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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GW870086 2.0% & 0.2% | Experimental | GW870086 2.0%, GW870086 0.2% & Placebo each applied to a separate specific lesion for 21±2 days. |
|
| GW870086 2.0% & FP 0.05% | Experimental | GW870086 2.0%, FP 0.05% & Placebo each applied to a separate specific lesion for 21±2 days. |
|
| GW870086 0.2% & FP 0.05% | Experimental | GW870086 0.2%, FP 0.05% & Placebo each applied to a separate specific lesion for 21±2 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GW870086 2.0% | Drug | White to slightly colored opaque cream |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline (Day 1) and Day 22 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Berlin | 10117 | Germany |
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| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 113434 | Statistical Analysis Plan | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Twenty five participants were randomized and completed the study.
The study was conducted at one center in Germany between 13 December 2010 and 14 April 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The Efficacy Population was defined as participants in the 'All Subjects' population with at least one post dose TIS assessment. | Posted | Least Squares Mean | Standard Error | Score on scale | Baseline (Day 1) and Day 22 |
AEs were collected from the start of study treatment (Day 1) and until the follow-up contact (approximately 7-14 days after last dose).
All Subjects Population
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003872 | Dermatitis |
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| GW870086 0.2% | Drug | White to slightly colored opaque cream |
|
| FP 0.05% | Drug | White cream |
|
| Placebo | Drug | White to slightly colored opaque cream |
|
| Days 2, 3, 7, and 14 |
| 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. | Days 2, 3, 7, 14 and 22 |
| 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. | Upto Day 21 |
| 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. | Up to Day 21 |
| 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. | Up to Day 21 |
| 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. | Up to Day 21 |
| 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. | Day 7, 14 and 21 |
| 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. | Day 7, 14 and 21 |
| 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. | Day 7, 14 and 21 |
| 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. | Day 1 and Day 22 |
For additional information about this study please refer to the GSK Clinical Study Register |
| 113434 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113434 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113434 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113434 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113434 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113434 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | GW870086, 0.2% Cream | Participants applied GW870086, 0.2% cream to a specific lesion located on the arms and/or legs 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. |
| OG001 | GW870086, 2.0% Cream | Eligible participants applied GW870086, 2.0% cream to a specific lesion located on the arms and/or legs 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. |
| OG002 | Placebo | Eligible participants applied matching placebo to a specific lesion located on the arms and/or legs 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. |
| OG003 | FP, 0.05% Cream | Eligible participants applied FP, 0.05% cream to a specific lesion located on the arms and/or legs 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. |
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| 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. | Efficacy Population | Posted | Least Squares Mean | Standard Error | Score on scale | Days 2, 3, 7, and 14 |
|
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| 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. | Efficacy population | Posted | Count of Participants | Participants | Days 2, 3, 7, 14 and 22 |
|
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| 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. | 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. | Posted | Count of Participants | Participants | Upto Day 21 |
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| 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. | All subject population | Posted | Count of Participants | Participants | Up to Day 21 |
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| 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. | All subject population | Posted | Count of Participants | Participants | Up to Day 21 |
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| 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. | All subject population | Posted | Count of Participants | Participants | Up to Day 21 |
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| 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. | 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. | Posted | Day 7, 14 and 21 |
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|
| 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. | Pharmacokinetics population. Tmax was not analysed because the plasma concentrations were not quantifiable. | Posted | Day 7, 14 and 21 |
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| 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. | Pharmacokinetics population. AUC was not analyzed because the plasma concentrations were not quantifiable. | Posted | Day 7, 14 and 21 |
|
|
| 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. | Efficacy Population | Posted | Day 1 and Day 22 |
|
|
| 0 |
| 10 |
| 6 |
| 10 |
| EG001 | 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. | 0 | 5 | 2 | 5 |
| EG002 | 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. | 0 | 10 | 5 | 10 |
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Gastroenteritis norovirus | Infections and infestations | MedDRA | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Day 3 |
|
| Day 7 |
|
| Day 14 |
|
| Mixed model repeated measures |
| 0.655 |
| Difference in Adjusted Means |
| -0.08 |
| Standard Error of the Mean |
| 0.169 |
| 2-Sided |
| 95 |
| -0.42 |
| 0.27 |
| Superiority or Other |
| FP, 0.05% cream Vs Placebo: Day 2 | Mixed model repeated measures | 0.336 | Difference in Adjusted Means | -0.17 | Standard Error of the Mean | 0.174 | 95 | -0.52 | 0.18 | Superiority or Other |
| GW870086 0.2% cream Vs Placebo: Day 3 | Mixed model repeated measures | 0.923 | Difference in Adjusted Means | 0.03 | Standard Error of the Mean | 0.302 | 2-Sided | 95 | -0.58 | 0.63 | Superiority or Other |
| GW870086, 2.0% cream, Placebo: Day 3 | Mixed model repeated measures | 0.657 | Difference in Adjusted Means | 0.14 | Standard Error of the Mean | 0.314 | 2-Sided | 95 | -0.49 | 0.77 | Superiority or Other |
| Placebo, FP, 0.05% cream: Day 3 | Mixed model repeated measures | 0.386 | Difference in Adjusted Means | -0.28 | Standard Error of the Mean | 0.323 | 2-Sided | 95 | -0.93 | 0.36 | Superiority or Other |
| GW870086, 0.2% cream, Placebo: Day 7 | Mixed model repeated measures | 0.601 | Difference in Adjusted Means | -0.24 | Standard Error of the Mean | 0.456 | 2-Sided | 95 | -1.15 | 0.67 | Superiority or Other |
| GW870086, 2.0% cream, Placebo: Day 7 | Mixed model repeated measures | 0.212 | Difference in Adjusted Means | -0.60 | Standard Error of the Mean | 0.472 | 2-Sided | 95 | -1.54 | 0.35 | Superiority or Other |
| Placebo, FP, 0.05% cream: Day 7 | Mixed model repeated measures | 0.010 | Difference in Adjusted Means | -1.29 | Standard Error of the Mean | 0.485 | 2-Sided | 95 | -2.26 | -0.32 | Superiority or Other |
| GW870086, 0.2% cream, Placebo: Day 14 | Mixed model repeated measures | 0.602 | Difference in Adjusted Means | -0.24 | Standard Error of the Mean | 0.462 | 2-Sided | 95 | -1.17 | 0.68 | Superiority or Other |
| GW870086, 2.0% cream, Placebo: Day 14 | Mixed model repeated measures | 0.180 | Difference in Adjusted Means | -0.65 | Standard Error of the Mean | 0.479 | 2-Sided | 95 | -1.61 | 0.31 | Superiority or Other |
| Placebo, FP, 0.05% cream: Day 14 | Mixed model repeated measures | 0.006 | Difference in Adjusted Means | -1.39 | Standard Error of the Mean | 0.492 | 2-Sided | 95 | -2.37 | -0.40 | Superiority or Other |
| Day 3 |
|
| Day 7 |
|
| Day 14 |
|
| Day 22 |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| AST, High |
|
| Glucose, Low |
|