Evaluation of Relapse, Efficacy and Safety of Long-term Treatment With Oracea® vs Placebo

• Sponsor: Galderma R&D (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01426269
• Collaborator: (none)
• Enrollment: 235
• Locations: 11
• Arms: 3
• Duration (Months): 21
• Patients Per Site: 21.4
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess relapse, efficacy and safety in subjects with rosacea during long-term treatment with either Oracea® or placebo, after an initial 12-week regimen of Oracea® and MetroGel® 1%.

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

Detailed Description

Adult subjects with moderate to severe papulopustular rosacea will receive Oracea® and MetroGel® 1% once daily during phase 1 (baseline to week 12) of the study. Subjects will be eligible to enter phase 2 of the study based upon improvements in the Investigator's Global Assessment (IGA) score. During phase 2, subjects will receive either Oracea® or placebo once daily for up to an additional 40 weeks. Subjects who relapse during phase 2 will be discontinued from the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 235 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evaluation of Relapse, Efficacy and Safety of Long-term Treatment With Oracea® Capsules Compared to Placebo After an Initial 12 Week Treatment Regimen With Oracea® and MetroGel® 1% in Adults With Rosacea
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Subjects will receive placebo during phase 2 (week 12 - week 52)	Drug: Placebo; During phase 2 (week 12 - week 52): placebo, oral, one capsule daily in the morning
Other: Doxycycline and Metronidazole Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)	Drug: Doxycycline; During phase 1 (baseline - week 12): Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning During phase 1 (baseline - week 12) and phase 2 (week 12 - week 52): Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads), oral, one capsule daily in the morning; Other Names: Oracea® Capsules 40 mg ; Drug: Metronidazole; During Phase 1: MetroGel 1% (metronidazole 1% gel), topical, apply a thin layer once daily to the affected area; Other Names: Metrogel 1%
Active Comparator: Doxycycline Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) during phase 2 (week 12 - week 52)	Drug: Doxycycline; During phase 1 (baseline - week 12): Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning During phase 1 (baseline - week 12) and phase 2 (week 12 - week 52): Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads), oral, one capsule daily in the morning; Other Names: Oracea® Capsules 40 mg

Outcome Measures

Primary Outcome Measures

1. Period 2: Number of Subjects Who Relapsed [Period 2 (40 weeks)]

   Subjects who relapsed during phase 2 were discontinued. Relapse was defined as meeting any one of the following criteria: A return to the baseline lesion count A return to the baseline IGA score The investigator determines that a change in rosacea treatment is warranted due to the subject's clinical condition. The numbers reported here are accumulative numbers for each arm.

Secondary Outcome Measures

1. Period 2: Investigator's Global Assessment Success [Period 2 (40 weeks)]

   The evaluator (investigator) assessed the severity of rosacea at baseline and each postbaseline visit using a 5 point Investigator's Global Assessment scale. Subjects scores were then dichotomized into success (clear or near clear score) or failure (mild, moderate, or severe score).

2. Period 2: Clinician's Erythema Assessment [Period 2 (40 Weeks)]

   The evaluator (investigator) assessed the severity of erythema at baseline and each postbaseline visit using a total erythema score. The erythema of 5 areas of the face (forehead, chin, nose, right cheek, left cheek) was scored using a 5 point Clinician's Erythema Assessment scale (0 = none, 1 = mild, 2 = moderate, 3 = significant, 4 = severe). The total of the 5 individual erythema scores scores was the total erythema score.

3. Period 2: Inflammatory Lesion Count [Period 2 (40 Weeks)]

   The evaluator (investigator or a designee) performed lesion counts at each postbaseline visit.

Other Outcome Measures

1. Period 1: Tolerability (Scaling) [Period 1 (12 Weeks)]

   Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole.

2. Period 1: Tolerability (Stinging/Burning) [Period 1 (12 Weeks)]

   Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole.

3. Period 1: Tolerability (Dryness) [Period 1 (12 Weeks)]

   Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is male or female aged 18 to 80 years inclusive.

• Subject with papulopustular rosacea (11 to 40 papules or pustules) and an IGA of moderate or severe.

• For subjects using medications to treat a concurrent medical condition, type and dose must have been stable for at least 90 days prior to study entry.

Exclusion Criteria:

• Female subjects who are pregnant, nursing or planning a pregnancy during the study.

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

• Subject uses or has recently used any medication which may interfere with the absorption, distribution, or elimination of study medications, or may interfere with the assessments of efficacy or safety of the study medications.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ATS Clinical Research	Santa Monica	California	United States	90404
2	Dadeland Dermatology	Coral Gables	Florida	United States	33134
3	Melissa L. F. Knuckles M.D., P.S.C.	Corbin	Kentucky	United States	40701
4	Dermatology Specialists Research	Louisville	Kentucky	United States	40202
5	Melissa L. F. Knuckles M.D., P.S.C.	Richmond	Kentucky	United States	40475
6	The Maryland Laser, Skin, and Vein Institute, LLC	Hunt Valley	Maryland	United States	21030
7	Grekin Skin Institute	Warren	Michigan	United States	48088
8	Hilary Baldwin	Brooklyn	New York	United States	11201
9	The Center for Dermatology at Linden Oaks	Rochester	New York	United States	14625
10	Brodell Medical, Inc.	Warren	Ohio	United States	44483
11	Center for Dermatology and Laser Surgery	Portland	Oregon	United States	97225

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: NCT01426269
• Other Study ID Numbers: US10183
• First Posted: Aug 31, 2011
• Last Update Posted: Aug 1, 2022
• Last Verified: Jul 1, 2014

• Additional relevant MeSH terms: Rosacea; Metronidazole; Doxycycline

Study Results

Participant Flow

Pre-assignment Detail	Subjects were treated with doxycycline or placebo for 52 weeks (Period 2) after a 12 week treatment regimen of doxycycline and metronidazole (Period 1). Subjects who completed period 1 with clear/near clear IGA, or achieved at least a 2 grade IGA improvement were eligible for period 2 of the study.

Arm/Group Title	Doxycycline and Metronidazole Regimen	Oral Doxycycline	Placebo
Arm/Group Description	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12) Oral Doxycycline and Topical Metronidazole: During phase 1 (baseline - week 12): Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning and MetroGel 1% (metronidazole 1% gel), topical, apply a thin layer once daily to the affected area. After Period 1, subjects who meet criteria for phase 2 will be randomized to receive doxycycline or placebo during phase 2	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) during phase 2 (week 12 - week 52) Oral Doxycycline: During phase 2 week 12 - week 52: Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning	Subjects will receive placebo during phase 2 (week 12 - week 52) Placebo: During phase 2 (week 12 - week 52): placebo, oral, one capsule daily in the morning
Period Title: Period 1: 12 Weeks
STARTED	235	0	0
COMPLETED	180	0	0
NOT COMPLETED	55	0	0
Period Title: Period 1: 12 Weeks
STARTED	180	0	0
COMPLETED	130	0	0
NOT COMPLETED	50	0	0
Period Title: Period 1: 12 Weeks
STARTED	0	65	65
COMPLETED	0	27	18
NOT COMPLETED	0	38	47

Baseline Characteristics

Arm/Group Title	Period 1: Oral Doxycycline and Topical Metronidazole
Arm/Group Description	Subjects will receive oral doxycycline and topical metronidazole during period 1 (12 weeks) Oral Doxycycline and Topical Metronidazole: period 1, Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning and MetroGel 1% (metronidazole 1% gel), topical, apply a thin layer once daily to the affected area
Overall Participants	230
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.4 (12.9)
Sex: Female, Male (Count of Participants)
Female	164 71.3%
Male	66 28.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 0.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 3%
White	217 94.3%
More than one race	5 2.2%
Unknown or Not Reported	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	44 19.1%
Not Hispanic or Latino	186 80.9%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	230 100%
Skin Type (participants) [Number]
Dry	40 17.4%
Normal	50 21.7%
Oily	38 16.5%
Combination	102 44.3%
FItzpatrick Skin Type (participants) [Number]
I	16 7%
II	93 40.4%
III	64 27.8%
IV	42 18.3%
V	15 6.5%
VI	0 0%
History of Rosacea (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.4 (7.7)
Height (inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [inches]	66.0 (3.8)
Weight (pounds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pounds]	180.2 (45.0)

Outcome Measures

1. Primary Outcome

Title	Period 2: Number of Subjects Who Relapsed
Description	Subjects who relapsed during phase 2 were discontinued. Relapse was defined as meeting any one of the following criteria: A return to the baseline lesion count A return to the baseline IGA score The investigator determines that a change in rosacea treatment is warranted due to the subject's clinical condition. The numbers reported here are accumulative numbers for each arm.
Time Frame	Period 2 (40 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Doxycycline	Placebo
Arm/Group Description	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) during period 2 (40 weeks) after 12 weeks of treatment with oral docycycline and topical metronidazole. Oral Doxycycline: During period 2, Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning	Subjects will receive placebo during period 2 (40 weeks) after 12 weeks of treatment with oral docycycline and topical metronidazole. Placebo: During period 2, placebo, oral, one capsule daily in the morning
Measure Participants	65	65
Week 4	4 1.7%	10 NaN
Week 8	8 3.5%	14 NaN
Week 12	9 3.9%	16 NaN
Week 16	9 3.9%	16 NaN
Week 20	9 3.9%	16 NaN
Week 24	9 3.9%	17 NaN
Week 28	9 3.9%	18 NaN
Week 32	9 3.9%	18 NaN
Week 36	9 3.9%	18 NaN
Week 40	9 3.9%	18 NaN

2. Secondary Outcome

Title	Period 2: Investigator's Global Assessment Success
Description	The evaluator (investigator) assessed the severity of rosacea at baseline and each postbaseline visit using a 5 point Investigator's Global Assessment scale. Subjects scores were then dichotomized into success (clear or near clear score) or failure (mild, moderate, or severe score).
Time Frame	Period 2 (40 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Doxycycline	Placebo
Arm/Group Description	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) during period 2 (40 weeks) after 12 weeks of treatment with oral docycycline and topical metronidazole. Oral Doxycycline: During period 2, Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning	Subjects will receive placebo during period 2 (40 weeks) after 12 weeks of treatment with oral docycycline and topical metronidazole. Placebo: During period 2, placebo, oral, one capsule daily in the morning
Measure Participants	65	65
Week 4	44 19.1%	38 NaN
Week 8	36 15.7%	33 NaN
Week 12	33 14.3%	37 NaN
Week 16	38 16.5%	34 NaN
Week 20	35 15.2%	33 NaN
Week 24	36 15.7%	32 NaN
Week 28	39 17%	35 NaN
Week 32	39 17%	34 NaN
Week 36	40 17.4%	33 NaN
Week 40	41 17.8%	33 NaN

3. Secondary Outcome

Title	Period 2: Clinician's Erythema Assessment
Description	The evaluator (investigator) assessed the severity of erythema at baseline and each postbaseline visit using a total erythema score. The erythema of 5 areas of the face (forehead, chin, nose, right cheek, left cheek) was scored using a 5 point Clinician's Erythema Assessment scale (0 = none, 1 = mild, 2 = moderate, 3 = significant, 4 = severe). The total of the 5 individual erythema scores scores was the total erythema score.
Time Frame	Period 2 (40 Weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Doxycycline	Placebo
Arm/Group Description	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) during period 2 (40 weeks) after 12 weeks of treatment with oral docycycline and topical metronidazole. Oral Doxycycline: During period 2, Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning	Subjects will receive placebo during period 2 (40 weeks) after 12 weeks of treatment with oral docycycline and topical metronidazole. Placebo: During period 2, placebo, oral, one capsule daily in the morning
Measure Participants	65	65
Week 4	5.0 (3.1)	5.6 (3.8)
Week 8	4.9 (3.5)	5.8 (3.9)
Week 12	4.7 (3.4)	5.3 (4.3)
Week 16	4.7 (3.4)	5.2 (3.8)
Week 20	4.3 (3.4)	5.5 (3.8)
Week 24	4.4 (3.5)	5.3 (3.8)
Week 28	4.3 (3.5)	5.3 (3.8)
Week 32	4.2 (3.6)	5.3 (3.9)
Week 36	4.4 (3.6)	5.3 (3.8)
Week 40	4.4 (3.5)	5.3 (3.9)

4. Secondary Outcome

Title	Period 2: Inflammatory Lesion Count
Description	The evaluator (investigator or a designee) performed lesion counts at each postbaseline visit.
Time Frame	Period 2 (40 Weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Doxycycline	Placebo
Arm/Group Description	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) during period 2 (40 weeks) after 12 weeks of treatment with oral docycycline and topical metronidazole. Oral Doxycycline: During period 2, Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning	Subjects will receive placebo during period 2 (40 weeks) after 12 weeks of treatment with oral docycycline and topical metronidazole. Placebo: During period 2, placebo, oral, one capsule daily in the morning
Measure Participants	65	65
Week 4	2.8 (4.5)	5.8 (8.7)
Week 8	3.1 (4.1)	4.3 (6.0)
Week 12	3.0 (4.2)	1.9 (2.7)
Week 16	2.4 (4.0)	2.3 (2.6)
Week 20	2.1 (2.2)	2.6 (3.1)
Week 24	2.2 (2.7)	2.9 (3.9)
Week 28	2.2 (2.8)	2.9 (4.0)
Week 32	2.2 (3.0)	2.4 (3.3)
Week 36	2.5 (3.1)	2.2 (3.0)
Week 40	2.1 (2.6)	1.6 (1.9)

5. Other Pre-specified Outcome

Title	Period 1: Tolerability (Scaling)
Description	Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole.
Time Frame	Period 1 (12 Weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	Week 4	Week 8	Week 12
Arm/Group Description	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)
Measure Participants	235	235	235	235
None	103 44.8%	136 NaN	139 NaN	143 NaN
Mild	85 37%	58 NaN	44 NaN	23 NaN
Moderate	44 19.1%	24 NaN	11 NaN	2 NaN
Severe	3 1.3%	0 NaN	0 NaN	0 NaN
Missing	0 0%	17 NaN	41 NaN	67 NaN

6. Other Pre-specified Outcome

Title	Period 1: Tolerability (Stinging/Burning)
Description	Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole.
Time Frame	Period 1 (12 Weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	Week 4	Week 8	Week 12
Arm/Group Description	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)
Measure Participants	235	235	235	235
None	90 39.1%	135 NaN	139 NaN	143 NaN
Mild	71 30.9%	51 NaN	44 NaN	19 NaN
Moderate	60 26.1%	31 NaN	11 NaN	6 NaN
Severe	14 6.1%	1 NaN	0 NaN	0 NaN
Missing	0 0%	17 NaN	41 NaN	67 NaN

7. Other Pre-specified Outcome

Title	Period 1: Tolerability (Dryness)
Description	Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole.
Time Frame	Period 1 (12 Weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	Week 4	Week 8	Week 12
Arm/Group Description	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)	Subjects will receive Oracea® (oral doxycycline 40 mg USP (30 mg immediate release and 10 mg delayed release beads)) and MetroGel® 1% (topical metronidazole) during phase 1 (baseline to week 12)
Measure Participants	235	235	235	235
None	76 33%	106 NaN	120 NaN	125 NaN
Mild	89 38.7%	78 NaN	61 NaN	37 NaN
Moderate	60 26.1%	32 NaN	13 NaN	6 NaN
Severe	10 4.3%	2 NaN	0 NaN	0 NaN
Missing	0 0%	17 NaN	41 NaN	67 NaN

Adverse Events

Time Frame	Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
Arm/Group Title	Period 1: Oral Doxycycline and Topical Metronidazole		Period 2: Oral Doxycycline		Period 2: Placebo
Arm/Group Description	Subjects will receive oral doxycycline and topical metronidazole during period 1 (12 weeks) Oral Doxycycline and Topical Metronidazole: period 1, Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning and MetroGel 1% (metronidazole 1% gel), topical, apply a thin layer once daily to the affected area		Subjects will receive oral doxycycline during period 2 (40 weeks) after 12 weeks of treatment with oral docycycline and topical metronidazole. Oral Doxycycline: period 2, Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning		Subjects will receive placebo during period 2 (40 weeks) after 12 weeks of treatment with oral docycycline and topical metronidazole. Placebo: period 2, placebo, oral, one capsule daily in the morning
All Cause Mortality
	Period 1: Oral Doxycycline and Topical Metronidazole		Period 2: Oral Doxycycline		Period 2: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Period 1: Oral Doxycycline and Topical Metronidazole		Period 2: Oral Doxycycline		Period 2: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/235 (1.7%)		2/65 (3.1%)		2/65 (3.1%)
Gastrointestinal disorders
Gastritis	0/235 (0%)	0	1/65 (1.5%)	1	0/65 (0%)	0
Infections and infestations
Diverticulitis	1/235 (0.4%)	1	0/65 (0%)	0	0/65 (0%)	0
Cellulitis	0/235 (0%)	0	1/65 (1.5%)	1	0/65 (0%)	0
Infected bites	0/235 (0%)	0	1/65 (1.5%)	1	0/65 (0%)	0
Musculoskeletal and connective tissue disorders
Pain in Extremity	1/235 (0.4%)	1	0/65 (0%)	0	0/65 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer stage 1	0/235 (0%)	0	0/65 (0%)	0	1/65 (1.5%)	1
Nervous system disorders
Headache	1/235 (0.4%)	1	0/65 (0%)	0	0/65 (0%)	0
Presyncope	0/235 (0%)	0	1/65 (1.5%)	1	0/65 (0%)	0
Grand mal convulsion	0/235 (0%)	0	0/65 (0%)	0	1/65 (1.5%)	1
Surgical and medical procedures
Thyroidectomy	1/235 (0.4%)	1	0/65 (0%)	0	0/65 (0%)	0
Other (Not Including Serious) Adverse Events
	Period 1: Oral Doxycycline and Topical Metronidazole		Period 2: Oral Doxycycline		Period 2: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/235 (3.8%)		6/65 (9.2%)		7/65 (10.8%)
Gastrointestinal disorders
Nausea	2/235 (0.9%)	2	2/65 (3.1%)	2	0/65 (0%)	0
Infections and infestations
Gastroenteritis viral	1/235 (0.4%)	1	2/65 (3.1%)	3	0/65 (0%)	0
Sinusitis	4/235 (1.7%)	4	1/65 (1.5%)	1	2/65 (3.1%)	2
Upper respiratory	1/235 (0.4%)	1	1/65 (1.5%)	1	3/65 (4.6%)	3
Skin and subcutaneous tissue disorders
Actinic keratosis	1/235 (0.4%)	1	0/65 (0%)	0	2/65 (3.1%)	2

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