We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Test the Effect of 2 Different Doses of Topical GW870086X on Atopic Dermatitis Also Including a Postive Control and a Placebo

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01299610
First Posted: February 18, 2011
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
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.

Condition Intervention Phase
Dermatitis, Atopic Drug: GW870086 2.0% Drug: GW870086 0.2% Drug: FP 0.05% Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled Study of Topical GW870086X Formulation in Subjects With Moderate or Severe Atopic Dermatitis

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline Three Item Severity (TIS) Scores Between GW870086 (0.2% and 2%) Versus Placebo at Day 22 [ Time Frame: Baseline (Day 1) and Day 22 ]
    Three target lesions were selected and each of the 3 target lesions were assessed separately using the TIS for erythema, oedema/papulation, and excoriation using a score of 0 - 3 as 0 = absent, 1 = mild, 2 = moderate, 3 = severe. Each participant had at least 3 index lesions (=> 1square centimeter in size) with a sum score of =>4 and =< 6 for erythema, oedema/populations and excoriations using the TIS rating scale at screening. The index lesions represented common lesions i.e. not the most or least severe lesions. The total TIS score for a lesion was calculated as the sum of each of the component scores i.e. ranging from 0 (no symptoms) to 9 (severe symptoms). The values of Day 1 assessments were considered as Baseline values. The change from Baseline was calculated by subtracting the Baseline TIS score from Day 22 TIS score.


Secondary Outcome Measures:
  • Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 [ Time Frame: Days 2, 3, 7, and 14 ]
    Three target lesions were selected and each of the 3 target lesions were assessed separately using the TIS for erythema, oedema/papulation, and excoriation using a score of 0 - 3 as 0 = absent, 1 = mild, 2 = moderate, 3 = severe. Each participant had at least 3 index lesions (=> 1square centimeter in size) with a sum score of =>4 and =< 6 for erythema, oedema/populations and excoriations using the TIS rating scale at screening. The index lesions represented common lesions i.e. not the most or least severe lesions. The total TIS score for a lesion was calculated as the sum of each of the component scores i.e. may range from 0 (no symptoms) to 9 (severe symptoms). The values of Day 1 assessments were considered as Baseline values. The change from Baseline was calculated by subtracting the Baseline TIS score from Day 22 values TIS score.

  • Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 [ Time Frame: Days 2, 3, 7, 14 and 22 ]
    Three target lesions were selected and each of the 3 target lesions were assessed separately using the IGA. The IGA was carried out by a trained dermatologist and score ranged from 0 to 5. The detailed IGA scale is as: 0-Clear: No inflammatory signs of atopic dermatitis, 1- Almost clear: Just perceptible erythema and just perceptible apulation/infiltration, 2-Mild: Mild erythema and mild papulation/infiltration, 3-Moderate: Moderate erythema, and moderate papulation/infiltration, 4-Severe: Severe erythema and severe papulation/infiltration, 5-Very Severe: Very severe erythema, and very severe papulation/infiltration with oozing/crusting. The participant was considered as responder if each lesion at timepoint, IGA score reduced by 1 grade and improved from Baseline by 2 grades.

  • Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Upto Day 21 ]
    AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Number of participants with AEs and SAEs were reported.

  • Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) [ Time Frame: Up to Day 21 ]
    Laboratory ranges of PCI represented as multiplier of lower limit of normal [LLN]; Multipliers of upper limit of normal (ULN). Laboratory ranges of PCI for white blood cell count (0.67×LLN; 1.82×ULN), neutrophil count (0.83×ULN), hemoglobin for male (1.03×ULN) and for female (1.13×ULN), hematocrit for male (1.02×ULN) for female (1.17×ULN), platelet count (0.67×LLN; 1.57), lymphocytes (0.81×LLN), albumin (0.86 ×LLN), calcium (0.91×LLN; 1.06×ULN), glucose (0.71×LLN; 1.41×ULN), potassium (0.86×LLN; 1.10×ULN), sodium (0.96×LLN; 1.03×ULN), aspartate amino transferase (>= 2x ULN), alanine transaminase (>=2x ULN), alkaline Phosphatase (>=2x ULN), total bilirubin (>=1.5x ULN). Only those parameters for which at least one value of PCI was reported are summarized. The number of participants with PCI hematology and clinical chemistry findings at any visit during the treatment and follow-up were reported.

  • Number of Participants With Abnormal Electrocardiogram (ECG) of PCI [ Time Frame: Up to Day 21 ]
    12-lead ECG was obtained. The standard ECG criteria of PCI were 1) absolute QTc Interval, > 450 milliseconds (msec), 2) increase from Baseline in QTc > 60 msec 3) absolute PR Interval, <110 and >220 msec, 4) absolute QRS Interval, < 75 and >110 msec. The number of participants with PCI ECG findings at any visit during the treatment and follow-up were reported.

  • Number of Participants With Abnormal Vital Signs (Systolic and Diastolic Blood Pressure and Pulse Rate) of PCI [ Time Frame: Up to Day 21 ]
    The PCI ranges (low and high) of the vital sign parameters were for systolic blood pressure (<85 and >160 millimeter of mercury [mmHg]), diastolic blood pressure (<45 and >100 mmHg) and heart rate (<40 and >110 beats per minute). Only those parameters for which at least one value of PCI was reported are summarized. There were no values of PCI in vital signs parameters over the course of the study.

  • Pharmacokinetic Parameters: Maximum Observed Concentration (Cmax) of GW870086X [ Time Frame: Day 7, 14 and 21 ]
    Cmax was planned to be determined directly from the raw concentration-time data. The pharmacokinetic parameters were planned to be calculated by standard non-compartmental analysis using Win-Nonlin Pro-Version 5.2 or higher.

  • Pharmacokinetic Parameter: Time of Occurrence of Cmax (Tmax) of GW870086 [ Time Frame: Day 7, 14 and 21 ]
    Tmax was planned to be determined directly from the raw concentration-time data. The pharmacokinetic parameters were planned to be calculated by standard non-compartmental analysis using Win-Nonlin Pro-Version 5.2 or higher.

  • Pharmacokintics Parameter: Area Under Curve (AUC) of GW870086 [ Time Frame: Day 7, 14 and 21 ]
    The area under the plasma concentration-time curve to the last quantifiable concentration (AUC[0-t]) and area under the plasma concentration-time curve over the dosing interval (AUC[0-tou]) was planned to be determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The pharmacokinetic parameters were planned to be calculated by standard non-compartmental analysis using Win-Nonlin Pro-Version 5.2 or higher.

  • Pharmacodynamics Endpoint: Skin Thickness and Other Markers of Atopic Dermatitis [ Time Frame: Day 1 and Day 22 ]
    A 4 millimeter (mm) punch skin biopsy was taken pre- and post-treatment (Day 1 and Day 21) from each of the 3 index lesions. The results were not analyzed for this outcome measure.


Enrollment: 25
Study Start Date: December 1, 2010
Study Completion Date: April 14, 2011
Primary Completion Date: March 1, 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GW870086 2.0% &amp; 0.2%
GW870086 2.0%, GW870086 0.2% &amp; Placebo each applied to a separate specific lesion for 21±2 days.
Drug: GW870086 2.0%
White to slightly colored opaque cream
Drug: GW870086 0.2%
White to slightly colored opaque cream
Drug: Placebo
White to slightly colored opaque cream
Experimental: GW870086 2.0% & FP 0.05%
GW870086 2.0%, FP 0.05% &amp; Placebo each applied to a separate specific lesion for 21±2 days.
Drug: GW870086 2.0%
White to slightly colored opaque cream
Drug: FP 0.05%
White cream
Drug: Placebo
White to slightly colored opaque cream
Experimental: GW870086 0.2% & FP 0.05%
GW870086 0.2%, FP 0.05% &amp; Placebo each applied to a separate specific lesion for 21±2 days.
Drug: GW870086 0.2%
White to slightly colored opaque cream
Drug: FP 0.05%
White cream
Drug: Placebo
White to slightly colored opaque cream

Detailed Description:
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. The primary objective of this study is to assess 3 lesions using the Three Item Severity (TIS) score. The secondary objectives are to assess safety and tolerability of GW870086X, assess individual lesions using the Investigators Global Assessment (IGA) and to assess the pharmacokinetics of 21 days dosing of GW870086X administered as a cream. Twenty-five (25) subjects with atopic dermatitis will be randomised to receive placebo and 2 of the following treatments: GW870086X 0.2%, GW870086X 2%, FP 0.05% and placebo. All subjects will receive placebo. Subjects will apply all 3 treatments once daily during the 21 day treatment period. 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 throughout the 21±2 day treatment period. Each index lesion should represent the most common lesions for each patient i.e. not the most or least severe lesions.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01299610


Locations
Germany
GSK Investigational Site
Berlin, Germany, 10117
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 113434
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 113434
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 113434
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 113434
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 113434
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 113434
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 113434
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01299610     History of Changes
Other Study ID Numbers: 113434
First Submitted: February 17, 2011
First Posted: February 18, 2011
Results First Submitted: May 19, 2017
Results First Posted: October 16, 2017
Last Update Posted: November 17, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: http://

Keywords provided by GlaxoSmithKline:
Atopic Dermatitis
GW870086X
TIS
IGA

Additional relevant MeSH terms:
Dermatitis
Dermatitis, Atopic
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases