Clinical trial NCT02637206: Skin Irritation Study of GSK2894512 Cream
Official title: Skin Irritation Study of GSK2894512 Cream-An Evaluator-Blinded Study to Evaluate the Skin Irritation of GSK2894512 Cream and Placebo Following Single Application by Simple-Patch Test and Photo-Patch Test, and Repeat Application Under Non-occlusive Condition in Healthy Japanese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dermatitis, Atopic
Keywords: Healthy Japanese
GSK2894512
skin safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-12-22
Enrollment: 26
Sex: ALL
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: GSK2894512 is a novel anti-inflammatory agent that is currently under development for the topical treatment of atopic dermatitis and chronic plaque psoriasis. This study will be a Phase I, single-center, randomized, partial-blinded (evaluator blinded) study which consists of two parts (Part 1 and 2). Part 1 of this study will assess skin irritation following a single application of GSK2894512 cream at 2 concentrations (e.g. 0.5% and 1%) and placebo by simple-patch test and photo-patch test under semi-occlusive conditions in 20 healthy Japanese volunteers. Part 2 of this study will assess skin irritation following repeat application at 0.5% and 1% of GSK2894512 cream and placebo for 7 days under non-occlusive condition in 6 healthy Japanese volunteers. The study will have Screening visit which will occur within 30 days from the Day 1 visit of each part. Eligible subjects will be able to participate either of Part 1 or Part 2. Subjects will visit the site on Day -1, and hospitalized until the end of all assessments on Day 4 (Part 1) or Day 7 (Part 2). Subjects will re-visit the site on Day 8 (Part 1) or Day 15 (Part 2) for follow-up assessments. This study will be the first to evaluate the safety, tolerability and pharmacokinetics of GSK2894512 cream after single and repeat application in Japanese subjects. Results from this study will enable further clinical investigation in the Japanese population.


Eligibility criteria: 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 tests and 12-lead ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with the GlaxoSmithKline (GSK) Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
* Healthy skin in the potential test site on the back such that erythema and other dermal reactions can be easily visualized.
* Body Mass Index within the range 18.5 - 24.9 kilogram per square meter (kg/m\^2,inclusive) and less than 25.0 kg/m\^2.
* 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 defined as 12 months of spontaneous amenorrhea with simultaneous follicle stimulating hormone (FSH) \> 40 milli-international units per milliliter and estradiol \< 40 picograms per milliliter (\<147 picomole per liter).
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
* Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin \<= 1.5x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Based on single QTc values: QT interval corrected for heart rate according to Fridericia's formula (QTcF) \< 450 milliseconds; QTcF \< 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* History of known or suspected intolerance to any of the ingredients of the study products, adhesive tape/plaster, or the test patches.
* Subjects with inherent sensitivity to sun or history of photosensitivity.
* Inability to evaluate the skin at and around the potential test sites on the back due to sunburns, unevenness in skin tone, tattoos, scars, excessive hair, freckles, birthmarks, moles, or other skin damage or abnormality.
* Clinically-relevant skin disease, including psoriasis, eczema, atopic dermatitis, acne, dysplastic nevi, or other skin pathologies, or a history of skin cancer, that may, in the opinion of the investigator, contraindicate participation or interfere with test site evaluations.
* Considered immunocompromised, or has a clinically-relevant history of or currently suffering from any disease or condition that, in the opinion of the investigator, might affect the evaluation of the study product or place the subject at undue risk.
* A positive pre-study syphilis, Hepatitis B surface antigen, Hepatitis C antibody, Human Immunodeficiency Virus antigen antibody or Human T-cell Lymphotropic Virus-1 result of screening.
* A positive pre-study drug screen.
* The subject has donated a unit of blood "\>400 milliliter (mL)" within the previous 4 months or "\>200 mL" within the previous 1 month prior to the first dosing day.
* The subject has participated in a clinical study with an investigational or a non-investigational drug or device during the previous 4 months prior to the first dosing day.
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* The subject planned to concurrently participate in another clinical study or post-marketing study.
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 14 days prior to the first application of study medication.
* Unwillingness or inability to follow the procedures outlined in the protocol.
* Subject is mentally or legally incapacitated.

Primary outcomes:
measure: Part 1-Positive rate of skin irritability as assessed by simple-patch test following single application of GSK2894512 cream
timeFrame: Up to Day 4
measure: Part 1-Positive rate of photo-urticaria reaction as assessed by photo patch test following single application of GSK2894512 cream
timeFrame: Day 2
measure: Part 1-Positive rate of photo-toxicity as assessed by photo patch test following single application of GSK2894512 cream
timeFrame: Up to Day 4
measure: Part 2- Positive rate of Skin irritability following repeat application of GSK2894512 cream
timeFrame: Day 1 to Day 8
measure: Part 2- Skin observation (subjective symptom)
timeFrame: Day 1 to Day 7
Secondary outcomes:
measure: Part 1: Number of subject with adverse events
timeFrame: From Day 1 to Day 8
measure: Part 2: Number of subject with adverse events
timeFrame: From Day 1 to Day 15
measure: Part 1:Safety as assessed by systolic and diastolic blood pressure measurements
timeFrame: Day -1 to Day 8
measure: Part 2: Safety as assessed by systolic and diastolic blood pressure measurements
timeFrame: Day -1 to Day 15
measure: Part 1:Safety as assessed by pulse rate measurement
timeFrame: Day -1 to Day 8
measure: Part 2: Safety as assessed by pulse rate measurement
timeFrame: Day -1 to Day 15
measure: Part 1:Safety as assessed by12-lead electrocardiogram (ECG)
timeFrame: Day -1 to Day 8
measure: Part 2: Safety as assessed by12-lead ECG
timeFrame: Day -1 to Day 15
measure: Part 1:Safety as assessed by clinical laboratory test
timeFrame: Day -1, 4 and 8
measure: Part 2: Safety as assessed by clinical laboratory test
timeFrame: Day -1, 4, 8 and 15
measure: Part 2: Plasma concentration of GSK2894512
timeFrame: Day 1 and Day 7 (pre-dose, 2, 4 hours post-AM application); Day 3 and Day 5 (pre-dose of AM application)
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: