Topical Roflumilast in Adults With Atopic Dermatitis

A Phase 2a, 15-Day, Randomized, Parallel Group, Double-Blind, Multi-Centre, Vehicle Controlled Trial to Assess the Efficacy and Local Safety of a Cream Containing 0.5% Roflumilast - a Phosphodiesterase Type 4 Inhibitor (PDE4i) Dermal Formulation - on Atopic Dermatitis Patients With Skin Lesions of Moderate Severity

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.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: 0.5% Roflumilast Cream; Drug: Vehicle Cream

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
  • Gera, Germany
  • Hamburg, Germany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.5% Roflumilast Cream; Roflumilast 0.5%, cream, topically, twice daily for up to 15 days.	Drug: 0.5% Roflumilast Cream; Roflumilast 0.5% cream
Placebo Comparator: Vehicle Cream; Roflumilast formulation vehicle, cream, topically, twice daily for up to 15 days.	Drug: Vehicle Cream; Roflumilast formulation vehicle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Day 15
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.	Baseline and Day 15

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: May 14, 2013
• First Submitted That Met QC Criteria: May 14, 2013
• First Posted (Estimate): May 17, 2013

Study Record Updates

• Last Update Posted (Estimate): February 1, 2017
• Last Update Submitted That Met QC Criteria: December 2, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Atopic dermatitis
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: ROF-DERM_203; 2012-003000-12 (EudraCT Number); U1111-1133-6455 (Registry Identifier: UTN (WHO))