A Randomized, Single-Blind, Dose-Rising Study to Evaluate the Safety, Tolerability and Preliminary Pharmacokinetics of Single and 14 Day Repeat Topical Applications of GSK1940029 Gel on the Intact Skin of Healthy Human Subjects
Overview
- Phase
- Phase 1
- Intervention
- 0.3% GSK1940029 gel
- Conditions
- Acne Vulgaris
- Sponsor
- GlaxoSmithKline
- Enrollment
- 55
- Locations
- 1
- Primary Endpoint
- Safety of GSK1940029 as assessed by physical examination findings.
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The proposed indication for GSK1940029 is topical treatment of acne, the early clinical plan will evaluate the irritation potential of GSK1940029 (Study SCD117225 - 3 Part study); and safety, tolerability and pharmacokinetics of GSK1940029 (Study SCD117226 - 2 Part study), after topical administration on healthy subjects and acne patients. Study SCD117226 will be a randomized, single-blind, dose-rising study to evaluate the safety, tolerability and preliminary pharmacokinetics of single and 14 day repeat topical applications of GSK1940029 gel on the intact skin of healthy human subjects. Part 1: (single-dose) subjects will receive 0.3% or 1% GSK1940029 (or matching vehicle), as a single approximately (App) 24 hour (h) (22.5h) application to a surface area of 400 square centimeter (cm^2) (0.3%), 400 cm^2 (1%) or 1200 cm^2 (1%), respectively, in each of three sequential cohorts. Part 2: (repeat-dose) subjects will receive 0.3% or 1% GSK1940029 (or matching vehicle), as 14 daily App24h (22.5h) application to a surface area of 400 cm^2 (0.3%), 400 cm^2 (1%) or 1200 cm^2 (1%), respectively, in each of three sequential cohorts. Parts within Study SCD117225 and Study SCD117226 will have interdependencies. No significant primary irritation signal in Study SCD117225 Part 1 (primary irritation) would allow initiation of Study SCD117226 Part 1. Once safety, tolerability and exposure information are determined in Study SCD117226 Part 1, then Part 2 (cumulative irritation) of Study SCD117225 may be initiated along with Part 2 of Study SCD117226. No significant cumulative irritation signal (study SCD117225 Part 2) in combination with adequate 14-day safety (study SCD117226 Part 2) would allow initiation of Part 3 (facial irritation) of Study SCD117225.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- •A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- •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 (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] \>40 milli international units MIU/ milliliter (mL) and estradiol \< 40 picograms (pg)/mL (\<147 picomole \[pmol\]/liter \[L\]) is confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will not be allowed.
- •Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the Protocol. This criterion must be followed from the time of the first dose of study medication until after study follow-up visit.
- •Alanine amino transfrase, alkaline phosphatase and bilirubin \<=1.5 x ULN (upper limit of normal) (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
- •Based on single or averaged assessments, corrected QT interval (QTc) \< 450 milliseconds (msec); or QTc \<480 msec in subjects with Bundle Branch Block.
Exclusion Criteria
- •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome). Subjects with a history of gall stones, asymptomatic gallstones or cholecystectomy will be excluded.
- •A positive pre-study drug/alcohol screen.
- •A positive test for Human Immunodeficiency virus HIV antibody.
- •History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>14 standard drinks. One standard drink is equivalent to 10 gram of alcohol: 285 mL of beer, 100 mL of wine or 30 mL of 40% alcohol by volume distilled spirits.
- •History of or current meibomian gland dysfunction or dry eye disease
- •History or presence of significant skin disorder (such as but not limited to severe (extensive) atopic dermatitis, severe eczema, psoriasis or skin cancer) that would in any way confound interpretation of the study results, or subjects who present with damaged skin including sunburn, moles, uneven skin tones, scar tissue, tattoos, body piercings, sunburn, branding or other disfiguration on or near the intended site of application which could interfere with the grading.
- •History of cutaneous photodisorder, such as photoallergic reaction or polymorphic light eruption. - History of cold urticaria and reactions to extreme temperatures.
- •History of allergy to soaps, lotions, cosmetics, tape/adhesives, petrolatum or latex or topical drugs of same class as the study medication.
- •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
Arms & Interventions
Part 1
Subjects will receive 0.3% or 1% GSK1940029 (or matching vehicle), as a single App 24h (22.5h) application to 400 cm\^2 (0.3%), 400 cm\^2 (1%) or 1200 cm\^2 (1%), respectively, in each of three sequential cohorts
Intervention: 0.3% GSK1940029 gel
Part 1
Subjects will receive 0.3% or 1% GSK1940029 (or matching vehicle), as a single App 24h (22.5h) application to 400 cm\^2 (0.3%), 400 cm\^2 (1%) or 1200 cm\^2 (1%), respectively, in each of three sequential cohorts
Intervention: 1% GSK1940029 gel
Part 1
Subjects will receive 0.3% or 1% GSK1940029 (or matching vehicle), as a single App 24h (22.5h) application to 400 cm\^2 (0.3%), 400 cm\^2 (1%) or 1200 cm\^2 (1%), respectively, in each of three sequential cohorts
Intervention: 0.3%/1% vehicle gel only
Part 2
Subjects will receive 0.3% or 1% GSK1940029 (or matching vehicle), as 14 daily App24h (22.5h) application to 400 cm\^2 (0.3%), 400 cm\^2 (1%) or 1200 cm\^2 (1%), respectively, in each of three sequential cohorts
Intervention: 0.3% GSK1940029 gel
Part 2
Subjects will receive 0.3% or 1% GSK1940029 (or matching vehicle), as 14 daily App24h (22.5h) application to 400 cm\^2 (0.3%), 400 cm\^2 (1%) or 1200 cm\^2 (1%), respectively, in each of three sequential cohorts
Intervention: 1% GSK1940029 gel
Part 2
Subjects will receive 0.3% or 1% GSK1940029 (or matching vehicle), as 14 daily App24h (22.5h) application to 400 cm\^2 (0.3%), 400 cm\^2 (1%) or 1200 cm\^2 (1%), respectively, in each of three sequential cohorts
Intervention: 0.3%/1% vehicle gel only
Outcomes
Primary Outcomes
Safety of GSK1940029 as assessed by physical examination findings.
Time Frame: Screening, Day -1, and follow-up (FU) (Days 6 to 8) of Part 1; Screening, Day -1, and FU (Days 20 to 22) of Part 2
Complete physical examination will include assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities
Safety of GSK1940029 as assessed by vital signs
Time Frame: Screening, Days 1, 2 and FU (Days 6 to 8) of Part 1; Screening, Days 1, 2, 7 14, and FU (Days 20 to 22) of Part 2
Vital signs measurements will include systolic and diastolic blood pressure, heart rate and temperature
Safety of GSK1940029 as assessed by 12-lead electrocardiogram (ECG)
Time Frame: Screening, Day 1 and Day 2 of Part 1; Screening, Day 1, 2, 7, 12, 13 and 14 of Part 2
Single 12-lead ECG will be obtained at each timepoint
Safety of GSK1940029 as assessed by dual lead telemetry
Time Frame: Pre-dose through 4h post-dose on Day 1 of Part 1 and Part 2
Continuous dual lead cardiac telemetry will be performed
Safety of GSK1940029 as assessed by hematology and chemistry parameters of clinical laboratory test
Time Frame: Screening, Days 1, 2 and FU (Days 6 to 8) of Part 1; Screening, Days 1, 4, 7, 14, and FU (Days 20 to 22) of Part 2
Safety of GSK1940029 as assessed by urinalysis parameters of clinical laboratory test
Time Frame: Screening, Days -1, 1, 2 and FU (Days 6 to 8) of Part 1; Screening, Days -1, 1, 2, 4, 7, 14, , and FU (Days 20 to 22) of Part 2
Safety of GSK1940029 as assessed by urine albumin:creatinine ratio (ACR)
Time Frame: Days -1, 1, 2 and FU (Days 6 to 8) of Part 1; Days -1, 1, 2, 4, 7, 14 and FU (Days 20 to 22) of Part 2
Safety of GSK1940029 as assessed by adverse events
Time Frame: Day -1 to FU (Days 6-8)of Part 1; Day -1 to FU (Day 20 - 22) of Part 2
Clinical monitoring/observation will be done for adverse events
Secondary Outcomes
- Plasma GSK1940029 pharmacokinetics (PK)(Part1: 1h, 2h, 4h, 6h, 8h, 12h, 16h, 22.5h, 24h and 36h post-dose. Part 2: 1h, 2h, 4h, 6h, 8h, 12h, 16h and 22.5h post-Day 1 dose; Pre-dose on Days 2, 12 and 13; and 1h, 2h, 4h, 6h, 8h, 12h, 16h, 22.5h and 22.5-24h post-Day 14 dose)
- Ocular tolerability of topical applications of GSK1940029(Screening, Days -1, 1, 2 and FU (Days 6 to 8) of Part 1; Screening, Days -1, 7, 14 and FU (Days 20 to 22) of Part 2)