To Compare Safety and Efficacy of Perrigo's Drug Product Compared to an FDA Approved Drug Product in the Treatment of Actinic Keratosis

• Sponsor: Padagis LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02385318
• Collaborator: (none)
• Enrollment: 519
• Arms: 3
• Duration (Months): 10

Study Details

Study Description

Brief Summary

The purpose of this study is to compare safety and efficacy of Perrigo's drug product compared to an FDA approved drug product in the treatment of actinic keratosis.

Condition or Disease	Intervention/Treatment	Phase
Actinic Keratosis	Drug: Ingenol Mebutate (Perrigo); Drug: Ingenol Mebutate (Reference); Drug: Placebo gel	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 519 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test Product Ingenol Mebutate	Drug: Ingenol Mebutate (Perrigo); Other Names: Perrigo product
Active Comparator: Reference product Ingenol Mebutate	Drug: Ingenol Mebutate (Reference); Other Names: Reference Listed Drug Product
Placebo Comparator: Placebo product Placebo gel	Drug: Placebo gel

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Clearance (Absence) of Actinic Keratosis Lesions as Determined by Visual Inspection of the Investigator [Day 57]

Eligibility Criteria

Criteria

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

Inclusion Criteria

1. Provide written informed consent/assent

2. Healthy male or non-pregnant females, >18 years old

3. Subjects must have clinical diagnosis of actinic keratosis

4. Subjects must be in general good health and free from any clinically significant disease that might interfere with the study evaluations in the opinion of the investigator

5. Subjects must be willing to refrain from using non-approved products on the targeted treatment area during the study period.

6. Subjects should be willing to refrain from using any type of bandage or dressing on the treatment area or apply the gel to open skin wounds, infections, or exfoliative dermatitis.

7. Subjects must be willing and able to comply with the requirements of the study for the duration of the study period.

8. Females of childbearing potential willing to use an acceptable form of birth control

Exclusion

1. Females who are pregnant, nursing, or planning a pregnancy within the study participation period

2. Subjects who are immunocompromised or HIV positive or who have any immune-system disorders including auto-immune disease

3. Subjects who have or had an active herpes infection within 14 days prior to the baseline visit

4. Subjects who have any evidence of carcinoma or any other cancer on the face and scalp

5. Presence of an incompletely healed wound within the treatment area or within 5cm of the treatment area

6. Presence of any skin condition in the treatment area that may be made worse by treatment with the study medication

7. Subjects who have used a tanning salon, tanning booth, sunbathing or have excessive prolonged exposure to the sun 7 days prior to Visit 1/Day 1 (baseline) or planned throughout the study

8. Subjects who plan to use artificial tanners within 5cm of the selected treatment area throughout the study

9. Use of NSAIDs within 7 days from Visit 1/Day 1 (Baseline) or initiation during the trial.

10. Subjects who had select cosmetic or therapeutic procedures within 2cm of the selected treatment area and within 14 days of Visit 1/Day 1 (baseline) or within 10cm of the selected treatment area planned anytime during the study.

11. Subjects who have had or are scheduling elective surgery within 1 month before or after the study period

12. Prior use within 30 days of Visit 1/ Day 1 (baseline) or planned use during the study of immunomodulators, immunosuppressive therapies, interferon, interferon inducers, systemic corticosteroids, and cytotoxic drugs

13. Subjects undergoing treatment or received treatment within 8 weeks of Visit 1/Day 1 (baseline) and within 2cm of the selected area or planned during anytime in the study of: 5-FU, imiquimod, diclofenac, photodynamic therapy used in combination with photosensitizing cream.

14. Subjects who used PUVA or UVB therapy on the face or scalp within 6 months prior to Visit 1/Day 1 (baseline) or are planning to receive PUVA therapy, UVB therapy, or nonprescription UV light sources anywhere on the body during the study.

15. Subjects who have taken systemic chemotherapy medications within the last 6 months prior to Visit 1/Day 1 (baseline) or planned use anytime during the study.

16. Subjects who have undergone resurfacing procedures within the last 6 months prior to Visit 1/Day 1 (baseline) or planned use anytime during the study.

17. Subjects who have been treated within 1 month or planning to receive treatment with systemic retinoids, hyaluronic acid, other medicated actinic keratosis therapy, or topical steroids anywhere on the head during the study.

18. Subject who have a history of hypersensitivity or allergy to any ingredient in the drug product.

19. Use of medicated make-up in the treatment area or significant change in the use of consumer products within 30 days of Visit 1/Day 1 (baseline) and planned use or change throughout the study.

20. Start or change of dose of hormonal treatment within the past 3 months (90 days) or planned start/change throughout the study.

21. Subject consumes excessive alcohol, abuses drugs, or has a condition that could compromise the subject's ability to comply with study requirements

22. Participation in any clinical study involving an investigational product, agent, or device in the 30 days prior to Visit 1/Day 1 (baseline) or throughout the study

23. Subjects who have been previously enrolled in this study

24. Employee of the research center or private practice

25. Subjects who in the opinion of the investigator are unlikely to be able to follow the restrictions of the protocol and complete the study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Padagis LLC

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 15, 2015
• Statistical Analysis Plan - Apr 15, 2015

More Information

Publications

None provided.

• Responsible Party: Padagis LLC
• ClinicalTrials.gov Identifier: NCT02385318
• Other Study ID Numbers: PRG-NY-14-019
• First Posted: Mar 11, 2015
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Additional relevant MeSH terms: Keratosis, Actinic; Keratosis

Study Results

Participant Flow

Arm/Group Title	Test Product	Reference Product	Placebo Product
Arm/Group Description	Ingenol Mebutate gel (Perrigo)	Ingenol Mebutate gel (Reference)	Placebo gel Placebo gel
Period Title: Overall Study
STARTED	204	210	105
COMPLETED	200	203	99
NOT COMPLETED	4	7	6

Baseline Characteristics

Arm/Group Title	Test Product	Reference Product	Placebo Product	Total
Arm/Group Description	Ingenol Mebutate Ingenol Mebutate (Perrigo)	Ingenol Mebutate Ingenol Mebutate (Reference)	Placebo gel Placebo gel	Total of all reporting groups
Overall Participants	204	210	105	519
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.6 (9.66)	67.9 (9.91)	68.4 (9.67)	67.9 (9.75)
Sex: Female, Male (Count of Participants)
Female	43 21.1%	54 25.7%	18 17.1%	115 22.2%
Male	161 78.9%	156 74.3%	87 82.9%	404 77.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 2.9%	2 1%	5 4.8%	13 2.5%
Not Hispanic or Latino	198 97.1%	208 99%	100 95.2%	506 97.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.5%	0 0%	1 0.2%
Asian	0 0%	1 0.5%	0 0%	1 0.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 1%	1 0.2%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	203 99.5%	207 98.6%	104 99%	514 99%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 0.5%	1 0.5%	0 0%	2 0.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Clearance (Absence) of Actinic Keratosis Lesions as Determined by Visual Inspection of the Investigator
Time Frame	Day 57

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Test Product	Reference Product	Placebo Product
Arm/Group Description	Ingenol Mebutate Ingenol Mebutate (Perrigo)	Ingenol Mebutate Ingenol Mebutate (Reference)	Placebo gel Placebo gel
Measure Participants	168	176	83
Count of Participants [Participants]	81 39.7%	76 36.2%	10 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Product, Reference Product
	Comments
	Type of Statistical Test	Equivalence
	Comments	85% power of success
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Equivalence ratio
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 90%; -4.38 to 14.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	57 days
Arm/Group Title	Test Product		Reference Product		Placebo Product
Arm/Group Description	Ingenol Mebutate Ingenol Mebutate (Perrigo)		Ingenol Mebutate Ingenol Mebutate (Reference)		Placebo gel Placebo gel
All Cause Mortality
	Test Product		Reference Product		Placebo Product
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/204 (0.5%)		0/210 (0%)		0/105 (0%)
Serious Adverse Events
	Test Product		Reference Product		Placebo Product
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/204 (2%)		1/210 (0.5%)		1/105 (1%)
Cardiac disorders
Sudden Death, Probable Myocardial Infarction	1/204 (0.5%)	1	0/210 (0%)	0	0/105 (0%)	0
Infections and infestations
Sepsis	1/204 (0.5%)	1	0/210 (0%)	0	0/105 (0%)	0
Acute Gastroenteritis/Food Poisoning	0/204 (0%)	0	1/210 (0.5%)	1	0/105 (0%)	0
Acute Sigmoid Diverticulitis/Colitis	0/204 (0%)	0	0/210 (0%)	0	1/105 (1%)	1
Musculoskeletal and connective tissue disorders
Worsening of Right Hip Osteoarthritis	1/204 (0.5%)	1	0/210 (0%)	0	0/105 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Left Breast Cancer	1/204 (0.5%)	1	0/210 (0%)	0	0/105 (0%)	0
Other (Not Including Serious) Adverse Events
	Test Product		Reference Product		Placebo Product
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/204 (5.4%)		14/210 (6.7%)		0/105 (0%)
General disorders
APPLICATION SITE PAIN	11/204 (5.4%)	11	14/210 (6.7%)	14	0/105 (0%)	0
APPLICATION SITE Pruritus	7/204 (3.4%)	7	11/210 (5.2%)	11	0/105 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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