Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GSK2894512 Topical Cream, GSK2894512 Cream
GSK2894512 · 3 trials · 2 indications
It is the sum of dermal response irritation scores from Day 2 through Day 22 divided by the number of non-missing observations
It is the sum of dermal response irritation scores from Day 2 through Day 22
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 |
|---|---|---|
| GSK2894512 0.5% | EXPERIMENTAL | Each subject will receive a topical application of GSK2894512 0.5% under semi-occlusive patch conditions once daily (OD) for 21 days. |
| GSK2894512 1% | EXPERIMENTAL | Each subject will receive a topical application of GSK2894512 1% under semi- occlusive patch conditions OD for 21 days. |
| GSK2894512 2% | EXPERIMENTAL | Each subject will receive a topical application of GSK2894512 2% under semi-occlusive patch conditions OD for 21 days. |
| Vehicle | PLACEBO_COMPARATOR | Each subject will receive a topical application of Vehicle cream under semi-occlusive patch conditions OD for 21 days. |
| Sodium lauryl sulfate 0.1% | ACTIVE_COMPARATOR | Each subject will receive a topical application of 0.2 milliliter (mL) of Sodium lauryl sulfate under semi-occlusive patch conditions OD for 21 days. This will serve as a positive control. |
| Petrolatum | ACTIVE_COMPARATOR | Each subject will receive a topical application of 0.2 mL of Petrolatum under semi-occlusive patch conditions OD for 21 days. This will serve as a negative control. |
| 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 is a white to off-white cream that will be applied topically in 3 different concentrations (0.5% \[5 milligram (mg)/gram (g)\], 1% \[10 mg/g\], and 2% \[20 mg/g\]). |
| Vehicle cream | DRUG | Vehicle cream does not contain any active pharmaceutical ingredient. |
| Positive control | DRUG | Positive control contains sodium lauryl sulfate solution 0.1% (1 mg/g). |
| Negative control | DRUG | Negative control contains petrolatum. |
| 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: * Aged 18 to 65 years, inclusive, at time of consent. * In generally good overall health with healthy skin in the potential test sites on the back. * Skin tone in the potential test sites on the back such that erythema and other dermal reactions can be easily visualized, i.e., F...
GSK2894512 is an investigational small molecule developed by GSK plc as a topical cream for dermatological conditions. It is being studied in atopic dermatitis and psoriasis. GSK2894512 is in Phase 1 clinical development and has not been approved for any indication.
GSK2894512 is being evaluated as a topical treatment for atopic dermatitis. Clinical trials have studied its pharmacokinetics and skin irritation potential in adults with atopic dermatitis. It remains investigational and is not approved for use in atopic dermatitis or any other condition.
GSK2894512 is developed by GSK plc, which trades under the ticker GSK. The company is the sponsor of the clinical trials evaluating this topical cream in atopic dermatitis and psoriasis.
GSK2894512 is in Phase 1 clinical development. It is an investigational product and has not received FDA approval. All completed trials to date have been Phase 1 studies.
GSK2894512 has been studied in three completed Phase 1 trials: NCT02637206, a skin irritation study in Japan; NCT02466152, a pharmacokinetic study in Canada; and NCT01984775, an irritation potential study in the United States and Germany. No trials are currently active.
Yes, GSK2894512 Topical Cream and GSK2894512 Cream are alternative names for GSK2894512. They refer to the same investigational small molecule formulated as a topical cream for atopic dermatitis and psoriasis.