Comparative Safety and Efficacy of Two Rosacea Products in the Treatment of Facial Erythema of Rosacea

• Sponsor: Padagis LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02385240
• Collaborator: (none)
• Enrollment: 552
• Arms: 3
• Duration (Months): 9

Study Details

Study Description

Brief Summary

To compare safety and efficacy of Perrigo's rosacea drug product compared to an FDA approved rosacea drug product in the treatment of facial erythema of rosacea.

Condition or Disease	Intervention/Treatment	Phase
Rosacea	Drug: Brimonidine Topical Gel, 0.33 percent (Perrigo); Drug: Brimonidine Topical Gel, 0.33 percent (Reference); Drug: Placebo gel	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 552 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Study Start Date: Mar 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 Brimonidine Topical Gel, 0.33 percent	Drug: Brimonidine Topical Gel, 0.33 percent (Perrigo); Other Names: Perrigo product
Active Comparator: Reference Product Brimonidine Topical Gel, 0.33 percent (Reference)	Drug: Brimonidine Topical Gel, 0.33 percent (Reference); Other Names: Reference Listed Drug Product
Placebo Comparator: Placebo gel Placebo	Drug: Placebo gel

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects With Composite Success [Day 15 at hour 6]

   2-grade improvement on both the Clinician's Erythema Assessment (CEA) and the Patient Self Assessment (PSA) scales

Secondary Outcome Measures

1. Proportion of Subjects With Composite Success [Day 15 at hour 3]

   2-grade improvement on both the Clinician's Erythema Assessment (CEA) and the Patient Self Assessment (PSA) scales

2. Proportion of Subjects With Composite Success [Day 15 at hour 9]

   2-grade improvement on both the Clinician's Erythema Assessment (CEA) and the Patient Self Assessment (PSA) scales

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Provide IRB approved written informed consent/assent.

2. Male or non-pregnant female, ≥ 18 years of age.

3. Diagnosis of rosacea with moderate to severe erythema on the face defined as: a score of ≥ 3 on the Clinician's Erythema Assessment (CEA) and a score of ≥ 3 on the Patient's Self-Assessment (PSA) on Visit 1/Day 1 (Baseline) prior to the first application of study medication at hour 0.

4. Willing and able to understand and comply with the requirements of the study.

5. Be in general good health and free from any clinically significant disease, other than rosacea, that might interfere with the study evaluations.

6. Females of childbearing potential in addition to having a negative urine pregnancy test, must be willing to use an acceptable form of birth control during the study

Exclusion Criteria:

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

2. Presence of three (3) or more facial inflammatory lesions of rosacea.

3. Current diagnosis of Raynaud's syndrome, thromboangiitis obliterans, orthostatic hypotension, severe cardiovascular disease, cerebral or coronary insufficiency, renal or hepatic impairment, scleroderma, Sjögren's syndrome or depression.

4. Other facial conditions that in the Investigator's opinion might interfere with a rosacea diagnosis and/or assessment including but not limited to: acne conglobata, acne fulminans, rhinophyma, facial pustulosis of the chin, peri-oral dermatitis, demodicidosis, facial keratosis pilaris, seborrheic dermatitis, acute lupus erythematosus, actinic keratosis, acne, dermatitis, psoriasis, squamous cell carcinoma, eczema, acneiform eruptions caused by medications, steroid acne, steroid folliculitis, or bacterial folliculitis .

5. Any uncontrolled, chronic or serious disease or medical condition that would prevent participation in a clinical trial or, in the judgment of the Investigator, would put the subject at undue risk or might confound the study assessments (such as planned hospitalization during the study).

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

7. Excessive facial hair (such as beards, sideburns, moustaches, etc.) that would interfere with diagnosis or assessment of rosacea.

8. History of hypersensitivity or allergy to any ingredient in the study medication.

9. Previous enrollment in this study.

10. Non-responders to prior treatment with topical brimonidine.

11. Currently using any product containing brimonidine tartrate or oxymetazoline.

12. Start or change of dose of hormonal treatments.

13. Start or change of dose of tricyclic or tetracyclic antidepressants, cardio glycosides, beta blockers or calcium channel blockers or other anti-hypertensive agents 3 months (90 days) prior to baseline or throughout the study. Use of such therapy must remain constant during the study.

14. Current treatment with or start of any of the following class of drugs: monoamine oxidase (MAO) inhibitors, barbiturates, opiates, sedatives, systemic anesthetics or alpha-agonists, medicines for psychosis, medicines for hyperactivity

15. Use within 6 months (180 days) prior to baseline or during the study of oral retinoids or therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed).

16. Use within 12 weeks (84 days) prior to baseline or during the study of systemic immunomodulators

17. Use of medicated make-up throughout the study and/or significant change in the use of consumer products within 4 weeks (28 days) of study entry and throughout the study.

18. Participation in any clinical study involving an investigational product or device in the 4 weeks (28 days) prior to baseline or throughout the study.

19. Use of following topicals on the face within 14 days prior to baseline or during the study of antibiotics and/or prescription anti-inflammatory agents including ophthalmic

20. Over the counter (OTC) topical anti-acne medications 7 days prior to baseline

21. Chronic, daily use of OTC anti-inflammatory medications for more than 7 days (does not include low-dose aspirin for cardiac prophylaxis), 7 days prior to baseline and throughout the study. Subjects may use acetaminophen for pain relief, as needed throughout the study.

22. Use of tanning booths, sun lamps, sunbathing, phototherapy or excessive ultraviolet (UV) exposure to the sun 7 days prior to baseline and throughout the study.

23. Use of Niacin ≥500 mg per day within 7 days of study start and throughout the study.

24. Use of topical astringents or abrasives within 2 days of study start and throughout the study.

25. Use of antipruritics (including antihistamines), spa treatments or chlorine exposure (swimming, etc.) within 24 hours of all study visits (Visit 1 through Visit 3).

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Padagis LLC

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 19, 2015
• Statistical Analysis Plan - Mar 19, 2015

More Information

Publications

None provided.

• Responsible Party: Padagis LLC
• ClinicalTrials.gov Identifier: NCT02385240
• Other Study ID Numbers: PRG-NY-14-022
• First Posted: Mar 11, 2015
• Last Update Posted: Oct 22, 2021
• Last Verified: Oct 1, 2021

• Additional relevant MeSH terms: Rosacea; Brimonidine Tartrate

Study Results

Participant Flow

Arm/Group Title	Test Product	Reference Product	Placebo Gel
Arm/Group Description	Brimonidine Topical Gel, 0.33 percent Brimonidine Topical Gel, 0.33 percent (Perrigo)	Brimonidine Topical Gel, 0.33 percent (Reference) Brimonidine Topical Gel, 0.33 percent (Reference)	Placebo Placebo gel
Period Title: Overall Study
STARTED	183	184	185
COMPLETED	182	178	184
NOT COMPLETED	1	6	1

Baseline Characteristics

Arm/Group Title	Test Product	Reference Product	Placebo Gel	Total
Arm/Group Description	Brimonidine Topical Gel, 0.33 percent Brimonidine Topical Gel, 0.33 percent (Perrigo)	Brimonidine Topical Gel, 0.33 percent (Reference) Brimonidine Topical Gel, 0.33 percent (Reference)	Placebo Placebo gel	Total of all reporting groups
Overall Participants	183	184	185	552
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.4 (12.5)	51.2 (13.29)	50.9 (12.27)	50.8 (12.67)
Sex: Female, Male (Count of Participants)
Female	138 75.4%	156 84.8%	137 74.1%	431 78.1%
Male	45 24.6%	28 15.2%	48 25.9%	121 21.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 13.1%	29 15.8%	18 9.7%	71 12.9%
Not Hispanic or Latino	159 86.9%	155 84.2%	167 90.3%	481 87.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.5%	0 0%	1 0.5%	2 0.4%
Asian	1 0.5%	0 0%	2 1.1%	3 0.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	181 98.9%	184 100%	181 97.8%	546 98.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 0.5%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects With Composite Success
Description	2-grade improvement on both the Clinician's Erythema Assessment (CEA) and the Patient Self Assessment (PSA) scales
Time Frame	Day 15 at hour 6

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Test Product	Reference Product	Placebo Gel
Arm/Group Description	Brimonidine Topical Gel, 0.33 percent Brimonidine Topical Gel, 0.33 percent (Perrigo)	Brimonidine Topical Gel, 0.33 percent (Reference) Brimonidine Topical Gel, 0.33 percent (Reference)	Placebo Placebo gel
Measure Participants	168	170	179
Count of Participants [Participants]	60 32.8%	58 31.5%	23 12.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Product, Reference Product
	Comments
	Type of Statistical Test	Equivalence
	Comments	provides 85% power of success
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Equivalence ratio
	Estimated Value	1.034
	Confidence Interval	(2-Sided) 90%; -7.52 to 10.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Subjects With Composite Success
Description	2-grade improvement on both the Clinician's Erythema Assessment (CEA) and the Patient Self Assessment (PSA) scales
Time Frame	Day 15 at hour 3

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Test Product	Reference Product	Placebo Gel
Arm/Group Description	Brimonidine Topical Gel, 0.33 percent Brimonidine Topical Gel, 0.33 percent (Perrigo)	Brimonidine Topical Gel, 0.33 percent (Reference) Brimonidine Topical Gel, 0.33 percent (Reference)	Placebo Placebo gel
Measure Participants	168	170	179
Count of Participants [Participants]	61 33.3%	58 31.5%	19 10.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Product, Reference Product
	Comments
	Type of Statistical Test	Equivalence
	Comments	provides 85% power of success
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Equivalence ratio
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 90%; -6.94 to 11.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Proportion of Subjects With Composite Success
Description	2-grade improvement on both the Clinician's Erythema Assessment (CEA) and the Patient Self Assessment (PSA) scales
Time Frame	Day 15 at hour 9

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Test Product	Reference Product	Placebo Gel
Arm/Group Description	Brimonidine Topical Gel, 0.33 percent Brimonidine Topical Gel, 0.33 percent (Perrigo)	Brimonidine Topical Gel, 0.33 percent (Reference) Brimonidine Topical Gel, 0.33 percent (Reference)	Placebo Placebo gel
Measure Participants	168	170	179
Count of Participants [Participants]	53 29%	42 22.8%	18 9.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Product, Reference Product
	Comments
	Type of Statistical Test	Equivalence
	Comments	provides 85% power of success
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Equivalence ratio
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 90%; -1.77 to 15.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	15 days
Arm/Group Title	Test Product		Reference Product		Placebo Gel
Arm/Group Description	Brimonidine Topical Gel, 0.33 percent Brimonidine Topical Gel, 0.33 percent (Perrigo)		Brimonidine Topical Gel, 0.33 percent (Reference) Brimonidine Topical Gel, 0.33 percent (Reference)		Placebo Placebo gel
All Cause Mortality
	Test Product		Reference Product		Placebo Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/183 (0%)		0/184 (0%)		0/185 (0%)
Serious Adverse Events
	Test Product		Reference Product		Placebo Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/183 (0.5%)		0/184 (0%)		0/185 (0%)
Metabolism and nutrition disorders
Diabetic Ketoacidosis	1/183 (0.5%)	1	0/184 (0%)	0	0/185 (0%)	0
Other (Not Including Serious) Adverse Events
	Test Product		Reference Product		Placebo Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/183 (0%)		0/184 (0%)		0/185 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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