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

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

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).

Study Overview

• Status: Completed
• Conditions: Dermatitis, Atopic
• Intervention / Treatment: Drug: GW842470X; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 67 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Ishikawa N, Hattori N, Kohno N, Kobayashi A, Hayamizu T, Johnson M. Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls. Int J Chron Obstruct Pulmon Dis. 2015 Jan 23;10:185-92. doi: 10.2147/COPD.S74557. eCollection 2015.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2005
• Primary Completion (Actual): December 21, 2005
• Study Completion (Actual): December 21, 2005

Study Registration Dates

• First Submitted: July 25, 2006
• First Submitted That Met QC Criteria: July 25, 2006
• First Posted (Estimate): July 26, 2006

Study Record Updates

• Last Update Posted (Actual): September 29, 2017
• Last Update Submitted That Met QC Criteria: September 27, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: tolerability; safety; PK; Atopic Dermatitis; PD; GW842470X
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: TPD102031