Combination Therapy for Atopic Dermatitis

• ClinicalTrials.gov Identifier: NCT00119158
• Recruitment Status: Completed
• First Posted: July 13, 2005
• Results First Posted: July 22, 2010
• Last Update Posted: July 27, 2010
• Sponsor: Children's Hospital of Philadelphia
• Collaborator: Novartis Pharmaceuticals
• Information provided by: Children's Hospital of Philadelphia

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.

Condition or disease	Intervention/treatment	Phase
Atopic Dermatitis	Drug: Combination of pimecrolimus and fluticasone; Drug: pimecrolimus	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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)
• Study Start Date: October 2004
• Actual Primary Completion Date: June 2005
• Actual Study Completion Date: June 2005

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: placebo; Placebo cream	Drug: pimecrolimus; apply daily with fluticasone cream for flares
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

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in the m-EASI (Eczema Area Severity Index) Score. [ Time Frame: up to 15 days ]

   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 :

1. The Time to Clearance of the Disease [ Time Frame: assessed up to 30 days following drug application ]
   The time to clearance of eczema measured in days
2. The Time to the First Day When m-EASI is Scored by the Investigator as 2 or Less [ Time Frame: up to one week ]
   Time to partial clearance of the localized eczema lesion assessed by the investigator is measured in days
3. 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 ]
   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
4. 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 ]

   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).

5. 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 ]

   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

6. Change From Baseline in Patients' Self Assessment of Disease Severity (PSA) of Target Areas [ Time Frame: 30 days ]

   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

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004 Mar;113(5):651-7. Review.

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.

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.

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.

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.

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.

• Responsible Party: Jonathan Spergel, The Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT00119158
• Other Study ID Numbers: 2004-10-3975
• First Posted: July 13, 2005
• Results First Posted: July 22, 2010
• Last Update Posted: July 27, 2010
• Last Verified: July 2010

Keywords provided by Children's Hospital of Philadelphia:

THerapy for acute moderate to severe flares

Additional relevant MeSH terms:

Dermatitis, Atopic; Dermatitis; Eczema; Skin Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Fluticasone; Xhance; Pimecrolimus; Tacrolimus; Anti-Inflammatory Agents; 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