Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02637206 | Skin Irritation Study of GSK2894512 Cream | PHASE1 | COMPLETED | 26 | — | — | Oct 27, 2015 | Dec 2, 2015 | Jul 18, 2017 | 1 | Japan |
| NCT02466152 | Pharmacokinetic Study of Topical GSK2894512 Cream | PHASE1 | COMPLETED | 11 | — | — | May 28, 2015 | Oct 27, 2015 | May 9, 2017 | 1 | Canada |
Each test site for the simple-patch test will be evaluated at 30 minutes (min) and 24 hours (hrs) after removal of medication (48.5 hr and 72 hrs after application, respectively) based on the following criteria proposed by the patch test study group in Japan: no reaction (-); weak erythema (+-); erythema (+); erythema + edema (++); erythema + edema + papules, or vesicles (+++); bullae (++++). Except no reaction (-) and weak erythema (+-), rest all findings from simple-patch test will be considered as positive.
For the photo-patch test, 4 test patches (right back) will be removed 24 hrs after application and the test sites will be exposed to 6.0 joule per square centimeter of ultraviolet A. Each test site will be evaluated at 30 minutes from the irradiation to determine whether there is photo-urticaria or not (i.e positive or negative).
Post photo-urticaria evaluation, the test sites will be re-covered with empty patches, that will be removed at 24 hrs after removal of medication. The test sites will be evaluated at 30 min and 24 hrs after empty patches removal (48.5 and 72 hrs after application, respectively). Assessment Criteria includes: no reaction or similar to the non irradiation site (-); Slightly stronger than the non irradiation site (+-);Definitely stronger than the non irradiation site (+); 2 ranks stronger than the non irradiation site according to the criteria in Japan (++); 3 ranks stronger than the non irradiation site according to the criteria in Japan (+++). Test results of more than or equal to +- will be considered as positive.
Each test site will be evaluated at 30 min after removal of medication based on the following criteria proposed by the patch test study group in Japan: no reaction (-); weak erythema (+-); erythema (+); erythema + edema (++); erythema + edema + papules, or vesicles (+++); bullae (++++). Except no reaction (-) and weak erythema (+-), rest all findings from simple-patch test will be considered as positive.
At each application site 2 hours following application of study drugs, skin observation (subjective symptom) from application to judgement (2 hours) will be heard from subjects. Symptoms will be recorded as a score ranging from 0-4, where 0=Normal, no discomfort; 1=an awareness, but no discomfort and no intervention required; 2=a noticeable discomfort that causes intermittent awareness; 3=a noticeable discomfort that causes intermittent awareness and interferes occasionally with normal daily activities; 4=a definite continuous discomfort that interferes with normal daily activities.
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.
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
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
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.
Physical examination will include assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
Clinical laboratory assessments will include hematology, clinical chemistry, urinalysis parameters
The application sites will be assessed for presence and overall degree of irritation
| Arm | Type | Description |
|---|---|---|
| Part 1 (Single Application) | EXPERIMENTAL | All subjects will have two sets (left and right) of 4 semi-occlusive test patches applied to randomized test sites on their upper backs on Day 1. Test patches on left back will be for simple-patch test and those on right back will be for photo-patch test. Each set will consist of approximately 150 micro liter (0.15 mL) of the following study treatments: GSK2894512 0.5% cream, GSK2894512 1% cream, placebo (cream vehicle without the active ingredient) and an empty patch. The test patches will be applied for 24 hrs (photo-patch test) or 48 hrs (simple-patch test). |
| Part 2 (Repeat Application) | EXPERIMENTAL | All subjects will have repeat applications of GSK2894512 0.5%, 1% cream and placebo twice a day for 7 days on both side (left and right, 3 in total) of their upper back (approximately 5 centimeter (cm) in diameter \>10 cm away from another application area) under non-occlusive conditions and covered with gauze using adhesive. GSK2894512 0.5% and 1% cream and placebo will be randomized according to the randomization code in the same manner as Part 1. |
| GSK2894512 2.0% Cohort | EXPERIMENTAL | Subjects will apply a thin layer of GSK2894512 2.0% topical cream twice daily (morning and evening) for 20 days and only in morning on day 21, to all affected skin areas (15-35% BSA) identified at baseline, excluding the scalp and around the eyes |
| GSK2894512 1.0% Cohort | EXPERIMENTAL | Subjects will apply a thin layer of GSK2894512 1.0% topical cream twice daily (morning and evening) for 20 days and only in morning on day 21, to all affected skin areas (15-35% BSA) identified at baseline, excluding the scalp and around the eyes |
| Name | Type | Description |
|---|---|---|
| GSK2894512 Cream | DRUG | GSK2894512 cream supplied will be white to off-white cream packaged in 28-gram laminate tubes of 2 concentrations: 0.5% and 1%, to be applied topically. |
| Vehicle Cream | DRUG | Vehicle Cream (placebo cream without active ingredient) supplied will be white to off-white cream packaged in 28-gram laminate tubes, to be applied topically. |
| Empty Patch | DRUG | Empty patches without any ingredients will be used as negative control. |
| GSK2894512 Topical Cream | DRUG | 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) |
Inclusion Criteria: * Japanese males and females aged between 20 and 64 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory ...