Back to resultsCombination Therapy for Atopic Dermatitis
Primary Purpose
Atopic Dermatitis
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Combination of pimecrolimus and fluticasone
pimecrolimus
Sponsored by
About this trial
This is an interventional treatment trial for Atopic Dermatitis focused on measuring THerapy for acute moderate to severe flares
Eligibility Criteria
Inclusion Criteria: Age 2 to 65 years Clinical diagnosis of (Atopic Dermatitis) AD according to the American Academy of Dermatology (AAD) Consensus Conference (2001) At least two lesions of AD on symmetrical part of the body (same location for each side of the body), of severe intensity (m-EASI is at least 7 on each site, with erythema of at least 3 (severe) and papulation/infiltration of at least 3 (severe)) and similar severity (m-EASI does not differ from more than 2 points on both sides) Signed written informed consent Willingness and ability to comply with the study requirements Female is able to enter and participate in this study if she is of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or Childbearing potential, has a negative pregnancy test (urine) at the screen visit and agrees to an adequate method of birth control throughout the study (which may, at the investigator's discretion, include abstinence) Exclusion Criteria: History of immune deficiencies or history of malignant disease Patients with moderate to severe lichenification at the target areas (i.e. score 2 or 3) Active cutaneous bacterial, viral or fungal infections in target areas History of other skin disorders, including Netherton syndrome, that could interfere with the evaluations Use of any topical treatment known or suspected to have an effect on atopic dermatitis within one week prior to the screen visit (except for calcineurin inhibitors, for which the washout is 2 weeks) Use of any systemic treatment (including phototherapy) known or suspected to have an effect on AD within four weeks prior to the screen visit [(patients on a stable and low dose of inhaled steroids, on a stable dose of anti histamines, on stable dose of leukotriene antagonists, or receiving occasional short-acting b2-agonists for the treatment of asthma and topical corticosteroids (nasal spray) for the treatment of allergic rhinitis may participate). High-dose inhaled corticosteroids (> 440 mcg of fluticasone a day) and anti-IgE products are not permitted]. Known sensitivity to pimecrolimus or vehicle (placebo) or fluticasone propionate cream or any of their ingredients Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study Use of any other investigational agent in the last 30 days
Sites / Locations
- National Jewish Research Medical Center
- Northwestern University School of Medicine
- University of Texas at Houston Medical School
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
placebo
pimecrolimus cream
Arm Description
Placebo cream
Outcomes
Primary Outcome Measures
Change From Baseline in the m-EASI (Eczema Area Severity Index) Score.
Eczema Area severity index (EASI) is a composition of scores based on area of eczema involved, (0 = mild to 3 = severe) for four separate Atopic Dermatitis (AD) symptoms: erythema,infiltration ⁄population, excoriation and ichenification.
Total score 0-12
Secondary Outcome Measures
The Time to Clearance of the Disease
The time to clearance of eczema measured in days
The Time to the First Day When m-EASI is Scored by the Investigator as 2 or Less
Time to partial clearance of the localized eczema lesion assessed by the investigator is measured in days
The Percentage of Target Areas Reaching a l-IGA (Localized Investigator Global Assessment (l-IGA) or 0 or 1)
The Investigator Global Assessment (IGA) and l-IGA were graded on a scale of 0-4 (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe). The percentage of eczema lesions from the total population that reach almost clear
The Percentage of Target Areas Improved (i.e., Decrease in Localized Investigator Global Assessmet (l-IGA) Score From Baseline)
The percentage of eczema areas that show improvement in l-IGA score.
The l-IGA were graded on a scale of 0-4 (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease).
The Percentage of Target Areas Reaching a m-EASI (Modifed-Eczema Area Severity Index) Score of 2 or Less
The EASI is a measure of Atopic Dermatitis (AD) severity. A m-EASI score (0-12) was also calculated as the sum of severity (0 = mild to 3 = severe) for four separate AD symptoms: erythema, infiltration ⁄population, excoriation and lichenification.
The percentage of participants whose eczema reaches almost clear
Change From Baseline in Patients' Self Assessment of Disease Severity (PSA) of Target Areas
The patient or caregiver assessment of eczema severity (PSA) was recorded daily in a diary using a 0-4 scale similar to that of the IGA.(0 = clear,
1 = almost clear, 2 = mild disease, 3 = moderate disease,4 = severe disease).
Difference in value of PSA from baseline to end of study
Full Information
NCT ID
NCT00119158
First Posted
July 5, 2005
Last Updated
July 23, 2010
Sponsor
Children's Hospital of Philadelphia
Collaborators
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00119158
Brief Title
Combination Therapy for Atopic Dermatitis
Official Title
An Exploratory Double-blind, Randomized, Vehicle-controlled, Paired Study to Evaluate the Efficacy and Safety of Concomitant Use of Elidel Cream 1% and Cutivate Cream 0.05% in Patients With Severe Lesions of Atopic Dermatitis (AD)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2010
Overall Recruitment Status
Completed
Study Start Date
October 2004 (undefined)
Primary Completion Date
June 2005 (Actual)
Study Completion Date
June 2005 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Children's Hospital of Philadelphia
Collaborators
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Atopic dermatitis is a chronic relapsing disease with acute flares. The standard therapy is to treat acute flares using topical medications. The two most common classes of topical medications for atopic dermatitis (AD) are topical corticosteroids and topical calcineurin inhibitors.
Pimecrolimus and topical corticosteroids exert their activity by different mechanisms, there may be a synergistic effect of the combination therapy. Therefore, a combination therapy may provide a faster resolution of severe skin lesions and consequently reduce the duration of the topical corticosteroid treatment. Another benefit of the combination therapy maybe the use of a lower potency corticosteroid to achieve the same degree of clearance.
The hypothesis of this trial is that the combination of the two agents will lead to faster clearance than the single agent of topical corticosteroids.
Detailed Description
This trial is a double-blind controlled trial of fluticasone cream daily and pimecrolimus cream BID versus fluticasone cream daily and placebo cream BID for the treatment of acute flares of atopic dermatitis.
While pimecrolimus cream 1% has been proven to be effective in mild and moderate Atopic dermatitis (AD), there is a need for a fast control of severe skin lesions. On the other hand, reducing the duration of the topical corticosteroid treatment is a reasonable approach to minimize the occurrence of adverse effects.
Because pimecrolimus and topical corticosteroids exert their activity by different mechanisms, there may be a synergistic effect of the combination therapy. Therefore, a combination therapy may provide a faster resolution of severe skin lesions and consequently reduce the duration of the topical corticosteroid treatment. Another benefit of the combination therapy maybe the use of a lower potency corticosteroid to achieve the same degree of clearance.
In vitro data have demonstrated that a combination of steroids and tacrolimus has synergistic effects on in vitro human lymphocyte proliferation. In addition, it has previously been reported, in a pilot investigation in two subjects, that a combination regimen of pimecrolimus 1% twice a day and fluticasone propionate cream 0.05% once daily was superior to fluticasone propionate cream 0.05% once daily in the acute treatment of atopic dermatitis (AD).
This study is conducted to validate these findings in a larger number of patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis
Keywords
THerapy for acute moderate to severe flares
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Placebo cream
Arm Title
pimecrolimus cream
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Combination of pimecrolimus and fluticasone
Other Intervention Name(s)
Pimecrolimus cream, fluticasone
Intervention Description
Pimecrolimus cream twice a day and fluticasone cream once a day
Intervention Type
Drug
Intervention Name(s)
pimecrolimus
Intervention Description
apply daily with fluticasone cream for flares
Primary Outcome Measure Information:
Title
Change From Baseline in the m-EASI (Eczema Area Severity Index) Score.
Description
Eczema Area severity index (EASI) is a composition of scores based on area of eczema involved, (0 = mild to 3 = severe) for four separate Atopic Dermatitis (AD) symptoms: erythema,infiltration ⁄population, excoriation and ichenification.
Total score 0-12
Time Frame
up to 15 days
Secondary Outcome Measure Information:
Title
The Time to Clearance of the Disease
Description
The time to clearance of eczema measured in days
Time Frame
assessed up to 30 days following drug application
Title
The Time to the First Day When m-EASI is Scored by the Investigator as 2 or Less
Description
Time to partial clearance of the localized eczema lesion assessed by the investigator is measured in days
Time Frame
up to one week
Title
The Percentage of Target Areas Reaching a l-IGA (Localized Investigator Global Assessment (l-IGA) or 0 or 1)
Description
The Investigator Global Assessment (IGA) and l-IGA were graded on a scale of 0-4 (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe). The percentage of eczema lesions from the total population that reach almost clear
Time Frame
up to 15 days
Title
The Percentage of Target Areas Improved (i.e., Decrease in Localized Investigator Global Assessmet (l-IGA) Score From Baseline)
Description
The percentage of eczema areas that show improvement in l-IGA score.
The l-IGA were graded on a scale of 0-4 (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease).
Time Frame
up to 15 days
Title
The Percentage of Target Areas Reaching a m-EASI (Modifed-Eczema Area Severity Index) Score of 2 or Less
Description
The EASI is a measure of Atopic Dermatitis (AD) severity. A m-EASI score (0-12) was also calculated as the sum of severity (0 = mild to 3 = severe) for four separate AD symptoms: erythema, infiltration ⁄population, excoriation and lichenification.
The percentage of participants whose eczema reaches almost clear
Time Frame
up to one week
Title
Change From Baseline in Patients' Self Assessment of Disease Severity (PSA) of Target Areas
Description
The patient or caregiver assessment of eczema severity (PSA) was recorded daily in a diary using a 0-4 scale similar to that of the IGA.(0 = clear,
1 = almost clear, 2 = mild disease, 3 = moderate disease,4 = severe disease).
Difference in value of PSA from baseline to end of study
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 2 to 65 years
Clinical diagnosis of (Atopic Dermatitis) AD according to the American Academy of Dermatology (AAD) Consensus Conference (2001)
At least two lesions of AD on symmetrical part of the body (same location for each side of the body), of severe intensity (m-EASI is at least 7 on each site, with erythema of at least 3 (severe) and papulation/infiltration of at least 3 (severe)) and similar severity (m-EASI does not differ from more than 2 points on both sides)
Signed written informed consent
Willingness and ability to comply with the study requirements
Female is able to enter and participate in this study if she is of:
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or
Childbearing potential, has a negative pregnancy test (urine) at the screen visit and agrees to an adequate method of birth control throughout the study (which may, at the investigator's discretion, include abstinence)
Exclusion Criteria:
History of immune deficiencies or history of malignant disease
Patients with moderate to severe lichenification at the target areas (i.e. score 2 or 3)
Active cutaneous bacterial, viral or fungal infections in target areas
History of other skin disorders, including Netherton syndrome, that could interfere with the evaluations
Use of any topical treatment known or suspected to have an effect on atopic dermatitis within one week prior to the screen visit (except for calcineurin inhibitors, for which the washout is 2 weeks)
Use of any systemic treatment (including phototherapy) known or suspected to have an effect on AD within four weeks prior to the screen visit [(patients on a stable and low dose of inhaled steroids, on a stable dose of anti histamines, on stable dose of leukotriene antagonists, or receiving occasional short-acting b2-agonists for the treatment of asthma and topical corticosteroids (nasal spray) for the treatment of allergic rhinitis may participate). High-dose inhaled corticosteroids (> 440 mcg of fluticasone a day) and anti-IgE products are not permitted].
Known sensitivity to pimecrolimus or vehicle (placebo) or fluticasone propionate cream or any of their ingredients
Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study
Use of any other investigational agent in the last 30 days
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan M Spergel, MD, PhD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Jewish Research Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Northwestern University School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Texas at Houston Medical School
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
Citation
Spergel J, Hultsch T. Pimecrolimus cream 1% and fluticasone propionate cream 0.05% versus fluticasone propionate cream 0.05% for the treatment of flares of atopic dermatitis. 28th Annual Hawaii Dermatology Seminar, 2004
Results Reference
background
PubMed Identifier
14991059
Citation
Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004 Mar;113(5):651-7. doi: 10.1172/JCI21060.
Results Reference
background
PubMed Identifier
10468798
Citation
Grassberger M, Baumruker T, Enz A, Hiestand P, Hultsch T, Kalthoff F, Schuler W, Schulz M, Werner FJ, Winiski A, Wolff B, Zenke G. A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol. 1999 Aug;141(2):264-73. doi: 10.1046/j.1365-2133.1999.02974.x.
Results Reference
background
PubMed Identifier
14568846
Citation
Eichenfield LF, Lucky AW, Boguniewicz M, Langley RG, Cherill R, Marshall K. 1% pimecrolimus cream for atopic dermatitis. Arch Dermatol. 2003 Oct;139(10):1369-70; author reply 1370-1. doi: 10.1001/archderm.139.10.1369. No abstract available.
Results Reference
background
PubMed Identifier
12093983
Citation
Wahn U, Bos JD, Goodfield M, Caputo R, Papp K, Manjra A, Dobozy A, Paul C, Molloy S, Hultsch T, Graeber M, Cherill R, de Prost Y; Flare Reduction in Eczema with Elidel (Children) Multicenter Investigator Study Group. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Pediatrics. 2002 Jul;110(1 Pt 1):e2. doi: 10.1542/peds.110.1.e2.
Results Reference
background
PubMed Identifier
7544367
Citation
Lee MJ, Pyszczynski N, Jusko WJ. Combined inhibition effects of tacrolimus and methylprednisolone on in vitro human lymphocyte proliferation. Immunopharmacol Immunotoxicol. 1995 May;17(2):335-45. doi: 10.3109/08923979509019755.
Results Reference
background
PubMed Identifier
11168575
Citation
Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 2001 Feb;10(1):11-8. doi: 10.1034/j.1600-0625.2001.100102.x.
Results Reference
background
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Combination Therapy for Atopic Dermatitis
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