A Randomised, Double-blind, Placebo-controlled Study of Topical GW870086X Formulation in Subjects With Moderate or Severe Atopic Dermatitis
Overview
- Phase
- Phase 2
- Intervention
- GW870086 2.0%
- Conditions
- Dermatitis, Atopic
- Sponsor
- GlaxoSmithKline
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Change From Baseline Three Item Severity (TIS) Scores Between GW870086 (0.2% and 2%) Versus Placebo at Day 22
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility 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.
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.
Arms & Interventions
GW870086 2.0% & 0.2%
GW870086 2.0%, GW870086 0.2% \& Placebo each applied to a separate specific lesion for 21±2 days.
Intervention: GW870086 2.0%
GW870086 2.0% & 0.2%
GW870086 2.0%, GW870086 0.2% \& Placebo each applied to a separate specific lesion for 21±2 days.
Intervention: GW870086 0.2%
GW870086 2.0% & 0.2%
GW870086 2.0%, GW870086 0.2% \& Placebo each applied to a separate specific lesion for 21±2 days.
Intervention: Placebo
GW870086 2.0% & FP 0.05%
GW870086 2.0%, FP 0.05% \& Placebo each applied to a separate specific lesion for 21±2 days.
Intervention: GW870086 2.0%
GW870086 2.0% & FP 0.05%
GW870086 2.0%, FP 0.05% \& Placebo each applied to a separate specific lesion for 21±2 days.
Intervention: FP 0.05%
GW870086 2.0% & FP 0.05%
GW870086 2.0%, FP 0.05% \& Placebo each applied to a separate specific lesion for 21±2 days.
Intervention: Placebo
GW870086 0.2% & FP 0.05%
GW870086 0.2%, FP 0.05% \& Placebo each applied to a separate specific lesion for 21±2 days.
Intervention: GW870086 0.2%
GW870086 0.2% & FP 0.05%
GW870086 0.2%, FP 0.05% \& Placebo each applied to a separate specific lesion for 21±2 days.
Intervention: FP 0.05%
GW870086 0.2% & FP 0.05%
GW870086 0.2%, FP 0.05% \& Placebo each applied to a separate specific lesion for 21±2 days.
Intervention: Placebo
Outcomes
Primary Outcomes
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 Outcomes
- 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)
- Number of Investigators Global Assessment (IGA) Responders on Days 2, 3, 7, 14 and 22(Days 2, 3, 7, 14 and 22)
- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)(Upto Day 21)
- Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Importance (PCI)(Up to Day 21)
- Number of Participants With Abnormal Electrocardiogram (ECG) of PCI(Up to Day 21)
- Number of Participants With Abnormal Vital Signs (Systolic and Diastolic Blood Pressure and Pulse Rate) of PCI(Up to Day 21)
- Pharmacodynamics Endpoint: Skin Thickness and Other Markers of Atopic Dermatitis(Day 1 and Day 22)
- Pharmacokinetic Parameters: Maximum Observed Concentration (Cmax) of GW870086X(Day 7, 14 and 21)
- Pharmacokinetic Parameter: Time of Occurrence of Cmax (Tmax) of GW870086(Day 7, 14 and 21)
- Pharmacokintics Parameter: Area Under Curve (AUC) of GW870086(Day 7, 14 and 21)