Combination Therapy for Atopic Dermatitis

This study has been completed.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by:
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT00119158
First received: July 5, 2005
Last updated: July 23, 2010
Last verified: July 2010
  Purpose

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.


Condition Intervention Phase
Atopic Dermatitis
Drug: Combination of pimecrolimus and fluticasone
Drug: pimecrolimus
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Change From Baseline in the m-EASI (Eczema Area Severity Index) Score. [ Time Frame: up to 15 days ] [ Designated as safety issue: No ]

    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 [ Time Frame: assessed up to 30 days following drug application ] [ Designated as safety issue: No ]
    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 Frame: up to one week ] [ Designated as safety issue: No ]
    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) [ Time Frame: up to 15 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: up to 15 days ] [ Designated as safety issue: No ]

    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 [ Time Frame: up to one week ] [ Designated as safety issue: No ]

    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 [ Time Frame: 30 days ] [ Designated as safety issue: No ]

    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



Enrollment: 90
Study Start Date: October 2004
Study Completion Date: June 2005
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
Placebo cream
Drug: pimecrolimus
apply daily with fluticasone cream for flares
Other Name: Pimecrolimus
Active Comparator: pimecrolimus cream Drug: Combination of pimecrolimus and fluticasone
Pimecrolimus cream twice a day and fluticasone cream once a day
Other Names:
  • Pimecrolimus cream
  • fluticasone
Drug: pimecrolimus
apply daily with fluticasone cream for flares
Other Name: Pimecrolimus

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.

  Eligibility

Ages Eligible for Study:   2 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00119158

Locations
United States, Colorado
National Jewish Research Medical Center
Denver, Colorado, United States, 80206
United States, Illinois
Northwestern University School of Medicine
Chicago, Illinois, United States, 60611
United States, Texas
University of Texas at Houston Medical School
Houston, Texas, United States, 77030
Sponsors and Collaborators
Children's Hospital of Philadelphia
Novartis Pharmaceuticals
Investigators
Principal Investigator: Jonathan M Spergel, MD, PhD Children's Hospital of Philadelphia
  More Information

Publications:
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

Responsible Party: Jonathan Spergel, The Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00119158     History of Changes
Other Study ID Numbers: 2004-10-3975
Study First Received: July 5, 2005
Results First Received: February 19, 2010
Last Updated: July 23, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
THerapy for acute moderate to severe flares

Additional relevant MeSH terms:
Dermatitis
Dermatitis, Atopic
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Pimecrolimus
Tacrolimus
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 18, 2014