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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01426269
Recruitment Status : Completed
First Posted : August 31, 2011
Results First Posted : August 4, 2014
Last Update Posted : August 4, 2014
Sponsor:
Information provided by (Responsible Party):
Galderma Laboratories, L.P.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rosacea
Interventions Drug: Doxycycline
Drug: Metronidazole
Drug: Placebo
Enrollment 235
Recruitment Details  
Pre-assignment Details 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
Hide 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
Reason Not Completed
Adverse Event             5             0             0
Withdrawal by Subject             22             0             0
Protocol Violation             5             0             0
Lost to Follow-up             22             0             0
Pregnancy             1             0             0
Period Title: Eligibility for Period 2, Randomization
Started 180 0 0
Completed 130 0 0
Not Completed 50 0 0
Reason Not Completed
Did not qualify             42             0             0
Qualified, opted out             8             0             0
Period Title: Period 2: 40 Weeks
Started 0 65 65
Completed 0 27 18
Not Completed 0 38 47
Reason Not Completed
Adverse Event             0             1             2
Withdrawal by Subject             0             9             11
Protocol Violation             0             5             5
Lost to Follow-up             0             8             6
Site closed             0             6             5
Relapsed             0             9             18
Arm/Group Title Period 1: Oral Doxycycline and Topical Metronidazole
Hide 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 Number of Baseline Participants 230
Hide Baseline Analysis Population Description
The safety population included 235 enrolled subjects. However, Baseline demographics were based on the ITT population which included 230 subjects; 5 subjects were excluded from this population due to consent issues.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 230 participants
47.4  (12.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants
Female
164
  71.3%
Male
66
  28.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   0.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
7
   3.0%
White
217
  94.3%
More than one race
5
   2.2%
Unknown or Not Reported
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants
Hispanic or Latino
44
  19.1%
Not Hispanic or Latino
186
  80.9%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 230 participants
230
Skin Type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 230 participants
Dry 40
Normal 50
Oily 38
Combination 102
FItzpatrick Skin Type   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 230 participants
I 16
II 93
III 64
IV 42
V 15
VI 0
[1]
Measure Description: Fitzpatrick Skin Type Classification Scale I, always burns easily; never tans II, always burns easily; tans minimally and with difficulty III, burns minimally; tans gradually and uniformly (light brown) IV, burns minimally; always tans well (moderate brown) V, rarely burns; tans very easily (dark brown) VI, never burns, tans very easily (black)
History of Rosacea  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 230 participants
4.4  (7.7)
Height  
Mean (Standard Deviation)
Unit of measure:  Inches
Number Analyzed 230 participants
66.0  (3.8)
Weight  
Mean (Standard Deviation)
Unit of measure:  Pounds
Number Analyzed 230 participants
180.2  (45.0)
1.Primary Outcome
Title Period 2: Number of Subjects Who Relapsed
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Doxycycline Placebo
Hide 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

Overall Number of Participants Analyzed 65 65
Measure Type: Number
Unit of Measure: participants
Week 4 4 10
Week 8 8 14
Week 12 9 16
Week 16 9 16
Week 20 9 16
Week 24 9 17
Week 28 9 18
Week 32 9 18
Week 36 9 18
Week 40 9 18
2.Secondary Outcome
Title Period 2: Investigator's Global Assessment Success
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Doxycycline Placebo
Hide 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

Overall Number of Participants Analyzed 65 65
Measure Type: Number
Unit of Measure: participants
Week 4 44 38
Week 8 36 33
Week 12 33 37
Week 16 38 34
Week 20 35 33
Week 24 36 32
Week 28 39 35
Week 32 39 34
Week 36 40 33
Week 40 41 33
3.Secondary Outcome
Title Period 2: Clinician's Erythema Assessment
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Doxycycline Placebo
Hide 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

Overall Number of Participants Analyzed 65 65
Mean (Standard Deviation)
Unit of Measure: units on a scale
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
Hide Description The evaluator (investigator or a designee) performed lesion counts at each postbaseline visit.
Time Frame Period 2 (40 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Doxycycline Placebo
Hide 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

Overall Number of Participants Analyzed 65 65
Mean (Standard Deviation)
Unit of Measure: lesions
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)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Baseline Week 4 Week 8 Week 12
Hide 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)
Overall Number of Participants Analyzed 235 235 235 235
Measure Type: Number
Unit of Measure: participants
None 103 136 139 143
Mild 85 58 44 23
Moderate 44 24 11 2
Severe 3 0 0 0
Missing 0 17 41 67
6.Other Pre-specified Outcome
Title Period 1: Tolerability (Stinging/Burning)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Baseline Week 4 Week 8 Week 12
Hide 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)
Overall Number of Participants Analyzed 235 235 235 235
Measure Type: Number
Unit of Measure: participants
None 90 135 139 143
Mild 71 51 44 19
Moderate 60 31 11 6
Severe 14 1 0 0
Missing 0 17 41 67
7.Other Pre-specified Outcome
Title Period 1: Tolerability (Dryness)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Baseline Week 4 Week 8 Week 12
Hide 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)
Overall Number of Participants Analyzed 235 235 235 235
Measure Type: Number
Unit of Measure: participants
None 76 106 120 125
Mild 89 78 61 37
Moderate 60 32 13 6
Severe 10 2 0 0
Missing 0 17 41 67
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)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Period 1: Oral Doxycycline and Topical Metronidazole Period 2: Oral Doxycycline Period 2: Placebo
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide 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 (1.70%)      2/65 (3.08%)      2/65 (3.08%)    
Gastrointestinal disorders       
Gastritis * 1  0/235 (0.00%)  0 1/65 (1.54%)  1 0/65 (0.00%)  0
Infections and infestations       
Diverticulitis * 1  1/235 (0.43%)  1 0/65 (0.00%)  0 0/65 (0.00%)  0
Cellulitis * 1  0/235 (0.00%)  0 1/65 (1.54%)  1 0/65 (0.00%)  0
Infected bites * 1  0/235 (0.00%)  0 1/65 (1.54%)  1 0/65 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Pain in Extremity * 1  1/235 (0.43%)  1 0/65 (0.00%)  0 0/65 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Endometrial cancer stage 1 * 1  0/235 (0.00%)  0 0/65 (0.00%)  0 1/65 (1.54%)  1
Nervous system disorders       
Headache * 1  1/235 (0.43%)  1 0/65 (0.00%)  0 0/65 (0.00%)  0
Presyncope * 1  0/235 (0.00%)  0 1/65 (1.54%)  1 0/65 (0.00%)  0
Grand mal convulsion * 1  0/235 (0.00%)  0 0/65 (0.00%)  0 1/65 (1.54%)  1
Surgical and medical procedures       
Thyroidectomy * 1  1/235 (0.43%)  1 0/65 (0.00%)  0 0/65 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
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 (3.83%)      6/65 (9.23%)      7/65 (10.77%)    
Gastrointestinal disorders       
Nausea * 1  2/235 (0.85%)  2 2/65 (3.08%)  2 0/65 (0.00%)  0
Infections and infestations       
Gastroenteritis viral * 1  1/235 (0.43%)  1 2/65 (3.08%)  3 0/65 (0.00%)  0
Sinusitis * 1  4/235 (1.70%)  4 1/65 (1.54%)  1 2/65 (3.08%)  2
Upper respiratory * 1  1/235 (0.43%)  1 1/65 (1.54%)  1 3/65 (4.62%)  3
Skin and subcutaneous tissue disorders       
Actinic keratosis * 1  1/235 (0.43%)  1 0/65 (0.00%)  0 2/65 (3.08%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Elizabeth M Nieman
Organization: Galderma Laboratories, L.P.
Phone: 817-961-5130
EMail: elizabeth.nieman@galderma.com
Layout table for additonal information
Responsible Party: Galderma Laboratories, L.P.
ClinicalTrials.gov Identifier: NCT01426269    
Other Study ID Numbers: US10183
First Submitted: August 26, 2011
First Posted: August 31, 2011
Results First Submitted: December 17, 2013
Results First Posted: August 4, 2014
Last Update Posted: August 4, 2014