 (0.8%)	1
Bone Pain/Bone Ache	0/129 (0%)	0	1/125 (0.8%)	1
Nervous system disorders
Headache	2/129 (1.6%)	2	2/125 (1.6%)	2
Skin and subcutaneous tissue disorders
Erythema In Helix Skin Of The Right Ear	0/129 (0%)	0	1/125 (0.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.