Acne Vulgaris
Conditions
Keywords
acne vulgaris, inflammatory lesions
Brief summary
The primary objectives of the study is to show CD2475/101 40mg tablets taken once a day for 16 weeks is superior to the placebo in Change from baseline to Week 16(Last Observation Carry Forward, Intent To Treat) in inflammatory lesion counts.
Detailed description
Investigator's global assessment and lesion count will be performed at each study visit.
Interventions
DRUGCD2475/101 40 mg
Participants receive 40 mg of CD2475/101 tablets once a day for 16 weeks.
Participants receive 100 mg of Doxycycline capsule once a day for 16 weeks
DRUGPlacebo
Participants receive matching placebo tablet, matching placebo capsule once a day for 16 weeks.
Sponsors
Galderma R&D
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects 12 years of age or older * acne vulgaris with facial involvement * A score of 3 (Moderate) or 4 (Severe) on the Investigator's Global Assessment Scale (inflammatory) * 25 to 75 inflammatory lesions (papules and pustules) on the face (including the nose)
Exclusion criteria
* More than two acne nodules/cysts on the face * Acne conglobata, acne fulminans, secondary acne (chloracne, drug induced acne, etc.), or severe acne requiring systemic retinoid treatment * Underlying diseases or other dermatologic conditions that require the use of interfering topical or systemic therapy such as, but not limited to, atopic dermatitis, perioral dermatitis or rosacea * Beard or facial hair which might interfere with study assessments * planning excessive exposure to sun or ultraviolet light during the study (i.e. natural or artificial sunlight, including tanning booths and sun lamp) * Use of oral contraceptives solely for control of acne * Liver function test alanine transaminase (ALT) and/or aspartate transaminase (AST) 2.5 times above upper limit of normal * Renal function test serum creatinine at 150 umol/L (17 mg/L) or higher * Presence of oral or genital candidiasis or history of multiple episodes of oral or genital candidiasis * Females who intend to conceive a child within 5 months following Baseline visit * Males who intend to conceive a child with partner during the study period * Requiring concomitant use of methoxyflurane
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | From Baseline up to Week 16 (LOCF) | The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 0.5 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. Change from baseline in inflammatory lesion counts to Week 16 (LOCF) were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | From Baseline up to Week 16 (LOCF) | The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 0.5 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. Percent change from baseline in inflammatory lesion counts to Week 16 (LOCF) were reported. |
| Percent Change From Baseline in Total Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | From Baseline up to Week 16 (LOCF) | Total lesions were the sum of inflammatory lesion counts, non-inflammatory lesion counts, nodules and cysts. Percentage change from baseline in total lesion counts to Week 16 were reported. |
| Investigator Global Assessment (IGA) Success Rate at Week 16 (Last Observation Carried Forward [LOCF]) | Week 16 (LOCF) | IGA scale consisted of 5 grades (0-4) among which 0= Clear (no evidence of papules or pustules \[inflammatory lesions\]), 1= Almost clear (rare non-inflamed papules (papules must be resolving and hyperpigmented, though not pink-red), 2= Mild (few inflammatory lesions \[papules/pustules only; no nodulo-cystic lesions\]), 3=Moderate (multiple inflammatory lesions evident: many papules/pustules; up to two nodulocystic lesions), 4= Severe (inflammatory lesions are more apparent, many papules/pustules, few nodulo-cystic lesions). Success rate was defined as percentage of participants who achieved an Investigator Global Assessment (IGA) score of 1 (almost clear) or 0 (Clear) and at least a 2-grade improvement from Baseline to Week 16 (LOCF). |
| Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Baseline, Week 12, and Week 16 | Global assessments for inflammatory lesions of truncal acne were done separately on back and chest. The global assessments severity scale included 5 grades (0-4): where in 0= Clear-no evidence of papules or pustules (inflammatory lesions), 1= Almost clear- rare non-inflamed papules (papules must be resolving and may be hyperpigmented, though not pink-red), 2=Mild- few inflammatory lesions (papules/pustules only; no nodulo-cystic lesions), 3=Moderate- multiple inflammatory lesions evident: many papules/pustules; may be a few nodulocystic lesions, 4=Severe- inflammatory lesions are more apparent, many papules/pustules, may be a few nodulo-cystic lesions. |
| Number of Participants With at Least One Adverse Event (AE) | From Baseline up to Week 16 | An AE was any untoward medical occurrence in a participant or clinical investigation participants administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Number of participants with at least one AE were reported. |
| Change From Baseline in Non-Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | From Baseline up to Week 16 (LOCF) | The non-inflammatory lesion count was the count of open and closed comedones: Open comedone was a pigmented dilated pilosebaceous orifice (blackhead). Closed comedone was a tiny white papule (whitehead). Change from baseline in non-inflammatory lesion counts to week 16 were reported |
Countries
United States
Participant flow
Recruitment details
This study was conducted in United States between 29 March 2011 (first participant first visit) to 3 January 2012 (last participant last visit).
Pre-assignment details
A total of 662 participants randomized the study and dispensed with study drug out of which 487 completed study.
Participants by arm
| Arm | Count |
|---|---|
| CD2475/101 40 mg Participants received 40 mg of CD2475/101 oral tablet plus placebo capsule orally once daily for 16 weeks. | 216 |
| Doxycycline 100 mg Participants received 100 mg of Doxycycline capsule plus placebo tablet orally once daily for 16 weeks. | 224 |
| Placebo Participants received matching placebo tablet plus placebo capsule orally once daily for 16 weeks. | 222 |
| Total | 662 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 7 | 8 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 22 | 26 | 17 |
| Overall Study | Other | 2 | 3 | 1 |
| Overall Study | Protocol Violation | 3 | 5 | 3 |
| Overall Study | Withdrawal by Subject | 22 | 23 | 23 |
Baseline characteristics
| Characteristic | CD2475/101 40 mg | Doxycycline 100 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 123 Participants | 132 Participants | 133 Participants | 388 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 93 Participants | 92 Participants | 89 Participants | 274 Participants |
| Age, Continuous | 19.6 Years STANDARD_DEVIATION 7.7 | 19.6 Years STANDARD_DEVIATION 7.54 | 18.7 Years STANDARD_DEVIATION 6.34 | 19.3 Years STANDARD_DEVIATION 7.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 30 Participants | 37 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 181 Participants | 194 Participants | 185 Participants | 560 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 7 Participants | 7 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 49 Participants | 40 Participants | 136 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 5 Participants | 5 Participants | 16 Participants |
| Race (NIH/OMB) White | 159 Participants | 163 Participants | 170 Participants | 492 Participants |
| Region of Enrollment United States | 216 participants | 224 participants | 222 participants | 662 participants |
| Sex: Female, Male Female | 115 Participants | 121 Participants | 115 Participants | 351 Participants |
| Sex: Female, Male Male | 101 Participants | 103 Participants | 107 Participants | 311 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 216 | 0 / 223 | 0 / 222 |
| other Total, other adverse events | 29 / 216 | 51 / 223 | 29 / 222 |
| serious Total, serious adverse events | 1 / 216 | 4 / 223 | 2 / 222 |
Outcome results
Primary
Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF])
The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 0.5 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. Change from baseline in inflammatory lesion counts to Week 16 (LOCF) were reported.
Time frame: From Baseline up to Week 16 (LOCF)
Population: Intent To Treat (ITT) population consisted of all participants who were randomized and to whom study drug was dispensed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CD2475/101 40 mg | Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -16.1 lesion count | Standard Deviation 11.39 |
| Doxycycline 100 mg | Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -12.9 lesion count | Standard Deviation 14.6 |
| Placebo | Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -12.6 lesion count | Standard Deviation 16.44 |
p-value: 0.00695% CI: [-6.1, -1.1]ANCOVA
p-value: 0.02495% CI: [-5.4, -0.4]ANCOVA
p-value: 0.59595% CI: [-3.2, 1.8]ANCOVA
Secondary
Change From Baseline in Non-Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF])
The non-inflammatory lesion count was the count of open and closed comedones: Open comedone was a pigmented dilated pilosebaceous orifice (blackhead). Closed comedone was a tiny white papule (whitehead). Change from baseline in non-inflammatory lesion counts to week 16 were reported
Time frame: From Baseline up to Week 16 (LOCF)
Population: ITT population consisted of all participants who were randomized and to whom study drug was dispensed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CD2475/101 40 mg | Change From Baseline in Non-Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -10.0 lesion count | Standard Deviation 21.49 |
| Doxycycline 100 mg | Change From Baseline in Non-Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -5.2 lesion count | Standard Deviation 21.6 |
| Placebo | Change From Baseline in Non-Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -5.8 lesion count | Standard Deviation 18.19 |
Secondary
Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16
Global assessments for inflammatory lesions of truncal acne were done separately on back and chest. The global assessments severity scale included 5 grades (0-4): where in 0= Clear-no evidence of papules or pustules (inflammatory lesions), 1= Almost clear- rare non-inflamed papules (papules must be resolving and may be hyperpigmented, though not pink-red), 2=Mild- few inflammatory lesions (papules/pustules only; no nodulo-cystic lesions), 3=Moderate- multiple inflammatory lesions evident: many papules/pustules; may be a few nodulocystic lesions, 4=Severe- inflammatory lesions are more apparent, many papules/pustules, may be a few nodulo-cystic lesions.
Time frame: Baseline, Week 12, and Week 16
Population: ITT population consisted of all participants who were randomized and to whom study drug was dispensed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD2475/101 40 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Baseline : Lesion of Truncal Acne on Back | 1.6 Units on a scale | Standard Deviation 1.1 |
| CD2475/101 40 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Baseline : Lesion of Truncal Acne on Chest | 1.2 Units on a scale | Standard Deviation 1.04 |
| CD2475/101 40 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 12 : Lesions of Truncal Acne on Back | 1.2 Units on a scale | Standard Deviation 1.06 |
| CD2475/101 40 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 12 : Lesion of Truncal Acne on Chest | 0.9 Units on a scale | Standard Deviation 0.94 |
| CD2475/101 40 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 16 : Lesions of Truncal Acne on Back | 1.1 Units on a scale | Standard Deviation 1.06 |
| CD2475/101 40 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 16 : Lesion of Truncal Acne on Chest | 0.9 Units on a scale | Standard Deviation 1.01 |
| Doxycycline 100 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 16 : Lesion of Truncal Acne on Chest | 0.8 Units on a scale | Standard Deviation 0.93 |
| Doxycycline 100 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Baseline : Lesion of Truncal Acne on Back | 1.5 Units on a scale | Standard Deviation 1.09 |
| Doxycycline 100 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 12 : Lesion of Truncal Acne on Chest | 0.9 Units on a scale | Standard Deviation 0.99 |
| Doxycycline 100 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 16 : Lesions of Truncal Acne on Back | 1.0 Units on a scale | Standard Deviation 1.06 |
| Doxycycline 100 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Baseline : Lesion of Truncal Acne on Chest | 1.2 Units on a scale | Standard Deviation 1 |
| Doxycycline 100 mg | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 12 : Lesions of Truncal Acne on Back | 1.1 Units on a scale | Standard Deviation 1.05 |
| Placebo | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Baseline : Lesion of Truncal Acne on Chest | 1.1 Units on a scale | Standard Deviation 0.98 |
| Placebo | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 12 : Lesions of Truncal Acne on Back | 1.2 Units on a scale | Standard Deviation 1.04 |
| Placebo | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 16 : Lesion of Truncal Acne on Chest | 0.9 Units on a scale | Standard Deviation 0.95 |
| Placebo | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 12 : Lesion of Truncal Acne on Chest | 0.9 Units on a scale | Standard Deviation 0.95 |
| Placebo | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Baseline : Lesion of Truncal Acne on Back | 1.5 Units on a scale | Standard Deviation 1.07 |
| Placebo | Global Assessment for Inflammatory Lesions of Truncal Acne at Baseline, Week 12, and Week 16 | Week 16 : Lesions of Truncal Acne on Back | 1.2 Units on a scale | Standard Deviation 1.03 |
Secondary
Investigator Global Assessment (IGA) Success Rate at Week 16 (Last Observation Carried Forward [LOCF])
IGA scale consisted of 5 grades (0-4) among which 0= Clear (no evidence of papules or pustules \[inflammatory lesions\]), 1= Almost clear (rare non-inflamed papules (papules must be resolving and hyperpigmented, though not pink-red), 2= Mild (few inflammatory lesions \[papules/pustules only; no nodulo-cystic lesions\]), 3=Moderate (multiple inflammatory lesions evident: many papules/pustules; up to two nodulocystic lesions), 4= Severe (inflammatory lesions are more apparent, many papules/pustules, few nodulo-cystic lesions). Success rate was defined as percentage of participants who achieved an Investigator Global Assessment (IGA) score of 1 (almost clear) or 0 (Clear) and at least a 2-grade improvement from Baseline to Week 16 (LOCF).
Time frame: Week 16 (LOCF)
Population: ITT Population consisted of all participants who were randomized and to whom study drug was dispensed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CD2475/101 40 mg | Investigator Global Assessment (IGA) Success Rate at Week 16 (Last Observation Carried Forward [LOCF]) | 14.4 Percentage of participants |
| Doxycycline 100 mg | Investigator Global Assessment (IGA) Success Rate at Week 16 (Last Observation Carried Forward [LOCF]) | 13.8 Percentage of participants |
| Placebo | Investigator Global Assessment (IGA) Success Rate at Week 16 (Last Observation Carried Forward [LOCF]) | 7.7 Percentage of participants |
Secondary
Number of Participants With at Least One Adverse Event (AE)
An AE was any untoward medical occurrence in a participant or clinical investigation participants administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Number of participants with at least one AE were reported.
Time frame: From Baseline up to Week 16
Population: Safety Population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CD2475/101 40 mg | Number of Participants With at Least One Adverse Event (AE) | 63 Participants |
| Doxycycline 100 mg | Number of Participants With at Least One Adverse Event (AE) | 83 Participants |
| Placebo | Number of Participants With at Least One Adverse Event (AE) | 89 Participants |
Secondary
Percent Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF])
The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 0.5 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. Percent change from baseline in inflammatory lesion counts to Week 16 (LOCF) were reported.
Time frame: From Baseline up to Week 16 (LOCF)
Population: ITT population consisted of all participants who were randomized and to whom study drug was dispensed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CD2475/101 40 mg | Percent Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -48.6 percent change | Standard Deviation 31.72 |
| Doxycycline 100 mg | Percent Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -40.3 percent change | Standard Deviation 40.9 |
| Placebo | Percent Change From Baseline in Inflammatory Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -37.1 percent change | Standard Deviation 44.45 |
Secondary
Percent Change From Baseline in Total Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF])
Total lesions were the sum of inflammatory lesion counts, non-inflammatory lesion counts, nodules and cysts. Percentage change from baseline in total lesion counts to Week 16 were reported.
Time frame: From Baseline up to Week 16 (LOCF)
Population: ITT population consisted of all participants who were randomized and to whom study drug was dispensed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CD2475/101 40 mg | Percent Change From Baseline in Total Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -38.3 percent change | Standard Deviation 32.24 |
| Doxycycline 100 mg | Percent Change From Baseline in Total Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -27.8 percent change | Standard Deviation 43.94 |
| Placebo | Percent Change From Baseline in Total Lesion Counts to Week 16 (Last Observation Carried Forward [LOCF]) | -27.8 percent change | Standard Deviation 38.05 |