Acne Vulgaris
Conditions
Brief summary
Randomized, multi-center, double-blind, placebo-controlled 12-week study to assess the safety and efficacy of 3 doses of an oral formulation of Doxycycline oral tablets using the Investigator's Global Assessment (IGA) score and the absolute change from baseline in inflammatory lesion count in patients with moderate to severe facial acne vulgaris. Additionally, the absolute change from baseline in non-inflammatory and total lesions of the active study medication to placebo will be evaluated.
Interventions
DRUGDoxycycline 0.6 mg/kg/day
doxycycline 40 mg/day, oral, 12 weeks
DRUGDoxycycline 1.2 mg/kg/day
doxycycline 80 mg/day, 12 weeks
DRUGDoxycycline 2.4 mg/kg/day
doxycycline 160 mg/day, 12 weeks
DRUGPlacebo
Placebo, 12 weeks
Sponsors
Warner Chilcott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Must be between 12 and 45 years of age. * Has a diagnosis of moderate to severe facial acne vulgaris with no more than two nodules on the face
Exclusion criteria
* Is allergic to tetracycline-class antibiotics or to any ingredient in the study medication. * Has a history of pseudomembranous colitis or antibiotic-associated colitis. * Has a history of hepatitis or liver damage or renal impairment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Patients With Successful Outcome Investigator's Global Assessment (IGA) Score at Week 12, Intent to Treat (ITT) Population | Week 12 | IGA: 0/clear (clear skin no lesions, inflammatory or non-inflammatory), 1/almost clear (rare non-inflammatory lesion w/no more than 1 small inflammatory lesion), 2/mild (some non-inflammatory lesions with no more than a few inflammatory lesions, papules/pustules only, no nodular lesions), 3/moderate (up to many non-inflammatory lesions, some inflammatory lesions, no more than 1 small nodular lesion), 4/severe (many non-inflammatory & inflammatory lesions, no more than a few nodular lesions. Lower score improvement in score. Success=IGA decrease of at least 2 grades from baseline score. |
| Absolute Change in Inflammatory Lesion Count From Baseline to Week 12, ITT Population | Baseline to Week 12 | Change derived as Baseline evaluation minus the Week 12 evaluation. Thus a positive change reflects a reduction in lesion count. Inflammatory Lesion Count includes nodules, papules and pustules. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline to Week 12 in NonInflammatory Lesion Count, ITT Population | Baseline to Week 12 | Noninflammatory Lesion Count includes open and closed comedones. |
| Absolute Change From Baseline to Week 12 in Total Lesion Count, ITT Population | Baseline to Week 12 | Total Lesion Count is the sum of inflammatory and noninflammatory lesions. |
Countries
United States
Participant flow
Recruitment details
Recruitment began 4 Mar '08
Participants by arm
| Arm | Count |
|---|---|
| Doxycycline 0.6 mg/kg/Day 40 mg doxycycline tablet plus 2 placebo tablets daily | 64 |
| Doxycycline 1.2 mg/kg/Day 80 mg doxycycline (1-80 mg tablet) plus 2 placebo tablets daily | 65 |
| Doxycycline 2.4 mg/kg/Day 160 mg doxycyline (2-80 mg tablets) plus 1 placebo tablet daily | 61 |
| Placebo Comparator 3 placebo tablets daily matching active 40 & 80 mg tablets | 67 |
| Total | 257 |
Baseline characteristics
| Characteristic | Doxycycline 0.6 mg/kg/Day | Doxycycline 1.2 mg/kg/Day | Doxycycline 2.4 mg/kg/Day | Placebo Comparator | Total |
|---|---|---|---|---|---|
| Age Continuous | 19.3 years STANDARD_DEVIATION 5.2 | 19.4 years STANDARD_DEVIATION 6.6 | 20.7 years STANDARD_DEVIATION 7.4 | 20.2 years STANDARD_DEVIATION 7.5 | 19.9 years STANDARD_DEVIATION 6.7 |
| Age, Customized < 18 years | 32 Participants | 26 Participants | 34 Participants | 32 Participants | 124 Participants |
| Age, Customized >= 18 years | 32 Participants | 39 Participants | 27 Participants | 35 Participants | 133 Participants |
| Region of Enrollment United States | 64 participants | 65 participants | 61 participants | 67 participants | 257 participants |
| Sex: Female, Male Female | 35 Participants | 30 Participants | 36 Participants | 35 Participants | 136 Participants |
| Sex: Female, Male Male | 29 Participants | 35 Participants | 25 Participants | 32 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 64 | 20 / 65 | 29 / 61 | 25 / 67 |
| serious Total, serious adverse events | 0 / 64 | 0 / 65 | 0 / 61 | 1 / 67 |
Outcome results
Primary
Absolute Change in Inflammatory Lesion Count From Baseline to Week 12, ITT Population
Change derived as Baseline evaluation minus the Week 12 evaluation. Thus a positive change reflects a reduction in lesion count. Inflammatory Lesion Count includes nodules, papules and pustules.
Time frame: Baseline to Week 12
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline 0.6 mg/kg/Day | Absolute Change in Inflammatory Lesion Count From Baseline to Week 12, ITT Population | 8.1 Lesions | Standard Deviation 13.2 |
| Doxycycline 1.2 mg/kg/Day | Absolute Change in Inflammatory Lesion Count From Baseline to Week 12, ITT Population | 11.5 Lesions | Standard Deviation 12.1 |
| Doxycycline 2.4 mg/kg/Day | Absolute Change in Inflammatory Lesion Count From Baseline to Week 12, ITT Population | 14.0 Lesions | Standard Deviation 19.7 |
| Placebo Comparator | Absolute Change in Inflammatory Lesion Count From Baseline to Week 12, ITT Population | 7.3 Lesions | Standard Deviation 13.8 |
p-value: 0.807Cochran-Mantel-Haenszel
p-value: 0.075Cochran-Mantel-Haenszel
p-value: 0.039Cochran-Mantel-Haenszel
Primary
Percentage Patients With Successful Outcome Investigator's Global Assessment (IGA) Score at Week 12, Intent to Treat (ITT) Population
IGA: 0/clear (clear skin no lesions, inflammatory or non-inflammatory), 1/almost clear (rare non-inflammatory lesion w/no more than 1 small inflammatory lesion), 2/mild (some non-inflammatory lesions with no more than a few inflammatory lesions, papules/pustules only, no nodular lesions), 3/moderate (up to many non-inflammatory lesions, some inflammatory lesions, no more than 1 small nodular lesion), 4/severe (many non-inflammatory & inflammatory lesions, no more than a few nodular lesions. Lower score improvement in score. Success=IGA decrease of at least 2 grades from baseline score.
Time frame: Week 12
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline 0.6 mg/kg/Day | Percentage Patients With Successful Outcome Investigator's Global Assessment (IGA) Score at Week 12, Intent to Treat (ITT) Population | 14.1 Percentage of Participants |
| Doxycycline 1.2 mg/kg/Day | Percentage Patients With Successful Outcome Investigator's Global Assessment (IGA) Score at Week 12, Intent to Treat (ITT) Population | 15.4 Percentage of Participants |
| Doxycycline 2.4 mg/kg/Day | Percentage Patients With Successful Outcome Investigator's Global Assessment (IGA) Score at Week 12, Intent to Treat (ITT) Population | 29.5 Percentage of Participants |
| Placebo Comparator | Percentage Patients With Successful Outcome Investigator's Global Assessment (IGA) Score at Week 12, Intent to Treat (ITT) Population | 16.4 Percentage of Participants |
p-value: 0.77995% CI: [-14.8, 10.3]Cochran-Mantel-Haenszel
p-value: 0.98395% CI: [-13.7, 11.7]Cochran-Mantel-Haenszel
p-value: 0.08795% CI: [-1.5, 27.3]Cochran-Mantel-Haenszel
Secondary
Absolute Change From Baseline to Week 12 in NonInflammatory Lesion Count, ITT Population
Noninflammatory Lesion Count includes open and closed comedones.
Time frame: Baseline to Week 12
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline 0.6 mg/kg/Day | Absolute Change From Baseline to Week 12 in NonInflammatory Lesion Count, ITT Population | 8.5 Lesions | Standard Deviation 19.1 |
| Doxycycline 1.2 mg/kg/Day | Absolute Change From Baseline to Week 12 in NonInflammatory Lesion Count, ITT Population | 5.2 Lesions | Standard Deviation 28.1 |
| Doxycycline 2.4 mg/kg/Day | Absolute Change From Baseline to Week 12 in NonInflammatory Lesion Count, ITT Population | 6.5 Lesions | Standard Deviation 16.2 |
| Placebo Comparator | Absolute Change From Baseline to Week 12 in NonInflammatory Lesion Count, ITT Population | 1.8 Lesions | Standard Deviation 31 |
p-value: 0.212Cochran-Mantel-Haenszel
p-value: 0.505Cochran-Mantel-Haenszel
p-value: 0.399Cochran-Mantel-Haenszel
Secondary
Absolute Change From Baseline to Week 12 in Total Lesion Count, ITT Population
Total Lesion Count is the sum of inflammatory and noninflammatory lesions.
Time frame: Baseline to Week 12
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline 0.6 mg/kg/Day | Absolute Change From Baseline to Week 12 in Total Lesion Count, ITT Population | 16.6 Lesions | Standard Deviation 25.6 |
| Doxycycline 1.2 mg/kg/Day | Absolute Change From Baseline to Week 12 in Total Lesion Count, ITT Population | 16.8 Lesions | Standard Deviation 32.7 |
| Doxycycline 2.4 mg/kg/Day | Absolute Change From Baseline to Week 12 in Total Lesion Count, ITT Population | 20.5 Lesions | Standard Deviation 25 |
| Placebo Comparator | Absolute Change From Baseline to Week 12 in Total Lesion Count, ITT Population | 9.1 Lesions | Standard Deviation 38.1 |
p-value: 0.276Cochran-Mantel-Haenszel
p-value: 0.231Cochran-Mantel-Haenszel
p-value: 0.081Cochran-Mantel-Haenszel