A Study Assessing GW870086's Potential to Cause Skin Thinning

A Randomised, Double-blind (for GW870086), Placebo-controlled Study of Topical GW870086 Formulation to Explore the Potential for Skin Thinning in Healthy Adult Volunteers

This study is a randomised, double-blind, placebo-controlled study of topical GW870086 to explore the potential for skin thinning in healthy adult volunteers after 42±2 days of treatment. Twenty (20) healthy volunteers will be randomised to receive placebo and GW870086 2% cream, they will also receive either of the following treatments: GW870086 0.2% cream, or clobetasol propionate 0.05% cream.

Study Overview

• Status: Completed
• Conditions: Dermatitis, Atopic
• Intervention / Treatment: Drug: GW870086 0.2%; Drug: GW870086 2%; Drug: Placebo; Drug: Clobetasol Propionate

Detailed Description

This study is a randomised, double-blind, placebo-controlled study of topical GW870086 to explore the potential for skin thinning in healthy adult volunteers after 42±2 days of treatment. The primary objective of this study is to assess the thickness of the skin using ultrasound. The secondary objectives are to assess skin thinning using a visual scale for skin atrophy and telangiectasia, safety and tolerability of GW870086 and to assess the pharmacokinetics of GW870086 administered as a cream for 42±2 days.

Twenty (20) healthy volunteers will be randomised to receive placebo and GW870086 2% cream. They will also receive either of the following treatments: GW870086 0.2% cream, or clobetasol propionate 0.05% cream. Subjects will apply all 3 treatments once daily during the 42±2 day treatment period. However subjects who are randomised to receive the unblinded clobetasol propionate will only apply this once daily for a maximum of 21±2 days but will continue to dose with the other 2 treatments. If significant evidence of skin thinning is observed in any of the treatment arms (25% reduction in skin thickness measured using ultrasound) then application of this treatment will be discontinued. Three areas of approximately 5 x 5 cm on the arm will be identified and each treatment will be applied to the same area throughout the 42±2 day treatment period.

• Study Type: Interventional
• Enrollment (Actual): 20
• 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 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• AST (Aspartate aminotransferase), ALT (Alanine aminotransferase), alkaline phosphatase and bilirubin ≤ 1.5xULN (Upper limit of normal)(isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Healthy as determined by an experienced physician.
• Male or female between 18 and 55 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).
• Capable of giving written informed consent.
• Single QTc, QTcB < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

• Any sign of weak or fragile skin, striae, or similar, in the areas which will be evaluated.
• Tattoos or body art on the upper arms.
• Foreseeable intensive UV exposure during the study (solar or artificial). Subjects must not be exposed to direct sunlight or skin tanning devices (e.g. sunbed) for the duration of the study.
• A positive pre-study test for Hepatitis B or Hepatitis C antibody within 3 months of screening.
• 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 (Human Immunodeficiency Virus) 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.
• History of sensitivity to any of the study medications or components thereof.
• 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.
• Subjects who are kept due to regulatory or juridical order in an institution.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GW870086 0.2% & GW870086 2%; GW870086 0.2%, 2% & placebo each applied to an identified area for 42 days.	Drug: GW870086 0.2%; White to slightly coloured opaque cream; Drug: GW870086 2%; White to slightly coloured opaque cream; Drug: Placebo; White to slightly coloured opaque cream
Experimental: GW870086 2% & Clobetasol Propionate; GW870086 2% & placebo applied to an identified area for 42 days, while Clobetasol Propionate is applied to an area for 21 days	Drug: GW870086 2%; White to slightly coloured opaque cream; Drug: Placebo; White to slightly coloured opaque cream; Drug: Clobetasol Propionate; White cream

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in skin thickness using ultrasound between GW870086 (0.2% and 2%) versus placebo	Days; 1, 14, 21, 28, 42, 43

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical evaluation of treated skin areas using assessment of clinical signs and symptoms according to the visual scores of skin atrophy and telangiectasia	Days; 7, 14, 21, 28, 35, 42, 43
The assessment of safety parameters; adverse events, clinical laboratory tests, ECG, and vital signs	6 weeks
Plasma concentrations of GW870086	Days 14 & 42
Cmax of GW870086	Days 14 & 42
Tmax of GW870086	Days 14 & 42
AUC of GW870086	Days 14 & 42

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2011
• Primary Completion (Actual): July 7, 2011
• Study Completion (Actual): July 7, 2011

Study Registration Dates

• First Submitted: June 16, 2011
• First Submitted That Met QC Criteria: June 23, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Dermatitis, Atopic; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Clobetasol
• Other Study ID Numbers: 113435

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 113435
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 113435
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 113435
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 113435
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 113435
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 113435
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 113435
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register