Atopic Dermatitis
Conditions
Brief summary
The study will assess the safety, pharmacokinetics (PK), and efficacy of different doses of roflumilast (ARQ-151) cream (0.05% and 0.15%) vs placebo applied once daily (QD) for 28 days by adolescents and adults with atopic dermatitis.
Detailed description
This is a parallel group, double blind, vehicle-controlled study in which roflumilast cream 0.05% or 0.15% or vehicle is applied QD x 28 days to adolescent and adult subjects with atopic dermatitis. A subset of subjects will have serial PK testing, which will include the first few adolescents and adults enrolled in the study.
Interventions
Roflumilast 0.05% cream for topical application
Roflumilast 0.15% cream for topical application
DRUGVehicle Cream
Inactive vehicle cream matched to roflumilast cream for topical application.
Sponsors
Arcutis Biotherapeutics, Inc.
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
1. Participants legally competent to sign and give informed consent or, in the case of adolescents, assent with consent of a parent(s) or legal guardian, as required by local laws. 2. Males and females ages 12 years and older (inclusive) at the time of consent. 3. Clinical diagnosis of active atopic dermatitis for at least 6 months. 4. BSA (Body Surface Area) involvement of at least 2% but no more than 25% at Baseline. 5. vIGA-AD (validated Investigator Global Assessment-Atopic Dermatitis) score of 'mild' ('2') or 'moderate ('3') at Baseline. 6. EASI (Eczema Area and Severity Index) score of ≥ 5 at Baseline. 7. Females of childbearing potential must have a negative serum pregnancy test at Screening and, if sexually active, agree to use birth control throughout the trial. 8. In good health as judged by the Investigator, based on medical history, physical examination, and clinical tests.
Exclusion criteria
1. Subjects with any serious medical condition or clinically significant physical examination or test abnormality that would prevent study participation or place the subject at significant risk. 2. Evidence of skin conditions other than AD (atopic dermatitis) that would interfere with evaluation of the effect of the study medication. 3. Pregnant or lactating women or women planning to become pregnant during the study. 4. Known allergies to excipients in ARQ-151 cream. 5. Subjects who cannot discontinue the use of strong P-450 cytochrome inducers or inhibitors . 6. Subjects who are unwilling to refrain from using a tanning bed as well as outdoor tanning or excessive sun exposure. 7. Subjects with unstable AD or who cannot discontinue systemic and/or topical therapies for the treatment of AD. 8. Known or suspected: * severe renal insufficiency or moderate to severe hepatic disorders (Child-Pugh B or C) * history of chronic infectious disease (e.g., hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)) * within last 5 years, a history of severe depression, suicidal ideation 9. Previous treatment with ARQ-151. 10. Subjects with a history of chronic alcohol or drug abuse in past 6 months. 11. Current or a history of cancer within 5 years with the exception of fully excised skin basal cell carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix. 12. Subjects with active infection that requires oral or intravenous administration of antibiotics, antifungal or antiviral agents. 13. Subjects with a history of a major surgery within 8 weeks prior to Baseline or has a major surgery planned during the study. 14. Subjects with any condition which makes them unsuitable for clinical study participation or are family members of the clinical study site, clinical study staff, sponsor, or family members of enrolled subjects.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4 | Baseline and Week 4 | The least squares (LS) mean (SD) change from baseline in EASI Total Score at Week 4 is reported. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in EASI Total Score at Weeks 1 and 2 | Baseline and Weeks 1 and 2 | The LS mean (SD) change from baseline in EASI Total Score at Weeks 1 and 2 is reported. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. |
| Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | Baseline and Weeks 1, 2, and 4 | The number of participants with a decrease of at least 50% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. |
| Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | Baseline and Weeks 1, 2, and 4 | The number of participants with a decrease of at least 75% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. |
| Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | Baseline and Weeks 1, 2, and 4 | The number of participants with a decrease of at least 90% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. In some instances, it was not possible to compare roflumilast to vehicle due to low number of cases. |
| Percentage Change From Baseline in EASI Total Score | Baseline and Weeks 1, 2, and 4 | The LS mean (SD) percentage change from baseline in EASI Total Score at Weeks 1, 2, and 4 is reported. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. |
| Mean Change From Baseline in Body Surface Area (BSA) Involvement | Baseline and Weeks 1, 2, and 4 | The LS mean (SE) change from baseline in BSA involvement at Weeks 1, 2, and 4 is presented. The BSA affected by AD was determined by the subject's hand method, where the subject's hand (including fingers) surface area was assumed to equal 1% of BSA. Negative scores indicate improvement of symptoms, whereas positive scores indicate worsening. |
| Worse Itch Numerical Rating Score (WI-NRS) Score Change | Baseline and Weeks 1, 2, and 4 | The LS mean (SE) change from baseline in WI-NRS score is presented. The WI-NRS is a simple, single item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 (no itch) to 10 (worst imaginable itch) the subject experienced in the previous 24 hours. Higher scores indicate greater symptom severity. |
| Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | Baseline and Weeks 1, 2, and 4 | The number of participants achieving a ≥4-point improvement from Baseline in WI-NRS score is presented. The WI-NRS is a simple, single item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 (no itch) to 10 (worst imaginable itch) the subject experienced in the previous 24 hours. Higher scores indicate greater symptom severity. |
| Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | Baseline and Weeks 1, 2, and 4 | The number of participants with a decrease of 100% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. In some instances, it was not possible to compare roflumilast to vehicle due to low number of cases. |
Countries
Canada, United States
Participant flow
Recruitment details
Adolescent (12 to 17 years of age) and adult (≥18 years of age) male and female participants with mild to moderate atopic dermatitis (AD) were enrolled at 3 study sites in Canada and 19 sites in the US.
Participants by arm
| Arm | Count |
|---|---|
| Roflumilast Cream 0.05% Participants apply roflumilast cream 0.05% QD for 28 days.
Roflumilast Cream 0.05%: Roflumilast 0.05% cream for topical application | 46 |
| Roflumilast Cream 0.15% Participants apply roflumilast cream 0.15% QD for 28 days.
Roflumilast Cream 0.15%: Roflumilast 0.15% cream for topical application | 45 |
| Vehicle Cream Participants apply vehicle cream QD for 28 days.
Vehicle Cream: Inactive vehicle cream matched to roflumilast cream for topical application. | 45 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 1 |
| Overall Study | Worsening of AD | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Roflumilast Cream 0.05% | Total | Vehicle Cream | Roflumilast Cream 0.15% |
|---|---|---|---|---|
| Age, Continuous | 44.3 years STANDARD_DEVIATION 16.98 | 41.6 years STANDARD_DEVIATION 17.11 | 42.4 years STANDARD_DEVIATION 17.64 | 38.0 years STANDARD_DEVIATION 16.46 |
| Baseline Body Surface Area (BSA) Score | 8.4 percentage of body surface area STANDARD_DEVIATION 7.11 | 9.5 percentage of body surface area STANDARD_DEVIATION 6.6 | 10.5 percentage of body surface area STANDARD_DEVIATION 6.62 | 9.6 percentage of body surface area STANDARD_DEVIATION 5.99 |
| Baseline Eczema Area and Severity Index (EASI) Score | 8.44 score on a scale STANDARD_DEVIATION 4.149 | 9.04 score on a scale STANDARD_DEVIATION 4.039 | 9.20 score on a scale STANDARD_DEVIATION 3.877 | 9.50 score on a scale STANDARD_DEVIATION 4.097 |
| Baseline Worst Itch Numerical Rating Scale (WI-NRS) Score | 6.48 score on a scale STANDARD_DEVIATION 1.986 | 6.76 score on a scale STANDARD_DEVIATION 2.057 | 7.20 score on a scale STANDARD_DEVIATION 2.106 | 6.60 score on a scale STANDARD_DEVIATION 2.049 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 32 Participants | 13 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 103 Participants | 32 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 8 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 36 Participants | 11 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 2 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 88 Participants | 32 Participants | 24 Participants |
| Sex: Female, Male Female | 31 Participants | 93 Participants | 29 Participants | 33 Participants |
| Sex: Female, Male Male | 15 Participants | 43 Participants | 16 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 45 | 0 / 45 |
| other Total, other adverse events | 0 / 46 | 0 / 45 | 0 / 45 |
| serious Total, serious adverse events | 1 / 46 | 0 / 45 | 0 / 45 |
Outcome results
Primary
Mean Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4
The least squares (LS) mean (SD) change from baseline in EASI Total Score at Week 4 is reported. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI.
Time frame: Baseline and Week 4
Population: All randomized participants with data are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast Cream 0.05% | Mean Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4 | -6.03 score on a scale | Standard Deviation 0.503 |
| Roflumilast Cream 0.15% | Mean Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4 | -6.44 score on a scale | Standard Deviation 0.492 |
| Vehicle Cream | Mean Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4 | -4.84 score on a scale | Standard Deviation 0.492 |
Comparison: Change from Baseline in Week 4 EASI Total Score: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.35695% CI: [-2.983, 0.619]MMRM
Comparison: Change from Baseline in Week 4 EASI Total Score: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.09795% CI: [-3.382, 0.178]MMRM
Secondary
Mean Change From Baseline in Body Surface Area (BSA) Involvement
The LS mean (SE) change from baseline in BSA involvement at Weeks 1, 2, and 4 is presented. The BSA affected by AD was determined by the subject's hand method, where the subject's hand (including fingers) surface area was assumed to equal 1% of BSA. Negative scores indicate improvement of symptoms, whereas positive scores indicate worsening.
Time frame: Baseline and Weeks 1, 2, and 4
Population: All randomized participants with data are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Roflumilast Cream 0.05% | Mean Change From Baseline in Body Surface Area (BSA) Involvement | Week 2 | -2.69 percentage of BSA affected | Standard Error 0.58 |
| Roflumilast Cream 0.05% | Mean Change From Baseline in Body Surface Area (BSA) Involvement | Week 1 | -1.19 percentage of BSA affected | Standard Error 0.407 |
| Roflumilast Cream 0.05% | Mean Change From Baseline in Body Surface Area (BSA) Involvement | Week 4 | -4.41 percentage of BSA affected | Standard Error 0.658 |
| Roflumilast Cream 0.15% | Mean Change From Baseline in Body Surface Area (BSA) Involvement | Week 2 | -3.63 percentage of BSA affected | Standard Error 0.57 |
| Roflumilast Cream 0.15% | Mean Change From Baseline in Body Surface Area (BSA) Involvement | Week 1 | -1.67 percentage of BSA affected | Standard Error 0.407 |
| Roflumilast Cream 0.15% | Mean Change From Baseline in Body Surface Area (BSA) Involvement | Week 4 | -5.10 percentage of BSA affected | Standard Error 0.645 |
| Vehicle Cream | Mean Change From Baseline in Body Surface Area (BSA) Involvement | Week 1 | -1.57 percentage of BSA affected | Standard Error 0.405 |
| Vehicle Cream | Mean Change From Baseline in Body Surface Area (BSA) Involvement | Week 4 | -4.16 percentage of BSA affected | Standard Error 0.644 |
| Vehicle Cream | Mean Change From Baseline in Body Surface Area (BSA) Involvement | Week 2 | -3.29 percentage of BSA affected | Standard Error 0.568 |
Comparison: Change from Baseline in BSA Affected at Week 1: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.98995% CI: [-1.098, 1.852]MMRM
Comparison: Change from Baseline in BSA Affected at Week 1: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: >0.99995% CI: [-1.566, 1.367]MMRM
Comparison: Change from Baseline in BSA Affected at Week 2: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.96695% CI: [-1.51, 2.702]MMRM
Comparison: Change from Baseline in BSA Affected at Week 2: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.99995% CI: [-2.415, 1.744]MMRM
Comparison: Change from Baseline in BSA Affected at Week 4: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: >0.99995% CI: [-2.624, 2.119]MMRM
Comparison: Change from Baseline in BSA Affected at Week 4: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.79895% CI: [-3.285, 1.398]MMRM
Secondary
Mean Change From Baseline in EASI Total Score at Weeks 1 and 2
The LS mean (SD) change from baseline in EASI Total Score at Weeks 1 and 2 is reported. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI.
Time frame: Baseline and Weeks 1 and 2
Population: All randomized participants with data are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Roflumilast Cream 0.05% | Mean Change From Baseline in EASI Total Score at Weeks 1 and 2 | Week 1 | -3.11 score on a scale | Standard Deviation 0.416 |
| Roflumilast Cream 0.05% | Mean Change From Baseline in EASI Total Score at Weeks 1 and 2 | Week 2 | -4.80 score on a scale | Standard Deviation 0.479 |
| Roflumilast Cream 0.15% | Mean Change From Baseline in EASI Total Score at Weeks 1 and 2 | Week 1 | -2.77 score on a scale | Standard Deviation 0.57 |
| Roflumilast Cream 0.15% | Mean Change From Baseline in EASI Total Score at Weeks 1 and 2 | Week 2 | -5.02 score on a scale | Standard Deviation 0.469 |
| Vehicle Cream | Mean Change From Baseline in EASI Total Score at Weeks 1 and 2 | Week 1 | -2.19 score on a scale | Standard Deviation 0.414 |
| Vehicle Cream | Mean Change From Baseline in EASI Total Score at Weeks 1 and 2 | Week 2 | -4.31 score on a scale | Standard Deviation 0.47 |
Comparison: Change from Baseline in Week 1 EASI Total Score: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.4495% CI: [-2.412, 0.568]MMRM
Comparison: Change from Baseline in Week 1 EASI Total Score: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.87595% CI: [-2.061, 0.914]MMRM
Secondary
Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score
The number of participants achieving a ≥4-point improvement from Baseline in WI-NRS score is presented. The WI-NRS is a simple, single item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 (no itch) to 10 (worst imaginable itch) the subject experienced in the previous 24 hours. Higher scores indicate greater symptom severity.
Time frame: Baseline and Weeks 1, 2, and 4
Population: All randomized participants with data are included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roflumilast Cream 0.05% | Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | Week 2 | 10 Participants |
| Roflumilast Cream 0.05% | Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | Week 1 | 11 Participants |
| Roflumilast Cream 0.05% | Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | Week 4 | 21 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | Week 2 | 15 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | Week 1 | 15 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | Week 4 | 17 Participants |
| Vehicle Cream | Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | Week 1 | 9 Participants |
| Vehicle Cream | Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | Week 4 | 18 Participants |
| Vehicle Cream | Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | Week 2 | 16 Participants |
Comparison: Number of Participants Achieving a ≥4-Point Improvement from Baseline WI-NRS at Week 1: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.637Cochran-Mantel-Haenszel
Comparison: Number of Participants Achieving a ≥4-Point Improvement from Baseline WI-NRS at Week 1: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.124Cochran-Mantel-Haenszel
Comparison: Number of Participants Achieving a ≥4-Point Improvement from Baseline WI-NRS at Week 2: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.196Cochran-Mantel-Haenszel
Comparison: Number of Participants Achieving a ≥4-Point Improvement from Baseline WI-NRS at Week 2: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.985Cochran-Mantel-Haenszel
Comparison: Number of Participants Achieving a ≥4-Point Improvement from Baseline WI-NRS at Week 4: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.401Cochran-Mantel-Haenszel
Comparison: Number of Participants Achieving a ≥4-Point Improvement from Baseline WI-NRS at Week 4: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.996Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100)
The number of participants with a decrease of 100% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. In some instances, it was not possible to compare roflumilast to vehicle due to low number of cases.
Time frame: Baseline and Weeks 1, 2, and 4
Population: All randomized participants with ≥1 post-baseline assessment are included (LOCF used for missing data after Week 1).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roflumilast Cream 0.05% | Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | Week 2 | 1 Participants |
| Roflumilast Cream 0.05% | Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | Week 1 | 0 Participants |
| Roflumilast Cream 0.05% | Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | Week 4 | 1 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | Week 2 | 2 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | Week 1 | 0 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | Week 4 | 5 Participants |
| Vehicle Cream | Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | Week 1 | 0 Participants |
| Vehicle Cream | Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | Week 4 | 1 Participants |
| Vehicle Cream | Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | Week 2 | 0 Participants |
Comparison: Number Achieving EASI-100 at Week 2: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.34Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-100 at Week 2: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.146Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-100 at Week 4: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.967Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-100 at Week 4: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.088Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50)
The number of participants with a decrease of at least 50% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI.
Time frame: Baseline and Weeks 1, 2, and 4
Population: All randomized participants with ≥1 post-baseline assessment are included (last observation carried forward \[LOCF\] used for missing data after Week 1).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roflumilast Cream 0.05% | Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | Week 2 | 27 Participants |
| Roflumilast Cream 0.05% | Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | Week 1 | 14 Participants |
| Roflumilast Cream 0.05% | Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | Week 4 | 32 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | Week 2 | 23 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | Week 1 | 11 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | Week 4 | 33 Participants |
| Vehicle Cream | Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | Week 1 | 10 Participants |
| Vehicle Cream | Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | Week 4 | 25 Participants |
| Vehicle Cream | Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | Week 2 | 22 Participants |
Comparison: Number Achieving EASI-50 at Week 1: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.352Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-50 at Week 1: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.803Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-50 at Week 2: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.25Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-50 at Week 2: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.756Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-50 at Week 4: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.097Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-50 at Week 4: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.054Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75)
The number of participants with a decrease of at least 75% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI.
Time frame: Baseline and Weeks 1, 2, and 4
Population: All randomized participants with ≥1 post-baseline assessment are included (LOCF used for missing data after Week 1).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roflumilast Cream 0.05% | Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | Week 2 | 8 Participants |
| Roflumilast Cream 0.05% | Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | Week 1 | 4 Participants |
| Roflumilast Cream 0.05% | Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | Week 4 | 26 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | Week 2 | 14 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | Week 1 | 6 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | Week 4 | 23 Participants |
| Vehicle Cream | Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | Week 1 | 1 Participants |
| Vehicle Cream | Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | Week 4 | 14 Participants |
| Vehicle Cream | Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | Week 2 | 11 Participants |
Comparison: Number Achieving EASI-75 at Week 1: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.178Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-75 at Week 1: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.046Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-75 at Week 2: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.469Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-75 at Week 2: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.446Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-75 at Week 4: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.009Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-75 at Week 4: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.045Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90)
The number of participants with a decrease of at least 90% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. In some instances, it was not possible to compare roflumilast to vehicle due to low number of cases.
Time frame: Baseline and Weeks 1, 2, and 4
Population: All randomized participants with ≥1 post-baseline assessment are included (LOCF used for missing data after Week 1).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roflumilast Cream 0.05% | Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | Week 2 | 1 Participants |
| Roflumilast Cream 0.05% | Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | Week 1 | 0 Participants |
| Roflumilast Cream 0.05% | Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | Week 4 | 8 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | Week 2 | 6 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | Week 1 | 1 Participants |
| Roflumilast Cream 0.15% | Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | Week 4 | 12 Participants |
| Vehicle Cream | Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | Week 1 | 0 Participants |
| Vehicle Cream | Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | Week 4 | 8 Participants |
| Vehicle Cream | Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | Week 2 | 4 Participants |
Comparison: Number Achieving EASI-90 at Week 1: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.317Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-90 at Week 2: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.182Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-90 at Week 2: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.485Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-90 at Week 4: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.913Cochran-Mantel-Haenszel
Comparison: Number Achieving EASI-90 at Week 4: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.288Cochran-Mantel-Haenszel
Secondary
Percentage Change From Baseline in EASI Total Score
The LS mean (SD) percentage change from baseline in EASI Total Score at Weeks 1, 2, and 4 is reported. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI.
Time frame: Baseline and Weeks 1, 2, and 4
Population: All randomized participants with data are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Roflumilast Cream 0.05% | Percentage Change From Baseline in EASI Total Score | Week 2 | -54.30 percent change | Standard Deviation 4.663 |
| Roflumilast Cream 0.05% | Percentage Change From Baseline in EASI Total Score | Week 1 | -35.77 percent change | Standard Deviation 4.297 |
| Roflumilast Cream 0.05% | Percentage Change From Baseline in EASI Total Score | Week 4 | -69.37 percent change | Standard Deviation 4.643 |
| Roflumilast Cream 0.15% | Percentage Change From Baseline in EASI Total Score | Week 2 | -57.65 percent change | Standard Deviation 4.567 |
| Roflumilast Cream 0.15% | Percentage Change From Baseline in EASI Total Score | Week 1 | -34.67 percent change | Standard Deviation 4.273 |
| Roflumilast Cream 0.15% | Percentage Change From Baseline in EASI Total Score | Week 4 | -72.32 percent change | Standard Deviation 4.546 |
| Vehicle Cream | Percentage Change From Baseline in EASI Total Score | Week 1 | -24.39 percent change | Standard Deviation 4.279 |
| Vehicle Cream | Percentage Change From Baseline in EASI Total Score | Week 4 | -55.84 percent change | Standard Deviation 4.551 |
| Vehicle Cream | Percentage Change From Baseline in EASI Total Score | Week 2 | -48.48 percent change | Standard Deviation 4.571 |
Comparison: Percent Change from Baseline in Week 2 EASI Total Score: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.912-22.52% CI: [-22.52, 10.88]MMRM
Comparison: Percent Change from Baseline in Week 2 EASI Total Score: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.54895% CI: [-25.686, 7.341]MMRM
Comparison: Percent Change from Baseline in Week 1 EASI Total Score: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.24895% CI: [-26.789, 4.044]MMRM
Comparison: Percent Change from Baseline in Week 1 EASI Total Score: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.34995% CI: [-25.666, 5.114]MMRM
Comparison: Percent Change from Baseline in Week 4 EASI Total Score: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.16495% CI: [-30.157, 3.097]MMRM
Comparison: Percent Change from Baseline in Week 4 EASI Total Score: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.04995% CI: [-32.921, -0.048]MMRM
Secondary
Worse Itch Numerical Rating Score (WI-NRS) Score Change
The LS mean (SE) change from baseline in WI-NRS score is presented. The WI-NRS is a simple, single item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 (no itch) to 10 (worst imaginable itch) the subject experienced in the previous 24 hours. Higher scores indicate greater symptom severity.
Time frame: Baseline and Weeks 1, 2, and 4
Population: All randomized participants with data are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Roflumilast Cream 0.05% | Worse Itch Numerical Rating Score (WI-NRS) Score Change | Week 2 | -2.46 score on a scale | Standard Error 0.415 |
| Roflumilast Cream 0.05% | Worse Itch Numerical Rating Score (WI-NRS) Score Change | Week 1 | -2.21 score on a scale | Standard Error 2.13 |
| Roflumilast Cream 0.05% | Worse Itch Numerical Rating Score (WI-NRS) Score Change | Week 4 | -3.34 score on a scale | Standard Error 0.449 |
| Roflumilast Cream 0.15% | Worse Itch Numerical Rating Score (WI-NRS) Score Change | Week 2 | -2.76 score on a scale | Standard Error 0.413 |
| Roflumilast Cream 0.15% | Worse Itch Numerical Rating Score (WI-NRS) Score Change | Week 1 | -2.46 score on a scale | Standard Error 0.361 |
| Roflumilast Cream 0.15% | Worse Itch Numerical Rating Score (WI-NRS) Score Change | Week 4 | -3.23 score on a scale | Standard Error 0.444 |
| Vehicle Cream | Worse Itch Numerical Rating Score (WI-NRS) Score Change | Week 1 | -1.7 score on a scale | Standard Error 2.52 |
| Vehicle Cream | Worse Itch Numerical Rating Score (WI-NRS) Score Change | Week 4 | -2.73 score on a scale | Standard Error 0.44 |
| Vehicle Cream | Worse Itch Numerical Rating Score (WI-NRS) Score Change | Week 2 | -2.04 score on a scale | Standard Error 0.408 |
Comparison: Change from Baseline in WI-NRS at Week 1: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.46695% CI: [-2.075, 0.506]MMRM
Comparison: Change from Baseline in WI-NRS at Week 1: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.1895% CI: [-2.322, 0.255]MMRM
Comparison: Change from Baseline in WI-NRS at Week 2: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.96795% CI: [-1.921, 1.069]MMRM
Comparison: Change from Baseline in WI-NRS at Week 2: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.68495% CI: [-2.205, 0.762]MMRM
Comparison: Change from Baseline in WI-NRS at Week 4: Roflumilast Cream 0.05% vs. Vehicle Creamp-value: 0.85695% CI: [-2.221, 1.003]MMRM
Comparison: Change from Baseline in WI-NRS at Week 4: Roflumilast Cream 0.15% vs. Vehicle Creamp-value: 0.93295% CI: [-2.105, 1.089]MMRM