Study Of Single And Ten Day Repeat Atopical Applications Of GW842470X Cream On The Skin Of Patients With Atopic Dermatitis

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00356642

Collaborator

(none)

Enrollment

Location

Arms

6.4

Actual Duration (Months)

7.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study of this study is to investigate the safety, tolerability and pharmacokinetics of GW842470X in patients with atopic dermatitis. GW842470X is an inhibitor of phosphodiesterase 4 (PDE4).

Condition or Disease	Intervention/Treatment	Phase
Dermatitis, Atopic	Drug: GW842470X Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Primary Purpose:

Treatment

Official Title:

A Randomised, Single-Blind, Dose-Rising Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Ten Day Repeat Topical Applications of GW842470X Cream on the Skin of Patients With Atopic Dermatitis

Actual Study Start Date :

Jun 10, 2005

Actual Primary Completion Date :

Dec 21, 2005

Actual Study Completion Date :

Dec 21, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single dose 1 cohort Subjects with body surface area (BSA) disease involvement between 10 and 15% will be included. Subjects will receive either 100 milligrams (mg) GW842470X or placebo in a ratio of 2:1.	Drug: GW842470X GW842470X will be available as a yellow smooth water-in-oil cream. Drug: Placebo GW842470X matching placebo will be available as a yellow smooth water-in-oil cream.
Experimental: Repeat dose 1 cohort Subjects with BSA disease involvement between 10 and 15% will be included. Subjects will receive either 100-150 mg GW842470X or placebo in a ratio of 3:1	Drug: GW842470X GW842470X will be available as a yellow smooth water-in-oil cream. Drug: Placebo GW842470X matching placebo will be available as a yellow smooth water-in-oil cream.
Experimental: Repeat dose 2 cohort Subjects with BSA disease involvement between 30 and 40% will be included. Subjects will receive either 300-400 mg GW842470X or placebo in a ratio of 3:1	Drug: GW842470X GW842470X will be available as a yellow smooth water-in-oil cream. Drug: Placebo GW842470X matching placebo will be available as a yellow smooth water-in-oil cream.
Experimental: Repeat dose 3 cohort Subjects with BSA disease involvement >=50% will be included. Subjects will receive either 500-1000 mg GW842470X or placebo in a ratio of 2:1	Drug: GW842470X GW842470X will be available as a yellow smooth water-in-oil cream. Drug: Placebo GW842470X matching placebo will be available as a yellow smooth water-in-oil cream.

Outcome Measures

Primary Outcome Measures

Number of subjects with abnormal physical examination findings [Up to Day 22]
Number of subjects with abnormal blood pressure [Up to Day 22]
Number of subjects with abnormal heart rate [Up to Day 22]
Number of subjects with abnormal 12-lead ECG assessment [Up to Day 22]
Number of subjects with abnormal findings on lead II cardiac monitoring [Up to Day 10]
Number of subjects with abnormal clinical laboratory tests [Up to Day 22]
AUC [Pre-dose, 1, 2, 4, 6, 8, 12 hours on Day 1, pre-dose on Days 3, 5, 7, 9 and pre-dose, 1, 2, 4, 6, 8, 12 , 24, 36 and 48 hours post-dose on Day 10]
Cmax [Pre-dose, 1, 2, 4, 6, 8, 12 hours on Day 1, pre-dose on Days 3, 5, 7, 9 and pre-dose, 1, 2, 4, 6, 8, 12 , 24, 36 and 48 hours post-dose on Day 10]

Secondary Outcome Measures

Time to max concentration and terminal half-life [Pre-dose, 1, 2, 4, 6, 8, 12 hours on Day 1, pre-dose on Days 3, 5, 7, 9 and pre-dose, 1, 2, 4, 6, 8, 12 , 24, 36 and 48 hours post-dose on Day 10]
SCORAD [Up to Day 10]
BSA determination [Up to Day 10]
clinical photography [Up to Day 10]
measurement of barrier function using trans-epidermal water loss (TEWL) [Up to Day 10]
skin biopsy (biomarkers CD4+, CD8+, eosinophils, total IgE) [Up to Day 10]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 67 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Atopic dermatitis patients (moderate to severe) who are otherwise healthy.
BMI range 18.5-29.9m2 at least 2 index lesions and BSA involvement >10%.
14 day washout of current therapy.

Exclusion criteria:

Patients who have had systemic treatment for atopic dermatitis or other topical or transdermal treatments (such as nicotine, hormone replacement therapies) within 14 days prior to first application of study medication and/or topical treatment with tar or any treatment with corticosteroids within 14 days prior to first application except 1% hydrocortisone.
Patients must not present with any systemic disorders or active skin disease other than atopic dermatitis.