Dermatitis, Atopic
Conditions
Keywords
Atopic Dermatitis, GW870086X, TIS, IGA
Brief summary
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.
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.
Interventions
DRUGGW870086 2.0%
White to slightly colored opaque cream
DRUGGW870086 0.2%
White to slightly colored opaque cream
DRUGFP 0.05%
White cream
DRUGPlacebo
White to slightly colored opaque cream
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Three Item Severity (TIS) Scores Between GW870086 (0.2% and 2%) Versus Placebo at Day 22 | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | 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) | 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) | 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 | 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. |
| Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | 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. |
| Pharmacokinetic Parameters: Maximum Observed Concentration (Cmax) of GW870086X | 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 | 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 | 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 | 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. |
| Number of Participants With Abnormal Vital Signs (Systolic and Diastolic Blood Pressure and Pulse Rate) of PCI | 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. |
Countries
Germany
Participant flow
Recruitment details
The study was conducted at one center in Germany between 13 December 2010 and 14 April 2011.
Pre-assignment details
Twenty five participants were randomized and completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Treatment 1: GW870086, 2.0%, GW870086, 0.2% and Placebo Participants applied GW870086, 2.0% cream, GW870086, 0.2% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and the study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of the pots, the use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. The participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20. | 10 |
| Treatment 2: GW870086 2.0%, FP 0.05% and Placebo Participants applied GW870086, 2.0% cream, Fluticasone Propionate (FP) 0.05% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20. | 5 |
| Treatment 3: GW870086 0.2%, FP 0.05% and Placebo Participants applied GW870086, 0.2% cream, FP, 0.05% cream and placebo cream to a separate specific lesion located on the arms and/or legs (one lesion per limb), applying same study treatment to the same lesion every day for 21±2 days. For first three days of the study, participants applied their randomly assigned treatments at the same time of day during the clinic visits and study personnel supervised to ensure that the correct application procedures were followed. A full explanation was given to each participant regarding the labeling of pots, use of disposable gloves, the volume of cream to be used for each single application and the size of the area of skin to be treated. Participants applied their study treatments under supervision at the clinic on Days 7, 14 and 21 to allow accurately timed pharmacokinetic blood sampling and assessment of local tolerability. Participants applied their treatments at home on Day 4 to 6, Day 8 to 13 and Day 15 to 20. | 10 |
| Total | 25 |
Baseline characteristics
| Characteristic | Treatment 1: GW870086, 2.0%, GW870086, 0.2% and Placebo | Treatment 2: GW870086 2.0%, FP 0.05% and Placebo | Treatment 3: GW870086 0.2%, FP 0.05% and Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 41.9 Years STANDARD_DEVIATION 18.81 | 40.8 Years STANDARD_DEVIATION 19.43 | 28.3 Years STANDARD_DEVIATION 10.15 | 36.2 Years STANDARD_DEVIATION 16.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 5 Participants | 10 Participants | 25 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 9 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 10 | 2 / 5 | 5 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 | 0 / 10 |
Outcome results
Primary
Change From Baseline Three Item Severity (TIS) Scores Between GW870086 (0.2% and 2%) Versus Placebo at 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.
Time frame: Baseline (Day 1) and Day 22
Population: The Efficacy Population was defined as participants in the 'All Subjects' population with at least one post dose TIS assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GW870086, 0.2% Cream | Change From Baseline Three Item Severity (TIS) Scores Between GW870086 (0.2% and 2%) Versus Placebo at Day 22 | -1.99 Score on scale | Standard Error 0.418 |
| GW870086, 2.0% Cream | Change From Baseline Three Item Severity (TIS) Scores Between GW870086 (0.2% and 2%) Versus Placebo at Day 22 | -2.49 Score on scale | Standard Error 0.465 |
| Placebo | Change From Baseline Three Item Severity (TIS) Scores Between GW870086 (0.2% and 2%) Versus Placebo at Day 22 | -1.61 Score on scale | Standard Error 0.38 |
| FP, 0.05% Cream | Change From Baseline Three Item Severity (TIS) Scores Between GW870086 (0.2% and 2%) Versus Placebo at Day 22 | -3.11 Score on scale | Standard Error 0.467 |
p-value: 0.4895% CI: [-1.46, 0.7]Mixed model for repeated measures
p-value: 0.11895% CI: [-2, 0.23]Mixed model for repeated measures
p-value: 0.01195% CI: [-2.65, -0.36]Mixed model for repeated measures
Secondary
Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on 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.
Time frame: Days 2, 3, 7, and 14
Population: Efficacy Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GW870086, 0.2% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 7 | -1.43 Score on scale | Standard Error 0.363 |
| GW870086, 0.2% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 2 | -0.37 Score on scale | Standard Error 0.19 |
| GW870086, 0.2% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 3 | -0.91 Score on scale | Standard Error 0.266 |
| GW870086, 0.2% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 14 | -1.82 Score on scale | Standard Error 0.367 |
| GW870086, 2.0% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 2 | -0.53 Score on scale | Standard Error 0.203 |
| GW870086, 2.0% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 14 | -2.23 Score on scale | Standard Error 0.408 |
| GW870086, 2.0% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 3 | -0.80 Score on scale | Standard Error 0.291 |
| GW870086, 2.0% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 7 | -1.78 Score on scale | Standard Error 0.403 |
| Placebo | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 2 | -0.45 Score on scale | Standard Error 0.181 |
| Placebo | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 7 | -1.19 Score on scale | Standard Error 0.331 |
| Placebo | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 14 | -1.58 Score on scale | Standard Error 0.335 |
| Placebo | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 3 | -0.94 Score on scale | Standard Error 0.246 |
| FP, 0.05% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 14 | -2.97 Score on scale | Standard Error 0.409 |
| FP, 0.05% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 2 | -0.62 Score on scale | Standard Error 0.203 |
| FP, 0.05% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 3 | -1.22 Score on scale | Standard Error 0.292 |
| FP, 0.05% Cream | Change From Baseline TIS Scores Between GW870086X (0.2% and 2%) Versus Placebo on Days 2, 3, 7 and 14 | Day 7 | -2.47 Score on scale | Standard Error 0.405 |
Comparison: GW870086, 0.2% cream Vs Placebo: Day 2p-value: 0.58195% CI: [-0.24, 0.42]Mixed model repeated measures
Comparison: GW870086, 2.0% cream Vs Placebo: Day 2p-value: 0.65595% CI: [-0.42, 0.27]Mixed model repeated measures
Comparison: FP, 0.05% cream Vs Placebo: Day 2p-value: 0.33695% CI: [-0.52, 0.18]Mixed model repeated measures
Comparison: GW870086 0.2% cream Vs Placebo: Day 3p-value: 0.92395% CI: [-0.58, 0.63]Mixed model repeated measures
Comparison: GW870086, 2.0% cream, Placebo: Day 3p-value: 0.65795% CI: [-0.49, 0.77]Mixed model repeated measures
Comparison: Placebo, FP, 0.05% cream: Day 3p-value: 0.38695% CI: [-0.93, 0.36]Mixed model repeated measures
Comparison: GW870086, 0.2% cream, Placebo: Day 7p-value: 0.60195% CI: [-1.15, 0.67]Mixed model repeated measures
Comparison: GW870086, 2.0% cream, Placebo: Day 7p-value: 0.21295% CI: [-1.54, 0.35]Mixed model repeated measures
Comparison: Placebo, FP, 0.05% cream: Day 7p-value: 0.0195% CI: [-2.26, -0.32]Mixed model repeated measures
Comparison: GW870086, 0.2% cream, Placebo: Day 14p-value: 0.60295% CI: [-1.17, 0.68]Mixed model repeated measures
Comparison: GW870086, 2.0% cream, Placebo: Day 14p-value: 0.1895% CI: [-1.61, 0.31]Mixed model repeated measures
Comparison: Placebo, FP, 0.05% cream: Day 14p-value: 0.00695% CI: [-2.37, -0.4]Mixed model repeated measures
Secondary
Number of Investigators Global Assessment (IGA) Responders on 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.
Time frame: Days 2, 3, 7, 14 and 22
Population: Efficacy population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GW870086, 0.2% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 3 | 0 Participants |
| GW870086, 0.2% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 2 | 0 Participants |
| GW870086, 0.2% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 7 | 3 Participants |
| GW870086, 0.2% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 14 | 8 Participants |
| GW870086, 0.2% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 22 | 6 Participants |
| GW870086, 2.0% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 3 | 0 Participants |
| GW870086, 2.0% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 7 | 1 Participants |
| GW870086, 2.0% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 2 | 0 Participants |
| GW870086, 2.0% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 22 | 4 Participants |
| GW870086, 2.0% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 14 | 2 Participants |
| Placebo | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 7 | 1 Participants |
| Placebo | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 3 | 1 Participants |
| Placebo | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 22 | 7 Participants |
| Placebo | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 2 | 1 Participants |
| Placebo | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 14 | 4 Participants |
| FP, 0.05% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 2 | 2 Participants |
| FP, 0.05% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 7 | 6 Participants |
| FP, 0.05% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 22 | 11 Participants |
| FP, 0.05% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 14 | 6 Participants |
| FP, 0.05% Cream | Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22 | Day 3 | 1 Participants |
Secondary
Number of Participants With Abnormal Electrocardiogram (ECG) of PCI
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.
Time frame: Up to Day 21
Population: All subject population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GW870086, 0.2% Cream | Number of Participants With Abnormal Electrocardiogram (ECG) of PCI | 1 Participants |
| GW870086, 2.0% Cream | Number of Participants With Abnormal Electrocardiogram (ECG) of PCI | 1 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) of PCI | 1 Participants |
Secondary
Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI)
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.
Time frame: Up to Day 21
Population: All subject population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GW870086, 0.2% Cream | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose, Low | 0 Participants |
| GW870086, 0.2% Cream | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Lymphocyte, Low | 1 Participants |
| GW870086, 0.2% Cream | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST, High | 0 Participants |
| GW870086, 0.2% Cream | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total Neutrophils, Low | 1 Participants |
| GW870086, 2.0% Cream | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST, High | 0 Participants |
| GW870086, 2.0% Cream | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose, Low | 0 Participants |
| GW870086, 2.0% Cream | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total Neutrophils, Low | 0 Participants |
| GW870086, 2.0% Cream | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Lymphocyte, Low | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose, Low | 1 Participants |
| Placebo | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total Neutrophils, Low | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST, High | 1 Participants |
| Placebo | Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Lymphocyte, Low | 1 Participants |
Secondary
Number of Participants With Abnormal Vital Signs (Systolic and Diastolic Blood Pressure and Pulse Rate) of PCI
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.
Time frame: Up to Day 21
Population: All subject population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GW870086, 0.2% Cream | Number of Participants With Abnormal Vital Signs (Systolic and Diastolic Blood Pressure and Pulse Rate) of PCI | 0 Participants |
| GW870086, 2.0% Cream | Number of Participants With Abnormal Vital Signs (Systolic and Diastolic Blood Pressure and Pulse Rate) of PCI | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs (Systolic and Diastolic Blood Pressure and Pulse Rate) of PCI | 0 Participants |
Secondary
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Upto Day 21
Population: All Subjects Population was defined as all participants who had at least one application of placebo, GW870086X 0.2%, GW 870086X 2% or FP 0.05% cream.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GW870086, 0.2% Cream | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 6 Participants |
| GW870086, 0.2% Cream | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| GW870086, 2.0% Cream | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 2 Participants |
| GW870086, 2.0% Cream | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| Placebo | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| Placebo | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 5 Participants |
Secondary
Pharmacodynamics Endpoint: Skin Thickness and Other Markers of Atopic Dermatitis
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.
Time frame: Day 1 and Day 22
Population: Efficacy Population
Secondary
Pharmacokinetic Parameters: Maximum Observed Concentration (Cmax) of GW870086X
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.
Time frame: Day 7, 14 and 21
Population: Pharmacokinetic population was defined as participants in the All Subjects population for whom a pharmacokinetic sample was obtained and analyzed. Cmax was not analysed because the plasma concentrations were not quantifiable.
Secondary
Pharmacokinetic Parameter: Time of Occurrence of Cmax (Tmax) of GW870086
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.
Time frame: Day 7, 14 and 21
Population: Pharmacokinetics population. Tmax was not analysed because the plasma concentrations were not quantifiable.
Secondary
Pharmacokintics Parameter: Area Under Curve (AUC) of GW870086
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.
Time frame: Day 7, 14 and 21
Population: Pharmacokinetics population. AUC was not analyzed because the plasma concentrations were not quantifiable.