A Study to Test the Effect of 2 Different Doses of Topical GW870086X on Atopic Dermatitis Also Including a Postive Control and a Placebo
Condition: Dermatitis, Atopic
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Intervention: GW870086 2.0%; GW870086 0.2%; FP 0.05%; Placebo
Intervention description: White to slightly colored opaque cream; White to slightly colored opaque cream; White cream; White to slightly colored opaque cream
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Atopic Dermatitis; GW870086X; TIS; IGA

Summary:

      This study is a randomised, double-blind, placebo-controlled study to assess the efficacy of
      GW870086X cream formulation in subjects with moderate to severe atopic dermatitis. Subjects
      will be assigned to take 3 out of the 4 possible treatments for 21 ±2 days: GW870086X 0.2%
      cream, GW870086X 2% cream, FP 0.05% cream (as a positive control) and placebo cream. All
      subjects will be randomised to receive placebo cream. Three index lesions located on the arms
      and/or legs (one on each) will be identified per subject and each treatment will be applied
      to the same lesion.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with a diagnosis of atopic dermatitis who are otherwise healthy.

          -  Male or female between 18 and 65 years of age inclusive.

          -  A female subject is eligible to participate if she is of:

             • Non-childbearing potential defined as pre-menopausal females with a documented tubal
             ligation or hysterectomy; or postmenopausal. Females on hormone replacement therapy
             (HRT) and whose menopausal status is in doubt will be required to use one of the
             protocol contraception methods if they wish to continue their HRT during the study.

          -  Male subjects with female partners of child-bearing potential must agree to use one of
             the protocol contraception methods.

          -  BMI within the range 19.0 - 29.0 kg/m2 (inclusive).

          -  Subjects must have body surface area (BSA) disease involvement of >5% as assessed by
             the rule of nines method.

          -  Patients must be willing to refrain from current active therapy for at least 10 days
             prior to dosing,

          -  Capable of giving written informed consent.

          -  Single QTc, QTcB < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

          -  AST and ALT < 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin
             >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

        Exclusion Criteria:

          -  The subject presents with any systemic disorder, active skin disease or subjects who
             present with scars, moles, tattoos, body piercings, sunburn in the test area which
             could interfere with the assessment of lesions at screening.

          -  The subject has atopic dermatitis restricted to the face, the feet or the hands only.

          -  The subject has a current complication of atopic dermatitis for which treatment with
             anti-infectives are indicated.

          -  History of recent (< 6 months) active or presence of current superficial skin
             infections of viral aetiology

          -  The subject has been diagnosed as having contact dermatitis in area of target lesions,
             seborrheic dermatitis and/or occupational eczema at predilection sites of atopic
             dermatitis.

          -  The subject has had topical or transdermal treatments on or near the intended site of
             application within 14 days prior to first application of study medication.

          -  The subject has had systemic treatment for atopic dermatitis within 28 days of the
             first dose of study medication.

          -  Foreseeable intensive UV exposure during the study. Subjects must not be exposed to
             direct sunlight or skin tanning devices for the duration of the study.

          -  The subject has used topical treatment with tar or any corticosteroid within 14 days
             of the first dose of study medication except topical 1% hydrocortisone which may be
             used twice daily in patients with severe disease who require step-down therapy during
             the wash-out period until 3 days prior to study start, after which the hydrocortisone
             must be discontinued.

          -  The subject has used topical treatment with buproprion within 14 days of the first
             dose of study medication.

          -  History of cutaneous photodisorder.

          -  History of allergy to steroids or components of test medications.

          -  History or presence of skin (other than atopic dermatitis), hepatic or renal disease
             or any other condition known to interfere with absorption, distribution, metabolism or
             excretion of drugs.

          -  Subjects with a history of diaphoresis/excessive sweating not restricted to palms or
             face.

          -  A positive test for Hepatitis B or Hepatitis C antibody.

          -  Current or chronic history of liver disease, or known hepatic or biliary
             abnormalities.

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for HIV antibody.

          -  History of regular alcohol consumption within 6 months of the study.

          -  The subject has participated in a clinical trial and has received an investigational
             product within the following time period prior to the first dosing day in the current
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer).

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.

          -  Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
             supplements within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5
             half-lives (whichever is longer) prior to the first dose of study medication, unless
             in the opinion of the Investigator and GSK Medical Monitor the medication will not
             interfere with the study procedures or compromise subject safety.

          -  Where participation in the study would result in donation of blood or blood products
             in excess of 500 mL within a 56 day period.

          -  Unwillingness or inability to follow the procedures outlined in the protocol.

          -  Subject is mentally or legally incapacitated.

          -  History of sensitivity to heparin or heparin-induced thrombocytopenia.

          -  Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or
             pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior
             to the first dose of study medication.