Trial Outcomes & Findings for Evaluation of Relapse, Efficacy and Safety of Long-term Treatment With Oracea® vs Placebo (NCT NCT01426269)
NCT ID: NCT01426269
Last Updated: 2022-08-01
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
235 participants
Primary outcome timeframe
Period 2 (40 weeks)
Results posted on
2022-08-01
Participant Flow
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.
Participant milestones
| Measure |
Doxycycline and Metronidazole Regimen
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
|
Oral 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)
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
|
Placebo
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 1: 12 Weeks
STARTED
|
235
|
0
|
0
|
|
Period 1: 12 Weeks
COMPLETED
|
180
|
0
|
0
|
|
Period 1: 12 Weeks
NOT COMPLETED
|
55
|
0
|
0
|
|
Eligibility for Period 2, Randomization
STARTED
|
180
|
0
|
0
|
|
Eligibility for Period 2, Randomization
COMPLETED
|
130
|
0
|
0
|
|
Eligibility for Period 2, Randomization
NOT COMPLETED
|
50
|
0
|
0
|
|
Period 2: 40 Weeks
STARTED
|
0
|
65
|
65
|
|
Period 2: 40 Weeks
COMPLETED
|
0
|
27
|
18
|
|
Period 2: 40 Weeks
NOT COMPLETED
|
0
|
38
|
47
|
Reasons for withdrawal
| Measure |
Doxycycline and Metronidazole Regimen
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
|
Oral 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)
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
|
Placebo
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 1: 12 Weeks
Adverse Event
|
5
|
0
|
0
|
|
Period 1: 12 Weeks
Withdrawal by Subject
|
22
|
0
|
0
|
|
Period 1: 12 Weeks
Protocol Violation
|
5
|
0
|
0
|
|
Period 1: 12 Weeks
Lost to Follow-up
|
22
|
0
|
0
|
|
Period 1: 12 Weeks
Pregnancy
|
1
|
0
|
0
|
|
Eligibility for Period 2, Randomization
Did not qualify
|
42
|
0
|
0
|
|
Eligibility for Period 2, Randomization
Qualified, opted out
|
8
|
0
|
0
|
|
Period 2: 40 Weeks
Adverse Event
|
0
|
1
|
2
|
|
Period 2: 40 Weeks
Withdrawal by Subject
|
0
|
9
|
11
|
|
Period 2: 40 Weeks
Protocol Violation
|
0
|
5
|
5
|
|
Period 2: 40 Weeks
Lost to Follow-up
|
0
|
8
|
6
|
|
Period 2: 40 Weeks
Site closed
|
0
|
6
|
5
|
|
Period 2: 40 Weeks
Relapsed
|
0
|
9
|
18
|
Baseline Characteristics
Evaluation of Relapse, Efficacy and Safety of Long-term Treatment With Oracea® vs Placebo
Baseline characteristics by cohort
| Measure |
Period 1: Oral Doxycycline and Topical Metronidazole
n=230 Participants
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
|
|---|---|
|
Age, Continuous
|
47.4 years
STANDARD_DEVIATION 12.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
164 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
66 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
217 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
44 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
186 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
230 participants
n=5 Participants
|
|
Skin Type
Dry
|
40 participants
n=5 Participants
|
|
Skin Type
Normal
|
50 participants
n=5 Participants
|
|
Skin Type
Oily
|
38 participants
n=5 Participants
|
|
Skin Type
Combination
|
102 participants
n=5 Participants
|
|
FItzpatrick Skin Type
I
|
16 participants
n=5 Participants
|
|
FItzpatrick Skin Type
II
|
93 participants
n=5 Participants
|
|
FItzpatrick Skin Type
III
|
64 participants
n=5 Participants
|
|
FItzpatrick Skin Type
IV
|
42 participants
n=5 Participants
|
|
FItzpatrick Skin Type
V
|
15 participants
n=5 Participants
|
|
FItzpatrick Skin Type
VI
|
0 participants
n=5 Participants
|
|
History of Rosacea
|
4.4 years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
|
Height
|
66.0 inches
STANDARD_DEVIATION 3.8 • n=5 Participants
|
|
Weight
|
180.2 pounds
STANDARD_DEVIATION 45.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Oral Doxycycline
n=65 Participants
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
|
Placebo
n=65 Participants
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
|
Week 8
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)
|
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)
|
|---|---|---|---|---|
|
Period 2: Number of Subjects Who Relapsed
Week 4
|
4 participants
|
10 participants
|
—
|
—
|
|
Period 2: Number of Subjects Who Relapsed
Week 8
|
8 participants
|
14 participants
|
—
|
—
|
|
Period 2: Number of Subjects Who Relapsed
Week 12
|
9 participants
|
16 participants
|
—
|
—
|
|
Period 2: Number of Subjects Who Relapsed
Week 16
|
9 participants
|
16 participants
|
—
|
—
|
|
Period 2: Number of Subjects Who Relapsed
Week 20
|
9 participants
|
16 participants
|
—
|
—
|
|
Period 2: Number of Subjects Who Relapsed
Week 24
|
9 participants
|
17 participants
|
—
|
—
|
|
Period 2: Number of Subjects Who Relapsed
Week 28
|
9 participants
|
18 participants
|
—
|
—
|
|
Period 2: Number of Subjects Who Relapsed
Week 32
|
9 participants
|
18 participants
|
—
|
—
|
|
Period 2: Number of Subjects Who Relapsed
Week 36
|
9 participants
|
18 participants
|
—
|
—
|
|
Period 2: Number of Subjects Who Relapsed
Week 40
|
9 participants
|
18 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Oral Doxycycline
n=65 Participants
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
|
Placebo
n=65 Participants
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
|
Week 8
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)
|
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)
|
|---|---|---|---|---|
|
Period 2: Investigator's Global Assessment Success
Week 4
|
44 participants
|
38 participants
|
—
|
—
|
|
Period 2: Investigator's Global Assessment Success
Week 8
|
36 participants
|
33 participants
|
—
|
—
|
|
Period 2: Investigator's Global Assessment Success
Week 12
|
33 participants
|
37 participants
|
—
|
—
|
|
Period 2: Investigator's Global Assessment Success
Week 16
|
38 participants
|
34 participants
|
—
|
—
|
|
Period 2: Investigator's Global Assessment Success
Week 20
|
35 participants
|
33 participants
|
—
|
—
|
|
Period 2: Investigator's Global Assessment Success
Week 24
|
36 participants
|
32 participants
|
—
|
—
|
|
Period 2: Investigator's Global Assessment Success
Week 28
|
39 participants
|
35 participants
|
—
|
—
|
|
Period 2: Investigator's Global Assessment Success
Week 32
|
39 participants
|
34 participants
|
—
|
—
|
|
Period 2: Investigator's Global Assessment Success
Week 36
|
40 participants
|
33 participants
|
—
|
—
|
|
Period 2: Investigator's Global Assessment Success
Week 40
|
41 participants
|
33 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Oral Doxycycline
n=65 Participants
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
|
Placebo
n=65 Participants
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
|
Week 8
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)
|
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)
|
|---|---|---|---|---|
|
Period 2: Clinician's Erythema Assessment
Week 20
|
4.3 units on a scale
Standard Deviation 3.4
|
5.5 units on a scale
Standard Deviation 3.8
|
—
|
—
|
|
Period 2: Clinician's Erythema Assessment
Week 24
|
4.4 units on a scale
Standard Deviation 3.5
|
5.3 units on a scale
Standard Deviation 3.8
|
—
|
—
|
|
Period 2: Clinician's Erythema Assessment
Week 28
|
4.3 units on a scale
Standard Deviation 3.5
|
5.3 units on a scale
Standard Deviation 3.8
|
—
|
—
|
|
Period 2: Clinician's Erythema Assessment
Week 32
|
4.2 units on a scale
Standard Deviation 3.6
|
5.3 units on a scale
Standard Deviation 3.9
|
—
|
—
|
|
Period 2: Clinician's Erythema Assessment
Week 36
|
4.4 units on a scale
Standard Deviation 3.6
|
5.3 units on a scale
Standard Deviation 3.8
|
—
|
—
|
|
Period 2: Clinician's Erythema Assessment
Week 40
|
4.4 units on a scale
Standard Deviation 3.5
|
5.3 units on a scale
Standard Deviation 3.9
|
—
|
—
|
|
Period 2: Clinician's Erythema Assessment
Week 4
|
5.0 units on a scale
Standard Deviation 3.1
|
5.6 units on a scale
Standard Deviation 3.8
|
—
|
—
|
|
Period 2: Clinician's Erythema Assessment
Week 8
|
4.9 units on a scale
Standard Deviation 3.5
|
5.8 units on a scale
Standard Deviation 3.9
|
—
|
—
|
|
Period 2: Clinician's Erythema Assessment
Week 12
|
4.7 units on a scale
Standard Deviation 3.4
|
5.3 units on a scale
Standard Deviation 4.3
|
—
|
—
|
|
Period 2: Clinician's Erythema Assessment
Week 16
|
4.7 units on a scale
Standard Deviation 3.4
|
5.2 units on a scale
Standard Deviation 3.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Period 2 (40 Weeks)The evaluator (investigator or a designee) performed lesion counts at each postbaseline visit.
Outcome measures
| Measure |
Oral Doxycycline
n=65 Participants
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
|
Placebo
n=65 Participants
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
|
Week 8
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)
|
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)
|
|---|---|---|---|---|
|
Period 2: Inflammatory Lesion Count
Week 4
|
2.8 lesions
Standard Deviation 4.5
|
5.8 lesions
Standard Deviation 8.7
|
—
|
—
|
|
Period 2: Inflammatory Lesion Count
Week 8
|
3.1 lesions
Standard Deviation 4.1
|
4.3 lesions
Standard Deviation 6.0
|
—
|
—
|
|
Period 2: Inflammatory Lesion Count
Week 12
|
3.0 lesions
Standard Deviation 4.2
|
1.9 lesions
Standard Deviation 2.7
|
—
|
—
|
|
Period 2: Inflammatory Lesion Count
Week 16
|
2.4 lesions
Standard Deviation 4.0
|
2.3 lesions
Standard Deviation 2.6
|
—
|
—
|
|
Period 2: Inflammatory Lesion Count
Week 20
|
2.1 lesions
Standard Deviation 2.2
|
2.6 lesions
Standard Deviation 3.1
|
—
|
—
|
|
Period 2: Inflammatory Lesion Count
Week 24
|
2.2 lesions
Standard Deviation 2.7
|
2.9 lesions
Standard Deviation 3.9
|
—
|
—
|
|
Period 2: Inflammatory Lesion Count
Week 28
|
2.2 lesions
Standard Deviation 2.8
|
2.9 lesions
Standard Deviation 4.0
|
—
|
—
|
|
Period 2: Inflammatory Lesion Count
Week 32
|
2.2 lesions
Standard Deviation 3.0
|
2.4 lesions
Standard Deviation 3.3
|
—
|
—
|
|
Period 2: Inflammatory Lesion Count
Week 36
|
2.5 lesions
Standard Deviation 3.1
|
2.2 lesions
Standard Deviation 3.0
|
—
|
—
|
|
Period 2: Inflammatory Lesion Count
Week 40
|
2.1 lesions
Standard Deviation 2.6
|
1.6 lesions
Standard Deviation 1.9
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 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.
Outcome measures
| Measure |
Oral Doxycycline
n=235 Participants
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
|
Placebo
n=235 Participants
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
|
Week 8
n=235 Participants
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)
|
Week 12
n=235 Participants
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)
|
|---|---|---|---|---|
|
Period 1: Tolerability (Scaling)
None
|
103 participants
|
136 participants
|
139 participants
|
143 participants
|
|
Period 1: Tolerability (Scaling)
Mild
|
85 participants
|
58 participants
|
44 participants
|
23 participants
|
|
Period 1: Tolerability (Scaling)
Moderate
|
44 participants
|
24 participants
|
11 participants
|
2 participants
|
|
Period 1: Tolerability (Scaling)
Severe
|
3 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Period 1: Tolerability (Scaling)
Missing
|
0 participants
|
17 participants
|
41 participants
|
67 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 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.
Outcome measures
| Measure |
Oral Doxycycline
n=235 Participants
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
|
Placebo
n=235 Participants
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
|
Week 8
n=235 Participants
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)
|
Week 12
n=235 Participants
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)
|
|---|---|---|---|---|
|
Period 1: Tolerability (Stinging/Burning)
None
|
90 participants
|
135 participants
|
139 participants
|
143 participants
|
|
Period 1: Tolerability (Stinging/Burning)
Mild
|
71 participants
|
51 participants
|
44 participants
|
19 participants
|
|
Period 1: Tolerability (Stinging/Burning)
Moderate
|
60 participants
|
31 participants
|
11 participants
|
6 participants
|
|
Period 1: Tolerability (Stinging/Burning)
Severe
|
14 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Period 1: Tolerability (Stinging/Burning)
Missing
|
0 participants
|
17 participants
|
41 participants
|
67 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 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.
Outcome measures
| Measure |
Oral Doxycycline
n=235 Participants
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
|
Placebo
n=235 Participants
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
|
Week 8
n=235 Participants
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)
|
Week 12
n=235 Participants
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)
|
|---|---|---|---|---|
|
Period 1: Tolerability (Dryness)
None
|
76 participants
|
106 participants
|
120 participants
|
125 participants
|
|
Period 1: Tolerability (Dryness)
Mild
|
89 participants
|
78 participants
|
61 participants
|
37 participants
|
|
Period 1: Tolerability (Dryness)
Moderate
|
60 participants
|
32 participants
|
13 participants
|
6 participants
|
|
Period 1: Tolerability (Dryness)
Severe
|
10 participants
|
2 participants
|
0 participants
|
0 participants
|
|
Period 1: Tolerability (Dryness)
Missing
|
0 participants
|
17 participants
|
41 participants
|
67 participants
|
Adverse Events
Period 1: Oral Doxycycline and Topical Metronidazole
Serious events: 4 serious events
Other events: 9 other events
Deaths: 0 deaths
Period 2: Oral Doxycycline
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Period 2: Placebo
Serious events: 2 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Period 1: Oral Doxycycline and Topical Metronidazole
n=235 participants at risk
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
|
Period 2: Oral Doxycycline
n=65 participants at risk
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
|
Period 2: Placebo
n=65 participants at risk
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
|
|---|---|---|---|
|
Infections and infestations
Diverticulitis
|
0.43%
1/235 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
0.43%
1/235 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Nervous system disorders
Headache
|
0.43%
1/235 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Surgical and medical procedures
Thyroidectomy
|
0.43%
1/235 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Infections and infestations
Cellulitis
|
0.00%
0/235 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
1.5%
1/65 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Infections and infestations
Infected bites
|
0.00%
0/235 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
1.5%
1/65 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/235 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
1.5%
1/65 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Nervous system disorders
Presyncope
|
0.00%
0/235 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
1.5%
1/65 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/235 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
1.5%
1/65 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer stage 1
|
0.00%
0/235 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
1.5%
1/65 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
Other adverse events
| Measure |
Period 1: Oral Doxycycline and Topical Metronidazole
n=235 participants at risk
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
|
Period 2: Oral Doxycycline
n=65 participants at risk
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
|
Period 2: Placebo
n=65 participants at risk
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
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.85%
2/235 • Number of events 2 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
3.1%
2/65 • Number of events 2 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Infections and infestations
Gastroenteritis viral
|
0.43%
1/235 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
3.1%
2/65 • Number of events 3 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Infections and infestations
Sinusitis
|
1.7%
4/235 • Number of events 4 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
1.5%
1/65 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
3.1%
2/65 • Number of events 2 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Infections and infestations
Upper respiratory
|
0.43%
1/235 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
1.5%
1/65 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
4.6%
3/65 • Number of events 3 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.43%
1/235 • Number of events 1 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
0.00%
0/65 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
3.1%
2/65 • Number of events 2 • Period 1 (12 weeks of treatment with oral doxycycline and topical metronidazole) and Period 2 (40 weeks of treatment with oral doxycycline or placebo)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60