Study to Evaluate the Safety, Tolerability and Pharmacokinetic of Single and 14 Day Repeat Topical Application of GSK1940029

NCT01938482 | Completed Phase 1

• 1 other identifier: 117226
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Acne Vulgaris

Keywords

SCD1; Topical Administration; Acne; Gel

Outcome Measures

Primary Outcomes (8)

• Safety of GSK1940029 as assessed by physical examination findings.

  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

  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

• Safety of GSK1940029 as assessed by vital signs

  Vital signs measurements will include systolic and diastolic blood pressure, heart rate and temperature

  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

• Safety of GSK1940029 as assessed by 12-lead electrocardiogram (ECG)

  Single 12-lead ECG will be obtained at each timepoint

  Screening, Day 1 and Day 2 of Part 1; Screening, Day 1, 2, 7, 12, 13 and 14 of Part 2

• Safety of GSK1940029 as assessed by dual lead telemetry

  Continuous dual lead cardiac telemetry will be performed

  Pre-dose through 4h post-dose on Day 1 of Part 1 and Part 2

• Safety of GSK1940029 as assessed by hematology and chemistry parameters of clinical laboratory test

  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

  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)

  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

  Clinical monitoring/observation will be done for adverse events

  Day -1 to FU (Days 6-8)of Part 1; Day -1 to FU (Day 20 - 22) of Part 2

Secondary Outcomes (2)

• 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

Study Arms (2)

Part 1

EXPERIMENTAL

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

Drug: 0.3% GSK1940029 gel; Drug: 1% GSK1940029 gel; Drug: 0.3%/1% vehicle gel only

Part 2

EXPERIMENTAL

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

Drug: 0.3% GSK1940029 gel; Drug: 1% GSK1940029 gel; Drug: 0.3%/1% vehicle gel only

Interventions

0.3% GSK1940029 gel DRUG

Will be supplied as gel for topical application

Part 1; Part 2

1% GSK1940029 gel DRUG

Will be supplied as gel for topical application

Part 1; Part 2

0.3%/1% vehicle gel only DRUG

Will be supplied as gel for topical application

Part 1; Part 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• History of severe, chronic asthma or significant allergies (including food, drug or cutaneous allergies). Subjects with the presence or a history of atopy (seasonal allergies, allergic rhinitis) or mild (limited) eczema will be allowed to participate in the study, although applications at sites with active eczema will not be allowed.
• Use of topical medications such as but not limited to retinoids, steroids, and transdermal hormone replacement therapies on or near the intended site of application within 8 weeks prior to dosing through treatment follow up. Use of other topical preparations such as those containing vitamins, supplements or herbal within 2 weeks prior to dosing through treatment follow up.
• Unable to refrain from the use of topical medications from the initial dose of study medication through follow-up.
• Foreseeable intensive ultraviolet (UV) exposure during the study (solar or artificial) as follows: subjects must not be exposed to direct sunlight for sun tanning or exposed to skin tanning devices (e.g. sunbed) for the duration of the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Adelaide, South Australia, 5000, Australia

Location

Related Links

• Results for study 117226 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Acne Vulgaris

Condition Hierarchy (Ancestors)

Acneiform Eruptions; Skin Diseases; Skin and Connective Tissue Diseases; Sebaceous Gland Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2013
• First Posted: September 10, 2013
• Study Start: October 31, 2013
• Primary Completion: February 17, 2015
• Study Completion: February 17, 2015
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

AU (1)