Evaluation of Rosacea-related Inflammatory Biochemical Markers in Adult Skin When Treated With Oracea® vs Placebo

• Sponsor: Galderma R&D (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01308619
• Collaborator: (none)
• Enrollment: 170
• Locations: 10
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 17
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The objective of this study is to determine the clinical effects of doxycycline 40 mg (30 mg immediate release and 10 mg delayed release beads) capsules (Oracea®) as compared to placebo in the skin of adults with papulopustular rosacea and to identify a correlation, if any, with rosacea-related inflammatory markers.

Condition or Disease	Intervention/Treatment	Phase
Rosacea	Drug: Doxycycline; Other: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 170 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Evaluation of Rosacea-related Inflammatory Biochemical Markers in the Skin of Adults With Papulopustular Rosacea Treated With Daily Doxycycline 40 mg (30 mg Immediate Release / 10 mg Delayed Release Beads) Capsules
• Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Oracea® Doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules	Drug: Doxycycline; doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules, oral, one capsule daily in the morning; Other Names: Oracea®
Active Comparator: placebo placebo	Other: Placebo; Placebo, oral, one capsule daily in the morning

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Inflammatory Lesion Counts [baseline to week 12]

   Mean change in inflammatory lesion counts from baseline to week 12

Secondary Outcome Measures

1. Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 [baseline to week 12]

   Mean change from baseline to week 12 in biochemical markers of rosacea and expression in skin samples. A biological marker is a substance used as an indicator of a biological state such as rosacea. Biochemical markers are serine protease activity and expression, metalloprotease activity and expression, and production of leucine leucine-37 [LL-37] peptide.

2. Investigator's Global Assessment (IGA) Scores at Week 12 [Week 12]

   Number of participants in each category of the Investigator's Global Assessment (IGA) scores at week 12. Investigator's Global Assessment evaluates papules and pustules of rosacea on a scale from 0 - 4 (0 = Clear, 1 = Near Clear, 2 = Mild, 3 = Moderate and 4 = Severe) with 0 being best and 4 being worst.

3. Change From Baseline in Clinician's Erythema Assessment (CEA) Scores [baseline to week 12]

   Mean change in Clinician's Erythema Assessment (CEA) from baseline to week 12. Clinician's Erythema Assessment evaluates erythema on a scale from 0 - 4 (0 = None, 1 = Mild, 2 = Moderate, 3 = Significant and 4 = Severe) with 0 being best and 4 being worst.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is male or female aged 18 to 70 years inclusive

• Subject with papulopustular rosacea (5 to 40 papules or pustules)

Exclusion Criteria:

• Subject has any other active dermatological condition on face that may interfere with the conduct of the study

• Subject uses proton pump inhibitors for treatment of gastroesophageal reflux within 30 days prior to baseline visit or during the study

• Subject uses spironolactone within 30 days prior to baseline visit or during the study

• Subject requires chronic treatment (>14 days) with sulfa drugs, erythromycin, cephalosporins and quinolones within 30 days prior to baseline visit or during the study

• Subject has used tetracycline antibiotics within 30 days prior to baseline visit or during the study

• Subject has used penicillin antibiotics within 30 days prior to baseline visit or during the study

• Subject uses topical or oral dapsone

• Subject has had a change in hormonal therapy within 3 months of initiation of therapy or during the study

• Subject has used systemic immunosuppressants (e.g. corticosteroids, cyclosporine, imuran, biologics, mycophenolate mofetil) within 30 days prior to baseline visit. For subjects who have received treatment with biologics, treatment must have been discontinued within 90 days prior to baseline

• Subject has used any systemic therapy directed at improving rosacea, including antibiotics, within 30 days prior to baseline visit

• Subject has used systemic retinoids within 6 months of the baseline visit

• Subject takes niacin at a dosage of 500 mg or more per day

• Subject has used any topical rosacea therapy including topical antibiotics, topical retinoids, topical sodium sulfacetamide preparations, topical benzoyl peroxides, topical vasoconstricting agents (e.g., oxymetazoline) topical calcineurin inhibitors (e.g. tacrolimus, pimecrolimus) within 30 days prior to baseline visit

• Subject has been treated with another investigational drug or device within 30 days of baseline visit. For subjects who received experimental biologic treatment, treatment must have been discontinued within five half lives of the baseline visit.

• Subject has a known allergy to any of the components of the study products, and/or a known hypersensitivity to tetracyclines

• Subject is using a clinically significant concomitant drug (e.g., use of long term non-steroidal anti-inflammatory agents unless used only on a PRN basis less than 7 days per month)

• Subject has used vasodilators or an adrenergic blocking agent within 6 weeks of baseline visit (except subjects on stable dose for greater than 3 months)

• Subject has had laser or light therapy on the face within 3 months of the baseline visit

• Subject with active ocular rosacea and/or blepharitis/meibomianitis requiring systemic treatment by an ophthalmologist

• Subject with rhinophymatous rosacea

• Subject with a history of noncompliance with a treatment regimen

• Subject is at risk in terms of precautions, warnings, and contraindications (see package insert)

• Subject has previously failed to have improvement of rosacea with appropriate use of systemic tetracycline family of antibiotics

• Subjects with a recent history of alcohol and/or drug abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Burke Pharmaceutical Research	Hot Springs	Arkansas	United States	71913
2	Therapeutics Clinical Research	San Diego	California	United States	92123
3	Hudson Dermatology	Evansville	Indiana	United States	47714
4	The Indiana Clinical Trials Center	Plainfield	Indiana	United States	46168
5	Michigan Center for Research Corp	Clinton Township	Michigan	United States	48038
6	Skin Search of Rochester, Inc	Rochester	New York	United States	14623
7	Oregon Medical Research Center, PC	Portland	Oregon	United States	97223
8	Derm Research	Austin	Texas	United States	78759
9	J & S Studies, Inc.	College Station	Texas	United States	77845
10	Suzanne Bruce and Associates, PA	Houston	Texas	United States	77056

Sponsors and Collaborators

• Galderma R&D

Investigators

• Study Director: Ronald W Gottschalk, MD, Galderma R&D

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Galderma R&D
• ClinicalTrials.gov Identifier: NCT01308619
• Other Study ID Numbers: US10150
• First Posted: Mar 4, 2011
• Last Update Posted: Aug 1, 2022
• Last Verified: Jul 1, 2014

• Additional relevant MeSH terms: Rosacea; Doxycycline

Study Results

Participant Flow

Recruitment Details	First subject enrolled 9 May 2011, last subject last visit 2 July 2012

Arm/Group Title	Oracea®	Placebo Capsules
Arm/Group Description	Doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules for 12 weeks	Placebo capsules for 12 weeks
Period Title: Overall Study
STARTED	84	86
COMPLETED	77	83
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	Oracea®	Placebo	Total
Arm/Group Description	Doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules	placebo	Total of all reporting groups
Overall Participants	84	86	170
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.6 (11.4)	48.7 (10.8)	49.1 (11.1)
Sex: Female, Male (Count of Participants)
Female	61 72.6%	60 69.8%	121 71.2%
Male	23 27.4%	26 30.2%	49 28.8%
Region of Enrollment (participants) [Number]
United States	84 100%	86 100%	170 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Inflammatory Lesion Counts
Description	Mean change in inflammatory lesion counts from baseline to week 12
Time Frame	baseline to week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oracea®	Placebo
Arm/Group Description	Doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules	placebo
Measure Participants	84	86
Mean (Standard Deviation) [inflammatory lesions]	-4.3 (7.9)	-3.2 (8.6)

2. Secondary Outcome

Title	Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12
Description	Mean change from baseline to week 12 in biochemical markers of rosacea and expression in skin samples. A biological marker is a substance used as an indicator of a biological state such as rosacea. Biochemical markers are serine protease activity and expression, metalloprotease activity and expression, and production of leucine leucine-37 [LL-37] peptide.
Time Frame	baseline to week 12

Outcome Measure Data

Analysis Population Description

Treatment success was defined as all subjects from either treatment group with a score of clear or near clear on the Investigator's Global Assessment (IGA) scale. Treatment failure was defined as all subjects from either treatment group with a score of mild, moderate, or severe on the IGA scale.

Arm/Group Title	Treatment Success	Treatment Failure
Arm/Group Description
Measure Participants	49	111
Cathelicidin	-0.0931 (0.5491)	-0.0379 (0.1545)
KLK5	-0.0034 (0.0110)	-0.0049 (0.0146)
MMP9	-0.0017 (0.0100)	-0.0021 (0.0233)
Total Protease	-22351.6 (102888.2)	-22540.9 (66146.2)

3. Secondary Outcome

Title	Investigator's Global Assessment (IGA) Scores at Week 12
Description	Number of participants in each category of the Investigator's Global Assessment (IGA) scores at week 12. Investigator's Global Assessment evaluates papules and pustules of rosacea on a scale from 0 - 4 (0 = Clear, 1 = Near Clear, 2 = Mild, 3 = Moderate and 4 = Severe) with 0 being best and 4 being worst.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oracea®	Placebo
Arm/Group Description	Doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules	placebo
Measure Participants	84	86
Clear	8 9.5%	2 2.3%
Near Clear	23 27.4%	18 20.9%
Mild	35 41.7%	31 36%
Moderate	12 14.3%	20 23.3%
Severe	6 7.1%	15 17.4%

4. Secondary Outcome

Title	Change From Baseline in Clinician's Erythema Assessment (CEA) Scores
Description	Mean change in Clinician's Erythema Assessment (CEA) from baseline to week 12. Clinician's Erythema Assessment evaluates erythema on a scale from 0 - 4 (0 = None, 1 = Mild, 2 = Moderate, 3 = Significant and 4 = Severe) with 0 being best and 4 being worst.
Time Frame	baseline to week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oracea®	Placebo
Arm/Group Description	Doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules	placebo
Measure Participants	84	86
Mean (Standard Deviation) [units on a scale]	-1.0 (2.9)	-0.8 (3.1)

Adverse Events

Arm/Group Title	Oracea®		Placebo
Arm/Group Description	Doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules		placebo
All Cause Mortality
	Oracea®		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Oracea®		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/84 (2.4%)		0/86 (0%)
Cardiac disorders
Chest pain	1/84 (1.2%)	1	0/86 (0%)	0
Pregnancy, puerperium and perinatal conditions
Spontaneous abortion	1/84 (1.2%)	1	0/86 (0%)	0
Other (Not Including Serious) Adverse Events
	Oracea®		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/84 (9.5%)		6/86 (7%)
Gastrointestinal disorders
nausea	3/84 (3.6%)	4	1/86 (1.2%)	2
Infections and infestations
sinusitis	3/84 (3.6%)	3	2/86 (2.3%)	2
upper respiratory infection	2/84 (2.4%)	2	3/86 (3.5%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.