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A Study Assessing GW870086's Potential to Cause Skin Thinning

Phase 1
Completed
Conditions
Dermatitis, Atopic
Interventions
Drug: GW870086 0.2%
Drug: GW870086 2%
Drug: Placebo
Registration Number
NCT01381445
Lead Sponsor
GlaxoSmithKline
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
GW870086 0.2% &amp; GW870086 2%GW870086 0.2%GW870086 0.2%, 2% \&amp; placebo each applied to an identified area for 42 days.
GW870086 0.2% &amp; GW870086 2%PlaceboGW870086 0.2%, 2% \&amp; placebo each applied to an identified area for 42 days.
GW870086 0.2% &amp; GW870086 2%GW870086 2%GW870086 0.2%, 2% \&amp; placebo each applied to an identified area for 42 days.
GW870086 2% &amp; Clobetasol PropionateGW870086 2%GW870086 2% \&amp; placebo applied to an identified area for 42 days, while Clobetasol Propionate is applied to an area for 21 days
GW870086 2% &amp; Clobetasol PropionateClobetasol PropionateGW870086 2% \&amp; placebo applied to an identified area for 42 days, while Clobetasol Propionate is applied to an area for 21 days
GW870086 2% &amp; Clobetasol PropionatePlaceboGW870086 2% \&amp; placebo applied to an identified area for 42 days, while Clobetasol Propionate is applied to an area for 21 days
Primary Outcome Measures
NameTimeMethod
Change from baseline in skin thickness using ultrasound between GW870086 (0.2% and 2%) versus placeboDays; 1, 14, 21, 28, 42, 43
Secondary Outcome Measures
NameTimeMethod
Clinical evaluation of treated skin areas using assessment of clinical signs and symptoms according to the visual scores of skin atrophy and telangiectasiaDays; 7, 14, 21, 28, 35, 42, 43
The assessment of safety parameters; adverse events, clinical laboratory tests, ECG, and vital signs6 weeks
Cmax of GW870086Days 14 & 42
Tmax of GW870086Days 14 & 42
Plasma concentrations of GW870086Days 14 &amp; 42
AUC of GW870086Days 14 & 42

Trial Locations

Locations (1)

GSK Investigational Site

🇩🇪

Berlin, Germany

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