Atopic Dermatitis
Conditions
Keywords
Atopic dermatitis
Brief summary
The purpose of this study is to evaluate the effect of topical roflumilast on the reduction of atopic dermatitis lesions in adults with atopic dermatitis.
Interventions
DRUG0.5% Roflumilast Cream
Roflumilast 0.5% cream
DRUGVehicle Cream
Roflumilast formulation vehicle
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Is male or female between 18 to 65 years of age, inclusive, with atopic dermatitis (AD) meeting Hanifin and Rajka's criteria. 2. Has lesional skin areas of moderate severity characterized by modified local SCORing Atopic Dermatitis (SCORAD) of at least 4, with an erythema score ≥2, and confirmed by a qualified investigator. 3. Has an index/target lesion of moderate severity approximately 20 cm\^2, suitable for topical treatment. 4. Is willing to wash out from AD current active therapy prior to entry in the study. 5. Is willing and able to apply the study medication as directed, comply with study instructions and commit to all follow-up visits for the duration of the study. 6. If a male who is nonsterilized and sexually active with a female partner of childbearing potential, agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose. 7. If a female of childbearing potential who is sexually active with a nonsterilized male partner, agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose. 8. Is capable of understanding and complying with protocol requirements in the opinion of the investigator. 9. Signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.
Exclusion criteria
1. Has received any investigational compound within 30 days, or within 5 half-lives of the compound (whichever is longer) prior to the Screening visit. 2. Has a history of AD unresponsive or poorly responsive to topical treatments. 3. Has a history of hypersensitivity to phosphodiesterase (PDE)-4 inhibitors or to drugs of similar chemical classes or any inactive ingredients of the trial medication. 4. Has clinically significant abnormal hematological parameters of hemoglobin, hematocrit or erythrocytes at Screening, in the judgment of the investigator. 5. Has a history or current clinically relevant allergy or idiosyncrasy to drugs or food. 6. Had extensive exposure to ultraviolet (UV) light in the 4 weeks prior to first application of study medication, including tanning and sun beds or is intending to have such exposure during the study treatment that may interfere with the study assessments as judged by the investigator. 7. Has evidence of oozing of target lesion. 8. Has a current skin complication such as erythroderma or overt bacterial or viral infection for which treatment with anti-infectives are indicated. 9. Had systemic treatment with corticosteroids or retinoids for studied condition within 3 months prior to the first application of study medication. 10. Had topical or transdermal treatments, such as but not limited to retinoids, nicotine or hormone replacement therapies, on or near the intended site of application within 4 weeks prior to first application of study medication. 11. Had treatment with systemic/locally acting medications/procedures that might counter or influence the study aim within 4 weeks prior to first application of study medication and during the study (e.g., anti-histamines). 12. Has used emollients/moisturizers on areas to be treated within 24 hours prior to the first application of study medication. 13. Has used biologics at any time for treatment of AD. 14. Is currently enrolled in an investigational drug or device study. 15. Has any clinically significant illness that may influence the outcome of the trial from 4 weeks before Day 1 through trial completion. 16. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) values greater than 2.0 × upper limit of normal (ULN), or other clinically significant abnormal laboratory test that, in the opinion of the Investigator, would compromise the participant's ability to safely complete the trial. 17. Has a significant medical condition and/or conditions that, in the opinion of the Investigator, would interfere with the treatment, safety or compliance with the protocol. 18. Has a history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus. 19. Has a history of alcoholism or illicit drug abuse within 5 years prior to the Screening Visit or is currently consuming \>14 alcoholic drinks per week. 20. If female, is pregnant, nursing or planning a pregnancy during the study period. 21. Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study medication. This criterion does not apply to those participants with successfully resected basal cell or stage I squamous cell carcinoma of the skin. 22. Has a chronic or clinically relevant acute infection. 23. Has a history of depression associated with suicidal ideation and behavior. 24. Has hemodynamically significant cardiac arrhythmias or heart valve deformations. 25. Is an immediate family member, a study site employee, in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or at risk for consenting under duress. 26. Was institutionalized because of a legal or regulatory order.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 15 in Modified Local SCORing Atopic Dermatitis (SCORAD) | Baseline and Day 15 | Modified Local SCORAD is the sum of 5 individual indexes; erythema, edema/papulation, oozing/crusts, excoriations and lichenification scored on a 4 point scale, where 0=absent and 3=severe, with a total possible score of 15. Higher scores indicate greater severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 15 in Transepidermal Water Loss (TEWL) Values | Baseline and Day 15 | Diffusion of water through the skin is measured using a Tewameter. At each visit, 3 measurements are taken per treatment area (at 3 different areas of the target lesion). The TEWL value at each visit is the average of these measurements. |
| Change From Baseline to Day 15 in Participants' Assessment of Pruritus | Baseline and Day 15 | Severity of pruritus is assessed by the participants and recorded on a numeric scale ranging from 0 to 10, where 0 indicates the absence of the symptoms and 10 indicates the most severe symptoms. |
Countries
Germany
Participant flow
Recruitment details
Participants took part in the study at 3 centers in Germany from 10 June 2013 to 18 March 2014.
Pre-assignment details
Participants with a historical diagnosis of Atopic Dermatitis were enrolled in 1 of 2 twice daily (BID) treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| 0.5% Roflumilast Cream Roflumilast 0.5%, cream, topically, twice daily for up to 15 days. | 20 |
| Vehicle Cream Roflumilast formulation vehicle, cream, topically, twice daily for up to 15 days. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Total | Vehicle Cream | 0.5% Roflumilast Cream |
|---|---|---|---|
| Age, Continuous | 34.6 Years STANDARD_DEVIATION 10.66 | 36.5 Years STANDARD_DEVIATION 9.65 | 32.7 Years STANDARD_DEVIATION 11.5 |
| Baseline Modified Local SCORing Atopic Dermatitis (SCORAD) | 5.725 scores on a scale | 5.85 scores on a scale | 5.60 scores on a scale |
| Baseline Participant Assessment of Pruritis | 5.025 scores on a scale | 5.00 scores on a scale | 5.05 scores on a scale |
| Baseline Transepidermal Water Loss (TEWL) Mean | 41.52 g/m^2/hr | 41.57 g/m^2/hr | 41.47 g/m^2/hr |
| Body Mass Index (BMI) | 25.62 kg/m^2 STANDARD_DEVIATION 4.255 | 25.59 kg/m^2 STANDARD_DEVIATION 3.477 | 25.65 kg/m^2 STANDARD_DEVIATION 5.007 |
| Female Reproductive Status Female of childbearing potential | 20 participants | 11 participants | 9 participants |
| Female Reproductive Status N/A (male participant) | 20 participants | 9 participants | 11 participants |
| Female Reproductive Status Postmenopausal | 0 participants | 0 participants | 0 participants |
| Female Reproductive Status Surgically sterile | 0 participants | 0 participants | 0 participants |
| Gender Female | 20 Participants | 11 Participants | 9 Participants |
| Gender Male | 20 Participants | 9 Participants | 11 Participants |
| Height | 176.1 centimeters STANDARD_DEVIATION 9.66 | 174.9 centimeters STANDARD_DEVIATION 10.13 | 177.3 centimeters STANDARD_DEVIATION 9.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 20 Participants | 20 Participants |
| Region of Enrollment Germany | 40 Participants | 20 Participants | 20 Participants |
| Smoking Classificaiton Current smoker | 19 participants | 9 participants | 10 participants |
| Smoking Classificaiton Ex-Smoker | 8 participants | 3 participants | 5 participants |
| Smoking Classificaiton Never smoked | 13 participants | 8 participants | 5 participants |
| Weight | 80.02 kilograms STANDARD_DEVIATION 17.762 | 78.31 kilograms STANDARD_DEVIATION 12.965 | 81.72 kilograms STANDARD_DEVIATION 21.757 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 20 | 3 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Change From Baseline to Day 15 in Modified Local SCORing Atopic Dermatitis (SCORAD)
Modified Local SCORAD is the sum of 5 individual indexes; erythema, edema/papulation, oozing/crusts, excoriations and lichenification scored on a 4 point scale, where 0=absent and 3=severe, with a total possible score of 15. Higher scores indicate greater severity.
Time frame: Baseline and Day 15
Population: All randomized participants who received at least one application of any double-blind study medication with a score at Day 15. One subject in the 0.5% Roflumilast group was missing Day 15 data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.5% Roflumilast Cream | Change From Baseline to Day 15 in Modified Local SCORing Atopic Dermatitis (SCORAD) | -2.30 Scores on a scale | Standard Error 0.354 |
| Vehicle Cream | Change From Baseline to Day 15 in Modified Local SCORing Atopic Dermatitis (SCORAD) | -1.75 Scores on a scale | Standard Error 0.347 |
p-value: 0.27695% CI: [-1.5542, 0.4574]Mixed Models Analysis
Secondary
Change From Baseline to Day 15 in Participants' Assessment of Pruritus
Severity of pruritus is assessed by the participants and recorded on a numeric scale ranging from 0 to 10, where 0 indicates the absence of the symptoms and 10 indicates the most severe symptoms.
Time frame: Baseline and Day 15
Population: All randomized participants who received at least one application of any double-blind study medication with a score at Day 15. One subject in the 0.5% Roflumilast group was missing Day 15 data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.5% Roflumilast Cream | Change From Baseline to Day 15 in Participants' Assessment of Pruritus | -3.05 Scores on a scale | Standard Error 0.426 |
| Vehicle Cream | Change From Baseline to Day 15 in Participants' Assessment of Pruritus | -1.50 Scores on a scale | Standard Error 0.417 |
p-value: 0.01395% CI: [-2.7656, -0.3492]Mixed Models Analysis
Secondary
Change From Baseline to Day 15 in Transepidermal Water Loss (TEWL) Values
Diffusion of water through the skin is measured using a Tewameter. At each visit, 3 measurements are taken per treatment area (at 3 different areas of the target lesion). The TEWL value at each visit is the average of these measurements.
Time frame: Baseline and Day 15
Population: All randomized participants who received at least one application of any double-blind study medication with a score at Day 15. One subject in the 0.5% Roflumilast group was missing Day 15 data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.5% Roflumilast Cream | Change From Baseline to Day 15 in Transepidermal Water Loss (TEWL) Values | -18.60 g/m^2/hr | Standard Error 2.467 |
| Vehicle Cream | Change From Baseline to Day 15 in Transepidermal Water Loss (TEWL) Values | -12.69 g/m^2/hr | Standard Error 2.417 |
p-value: 0.09595% CI: [-12.9134, 1.0835]Mixed Models Analysis