Safety and Efficacy of Oxymetazoline HCl Cream 1.0% in Patients With Persistent Erythema Associated With Rosacea

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02132117
• Collaborator: (none)
• Enrollment: 445
• Location: 1
• Arms: 2
• Duration (Months): 11
• Patients Per Site Per Month: 40.6

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of oxymetazoline hydrochloride (HCl) cream 1.0% (AGN-199201) once daily compared to vehicle for the treatment of persistent moderate to severe facial erythema associated with rosacea.

Condition or Disease	Intervention/Treatment	Phase
Erythema; Rosacea	Drug: Oxymetazoline HCL Cream 1.0%; Drug: Vehicle to Oxymetazoline HCL Cream	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 445 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oxymetazoline HCL Cream 1.0% Oxymetazoline HCL Cream 1.0% applied to the face once daily for 29 days.	Drug: Oxymetazoline HCL Cream 1.0%; Oxymetazoline HCL Cream 1.0% (AGN-199201) applied to the face once daily for 29 days.
Placebo Comparator: Vehicle Vehicle to Oxymetazoline HCL Cream applied to the face once daily for 29 days.	Drug: Vehicle to Oxymetazoline HCL Cream; Vehicle to Oxymetazoline HCL Cream (AGN-199201) applied to the face once daily for 29 days.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With at Least a 2-Grade Improvement (Decrease) From Baseline on Both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for Rosacea Facial Redness (SSA) 5-point Scales [Baseline, Day 29 (Hours 3, 6, 9 and 12)]

   The investigator assessed the participant's overall severity of erythema in the treatment area by using the 5-point CEA scale with photonumeric guide where: 0=clear skin with no signs of erythema (best) to 4=severe erythema; fiery redness (worst). A decrease in the score indicates improvement. The participant assessed their overall severity of rosacea facial redness in the treatment area by using the 5-point SSA scale with photoguide where: 0=no signs of unwanted redness (best) to 4=severe redness (worst). A decrease in the score indicates improvement. The percentage of participants with at least a 2-grade decrease (improvement) on both CEA and SSA from Baseline was evaluated over the 12-hour evaluation period (hours 3, 6, 9, and 12) post-dose on Day 29. Baseline was defined as the measurement at pre-dose on Day 1.

Secondary Outcome Measures

1. Percentage of Participants With at Least a 2-Grade Improvement (Decrease) From Baseline on SSA at Hours 3, 6, 9 and 12 on Day 29 [Baseline, Day 29 (Hours 3, 6, 9 and 12)]

   The participant assessed their overall severity of rosacea facial redness in the treatment area by using the 5-point SSA scale with photoguide where: 0=no signs of unwanted redness (best) to 4=severe redness (worst). A decrease in the score indicates improvement. The percentage of participants with at least a 2-grade decrease (improvement) on SSA from Baseline was evaluated over the 12-hour evaluation period (hours 3, 6, 9, and 12) post-dose on Day 29.

2. Percent Change From Baseline on Rosacea Facial Redness as Measured by Digital Imaging Analysis (DIA) at Hours 3, 6, 9 and 12 on Day 29 [Baseline, Day 29 (Hours 3, 6, 9 and 12)]

   DIA of photographs was used to assess rosacea facial redness and was defined as percentage of facial area occupied by redness. A higher value in the percentage of facial area occupied by facial redness indicated more redness. A negative/ lower number percent change from Baseline indicates improvement.

3. Percentage of Participants Satisfied or Very Satisfied on Item #9 of Satisfaction Assessment for Rosacea Facial Redness (SAT-RFR) at Hours 3, 6, 9 and 12 on Day 29 [Day 29 (Hours 3, 6, 9 and 12)]

   Participants assessed their treatment satisfaction by answering Item #9 of the SAT-RFR: "Right now, how satisfied are you with the effect your study medication had on your facial redness?" using a 5-point scale where 0= very dissatisfied, 1=dissatisfied, 2=neither satisfied or dissatisfied, 3=satisfied, or 4=very satisfied. The percentage of participants who answered Satisfied or Very Satisfied is reported.

4. Change From Baseline on the Symptom Assessment for Rosacea Facial Redness (SA-RFR) Item # 4 at Hours 3, 6, 9 and 12 on Day 29 [Baseline, Day 29 (Hours 3, 6, 9 and 12)]

   Participants assessed the burning sensation associated with rosacea facial redness by answering Item #4 of the SA-RFR: "Right now, how much does your face burn because of your facial redness?" using a 5-point scale where 0=less severe to 4=severe. A negative change from Baseline indicates improvement.

5. Percentage of Participants With at Least a 1-Grade Improvement (Decrease) From Baseline on SSA at Hour 1 on Day 1 [Baseline, Day 1 (Hour 1)]

   The participant assessed their overall severity of rosacea facial redness in the treatment area by using the 5-point SSA scale with photoguide where: 0=no signs of unwanted redness (best) to 4=severe redness (worst). A decrease in the score indicates improvement.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

-Moderate to severe persistent facial erythema associated with rosacea.

Exclusion Criteria:

• Greater than 3 inflammatory lesions on the face

• Current treatment with monoamine oxidase (MAO) inhibitors

• Raynaud's syndrome, narrow angle glaucoma, orthostatic hypotension, scleroderma or Sjogren's syndrome.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		College Station	Texas	United States

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02132117
• Other Study ID Numbers: 199201-005
• First Posted: May 7, 2014
• Last Update Posted: Nov 18, 2019
• Last Verified: Nov 1, 2019

• Additional relevant MeSH terms: Rosacea; Erythema; Phenylephrine; Oxymetazoline

Study Results

Participant Flow

Arm/Group Title	Oxymetazoline HCL Cream 1.0%	Vehicle
Arm/Group Description	Oxymetazoline hydrochloride (HCL) Cream 1.0% applied to the face once daily for 29 days.	Vehicle to Oxymetazoline HCL Cream applied to the face once daily for 29 days.
Period Title: Overall Study
STARTED	224	221
COMPLETED	213	216
NOT COMPLETED	11	5

Baseline Characteristics

Arm/Group Title	Oxymetazoline HCL Cream 1.0%	Vehicle	Total
Arm/Group Description	Oxymetazoline HCL Cream 1.0% applied to the face once daily for 29 days.	Vehicle to Oxymetazoline HCL Cream applied to the face once daily for 29 days.	Total of all reporting groups
Overall Participants	224	221	445
Age, Customized (participants) [Number]
18-64 years	198 88.4%	193 87.3%	391 87.9%
>=65 years	26 11.6%	28 12.7%	54 12.1%
Sex: Female, Male (Count of Participants)
Female	177 79%	173 78.3%	350 78.7%
Male	47 21%	48 21.7%	95 21.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With at Least a 2-Grade Improvement (Decrease) From Baseline on Both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for Rosacea Facial Redness (SSA) 5-point Scales
Description	The investigator assessed the participant's overall severity of erythema in the treatment area by using the 5-point CEA scale with photonumeric guide where: 0=clear skin with no signs of erythema (best) to 4=severe erythema; fiery redness (worst). A decrease in the score indicates improvement. The participant assessed their overall severity of rosacea facial redness in the treatment area by using the 5-point SSA scale with photoguide where: 0=no signs of unwanted redness (best) to 4=severe redness (worst). A decrease in the score indicates improvement. The percentage of participants with at least a 2-grade decrease (improvement) on both CEA and SSA from Baseline was evaluated over the 12-hour evaluation period (hours 3, 6, 9, and 12) post-dose on Day 29. Baseline was defined as the measurement at pre-dose on Day 1.
Time Frame	Baseline, Day 29 (Hours 3, 6, 9 and 12)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population included all randomized participants.

Arm/Group Title	Oxymetazoline HCL Cream 1.0%	Vehicle
Arm/Group Description	Oxymetazoline HCL Cream 1.0% applied to the face once daily for 29 days.	Vehicle to Oxymetazoline HCL Cream applied to the face once daily for 29 days.
Measure Participants	224	221
Day 29 (Hour 3)	14.3 6.4%	7.4 3.3%
Day 29 (Hour 6)	13.4 6%	4.8 2.2%
Day 29 (Hour 9)	15.5 6.9%	8.5 3.8%
Day 29 (Hour 12)	12.3 5.5%	6.1 2.8%

2. Secondary Outcome

Title	Percentage of Participants With at Least a 2-Grade Improvement (Decrease) From Baseline on SSA at Hours 3, 6, 9 and 12 on Day 29
Description	The participant assessed their overall severity of rosacea facial redness in the treatment area by using the 5-point SSA scale with photoguide where: 0=no signs of unwanted redness (best) to 4=severe redness (worst). A decrease in the score indicates improvement. The percentage of participants with at least a 2-grade decrease (improvement) on SSA from Baseline was evaluated over the 12-hour evaluation period (hours 3, 6, 9, and 12) post-dose on Day 29.
Time Frame	Baseline, Day 29 (Hours 3, 6, 9 and 12)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Oxymetazoline HCL Cream 1.0%	Vehicle
Arm/Group Description	Oxymetazoline HCL Cream 1.0% applied to the face once daily for 29 days.	Vehicle to Oxymetazoline HCL Cream applied to the face once daily for 29 days.
Measure Participants	224	221
Day 29 (Hour 3)	24.1 10.8%	15.8 7.1%
Day 29 (Hour 6)	24.8 11.1%	14.7 6.7%
Day 29 (Hour 9)	22.0 9.8%	16.0 7.2%
Day 29 (Hour 12)	23.7 10.6%	15.8 7.1%

3. Secondary Outcome

Title	Percent Change From Baseline on Rosacea Facial Redness as Measured by Digital Imaging Analysis (DIA) at Hours 3, 6, 9 and 12 on Day 29
Description	DIA of photographs was used to assess rosacea facial redness and was defined as percentage of facial area occupied by redness. A higher value in the percentage of facial area occupied by facial redness indicated more redness. A negative/ lower number percent change from Baseline indicates improvement.
Time Frame	Baseline, Day 29 (Hours 3, 6, 9 and 12)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Oxymetazoline HCL Cream 1.0%	Vehicle
Arm/Group Description	Oxymetazoline HCL Cream 1.0% applied to the face once daily for 29 days.	Vehicle to Oxymetazoline HCL Cream applied to the face once daily for 29 days.
Measure Participants	224	221
Day 29 (Hour 3)	-25.70 (144.776)	0.00 (225.452)
Day 29 (Hour 6)	-15.95 (170.735)	2.25 (198.138)
Day 29 (Hour 9)	-10.95 (131.933)	5.15 (200.530)
Day 29 (Hour 12)	-9.60 (145.898)	1.00 (195.291)

4. Secondary Outcome

Title	Percentage of Participants Satisfied or Very Satisfied on Item #9 of Satisfaction Assessment for Rosacea Facial Redness (SAT-RFR) at Hours 3, 6, 9 and 12 on Day 29
Description	Participants assessed their treatment satisfaction by answering Item #9 of the SAT-RFR: "Right now, how satisfied are you with the effect your study medication had on your facial redness?" using a 5-point scale where 0= very dissatisfied, 1=dissatisfied, 2=neither satisfied or dissatisfied, 3=satisfied, or 4=very satisfied. The percentage of participants who answered Satisfied or Very Satisfied is reported.
Time Frame	Day 29 (Hours 3, 6, 9 and 12)

Outcome Measure Data

Analysis Population Description

Participants from the ITT Population, all randomized participants with data available for analysis.

Arm/Group Title	Oxymetazoline HCL Cream 1.0%	Vehicle
Arm/Group Description	Oxymetazoline HCL Cream 1.0% applied to the face once daily for 29 days.	Vehicle to Oxymetazoline HCL Cream applied to the face once daily for 29 days.
Measure Participants	223	220
Day 29 (Hour 3)	54.3 24.2%	34.1 15.4%
Day 29 (Hour 6)	49.3 22%	32.3 14.6%
Day 29 (Hour 9)	49.8 22.2%	33.6 15.2%
Day 29 (Hour 12)	47.5 21.2%	36.4 16.5%

5. Secondary Outcome

Title	Change From Baseline on the Symptom Assessment for Rosacea Facial Redness (SA-RFR) Item # 4 at Hours 3, 6, 9 and 12 on Day 29
Description	Participants assessed the burning sensation associated with rosacea facial redness by answering Item #4 of the SA-RFR: "Right now, how much does your face burn because of your facial redness?" using a 5-point scale where 0=less severe to 4=severe. A negative change from Baseline indicates improvement.
Time Frame	Baseline, Day 29 (Hours 3, 6, 9 and 12)

Outcome Measure Data

Analysis Population Description

Participants from the ITT Population, all randomized participants, with data available for analysis at the given time-point. Only participants who had a SA-RFR score of 1-4 at Baseline are included in the Analysis.

Arm/Group Title	Oxymetazoline HCL Cream 1.0%	Vehicle
Arm/Group Description	Oxymetazoline HCL Cream 1.0% applied to the face once daily for 29 days.	Vehicle to Oxymetazoline HCL Cream applied to the face once daily for 29 days.
Measure Participants	129	134
Day 29 (Hour 3)	-1.8 (0.97)	-1.6 (0.93)
Day 29 (Hour 6)	-1.8 (0.93)	-1.6 (0.91)
Day 29 (Hour 9)	-1.8 (0.91)	-1.7 (0.96)
Day 29 (Hour 12)	-1.8 (0.92)	-1.7 (0.91)

6. Secondary Outcome

Title	Percentage of Participants With at Least a 1-Grade Improvement (Decrease) From Baseline on SSA at Hour 1 on Day 1
Description	The participant assessed their overall severity of rosacea facial redness in the treatment area by using the 5-point SSA scale with photoguide where: 0=no signs of unwanted redness (best) to 4=severe redness (worst). A decrease in the score indicates improvement.
Time Frame	Baseline, Day 1 (Hour 1)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants.

Arm/Group Title	Oxymetazoline HCL Cream 1.0%	Vehicle
Arm/Group Description	Oxymetazoline HCL Cream 1.0% applied to the face once daily for 29 days.	Vehicle to Oxymetazoline HCL Cream applied to the face once daily for 29 days.
Measure Participants	224	221
Number [percentage of participants]	29.7 13.3%	16.8 7.6%

Adverse Events

Adverse Event Reporting Description	Safety Population, all participants who applied at least one dose of study medication, was used to determine the number of participants at risk for Serious Adverse Events and Adverse Events.
Arm/Group Title	Oxymetazoline HCL Cream 1.0%		Vehicle
Arm/Group Description	Oxymetazoline HCL Cream 1.0% applied to the face once daily for 29 days.		Vehicle to Oxymetazoline HCL Cream applied to the face once daily for 29 days.
All Cause Mortality
	Oxymetazoline HCL Cream 1.0%		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Oxymetazoline HCL Cream 1.0%		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/223 (1.3%)		2/221 (0.9%)
Endocrine disorders
Goitre	0/223 (0%)		1/221 (0.5%)
Hyperparathyroidism	0/223 (0%)		1/221 (0.5%)
Injury, poisoning and procedural complications
Road traffic accident	1/223 (0.4%)		0/221 (0%)
Clavicle fracture	0/223 (0%)		1/221 (0.5%)
Concussion	0/223 (0%)		1/221 (0.5%)
Rib fracture	0/223 (0%)		1/221 (0.5%)
Spinal fracture	0/223 (0%)		1/221 (0.5%)
Traumatic liver injury	0/223 (0%)		1/221 (0.5%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/223 (0.4%)		0/221 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/223 (0.4%)		0/221 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/223 (0%)		1/221 (0.5%)
Other (Not Including Serious) Adverse Events
	Oxymetazoline HCL Cream 1.0%		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/223 (0%)		0/221 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.