This study will assess the systemic exposure and pharmacokinetic parameters of GSK2894512 following twice daily topical administration of 1% and 2% cream in adult subjects with AD, and will provide information about the systemic safety as well as local safety and tolerability following twice daily application to up to 35% body surface area (BSA) of affected skin of subjects with AD. It will be an open-label, sequential study consisting of 2 cohorts. A cohort of 6 subjects (Cohort 1) will apply GSK2894512 (cream, 2%) to affected skin on an area ranging from 15 to 35% of the total BSA for 20 days plus a final dose on Day 21. Cohort 2 will consist of 6 subjects that will apply 1% cream. Cohort 2 will follow the same procedures as Cohort 1.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
11
GSK2894512 will be supplied as white to off-white topical cream in doses of 2.0% (20 milligrams/gram \[mg/g\]) and 1.0% (10 mg/g)
GSK Investigational Site
Montreal, Quebec, Canada
Composite of pharmacokinetic (PK) parameters
PK parameters include plasma concentrations of GSK2894512, maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve (AUC) to last measurable concentration \[AUC(0-t)\], AUC through 24 hours \[AUC(0-24)\] and AUC per dosing interval \[AUC(0-tau)\], apparent terminal phase half-life following the last dose (t1/2); steady-state trough concentrations (Ctau), accumulation ratio (Ro), as data allows.
Time frame: On Day 1 at pre-dose, 1 hour (h), 2h, 4h, 8h, 10h, 12h, 14h, 16h; On Days 2, 3, 4, 7 and 14 at Pre-dose; On Day 21 at pre-dose, 1h, 2h, 4h, 8h, 10h, 12h; On Day 22 at 0h
Number of subjects with adverse events (AEs)
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product temporally associated with the use of a medicinal product
Time frame: Up to Day 22
Safety as assessed by Vital signs
Vital signs will include height (only at baseline) and weight (only at baseline and Day 22), temperature, systolic and diastolic blood pressure and pulse rate
Time frame: Up to Day 22
Safety as assessed by electrocardiogram (ECG) parameters
Triplicate 12-lead ECGs will be obtained at each time-point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals.
Time frame: Up to Day 22
Safety as assessed by abbreviated physical examination parameters
Physical examination will include assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
Time frame: Baseline and Day 22
Safety as assessed by clinical laboratory assessments
Clinical laboratory assessments will include hematology, clinical chemistry, urinalysis parameters
Time frame: Baseline, Day 7, 14 and Day 22
Local tolerability as assessed by degree of local irritation
The application sites will be assessed for presence and overall degree of irritation
Time frame: Baseline , Days 1, 2, 3, 4, 7, 14, 21 and 22
Change from baseline in Eczema Area and Severity Index (EASI)
The EASI scoring system is a standard clinical tool for assessing the severity of AD that takes into account the overall severity of erythema, infiltration/papulation, excoriation, and lichenification, as well as the extent of BSA affected with AD.
Time frame: Baseline (Day -1) and Days 3, 7, 14 and 21
Proportion of subjects with >=50% improvement in EASI
Time frame: Baseline (Day -1) and Days 3, 7, 14 and 21
Proportion of subjects who achieve an Investigator's Global Assessment (IGA) of 0 or 1 and have at least a 2-point improvement over baseline
IGA is a clinical tool for assessing the current state/severity of the subject's AD.
Time frame: Baseline (Day -1) and Days 3, 7, 14 and 21
Change from baseline in subject's pruritus (numeric rating scale [NRS])
Subject-reported itch (pruritus) severity will be analyzed by the daily sign and symptom severity diary NRS.
Time frame: Baseline and up to Day 22
Change from baseline in % BSA affected
Percentage of body surface area (BSA) affected will be assessed at the specified time points.
Time frame: Baseline (Day -1) and Days 3, 7, 14 and 21
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