A Study to Evaluate Pharmacokinetic (PK), Safety and Tolerability of GSK2894512 in Healthy Adult Subjects

NCT03201978 | Withdrawn Phase 1

• 1 other identifier: 207539
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

GSK2894512 (trans-isomer) is a fully synthetic, non-steroidal anti-inflammatory agent. This study is being conducted to evaluate the PK, safety and tolerability of GSK2894512 cream, 1 percent administered topically to healthy adult subjects. PK parameters obtained in this study will be used to support the design of future maximum use PK (MUPK) studies in subjects with atopic dermatitis (AD) and plaque psoriasis or psoriasis (PSO). This is a phase 1, randomized, double-blind, vehicle-controlled, 3-period, sequential, inpatient study consists of a Screening visit, 3 treatment periods and a follow-up visit. GSK2894512 cream, 1 percent (or matching vehicle) will be administered sequentially in the treatment periods. Period 1 will include once daily repeated topical applications on approximately 5000 centimeter (cm) \^2 intact non-occluded skin area for 21 days. Period 2 will include once daily repeated topical applications on approximately 5000 cm\^2 intact occluded skin area for 21 days. Period 3 will include a single topical application on up to 400 cm\^2 gently taped-stripped skin area. Each treatment regimen will be followed by washout period for approximately 21 days, except for Treatment Period 3. Approximately 26 healthy adult subjects will be enrolled in to the study. Total duration of participation in this study will be approximately 18 weeks.

Conditions

Psoriasis

Keywords

Healthy adults; GSK2894512; Topical; Psoriasis; Pharmacokinetics

Outcome Measures

Primary Outcomes (8)

• Plasma concentrations of GSK2894512 (trans-isomer)

  Blood samples will be collected at the indicated time points to evaluate plasma concentration of GSK2894512 (trans-isomer).

  Days 1, 7, 14, 21: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16 hours; Days 2, 3, 8, 9, 15, 16, 22, 23: Pre-dose, in Period-1 and 2. Period-3: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 48 hours

• Area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUC [0-tau]) of GSK2894512

  Blood sample will be collected at the indicated time points to evaluate PK profile of GSK2894512.

  Days 1, 7, 14, 21: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16 hours; Days 2, 3, 8, 9, 15, 16, 22, 23: Pre-dose, in Period-1 and 2. Period-3: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 48 hours

• Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC [0-t) of GSK2894512

  Blood sample will be collected at the indicated time points to evaluate PK profile of GSK2894512.

  Days 1, 7, 14, 21: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16 hours; Days 2, 3, 8, 9, 15, 16, 22, 23: Pre-dose, in Period-1 and 2. Period-3: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 48 hours

• Maximum observed serum concentration (Cmax) of GSK2894512

  Blood sample will be collected at the indicated time points to evaluate PK profile of GSK2894512.

  Days 1, 7, 14, 21: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16 hours; Days 2, 3, 8, 9, 15, 16, 22, 23: Pre-dose, in Period-1 and 2. Period-3: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 48 hours

• Time of maximum concentration observed (tmax) of GSK2894512

  Blood sample will be collected at the indicated time points to evaluate PK profile of GSK2894512.

  Days 1, 7, 14, 21: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16 hours; Days 2, 3, 8, 9, 15, 16, 22, 23: Pre-dose, in Period-1 and 2. Period-3: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 48 hours

• Apparent terminal phase half life (t1/2) of GSK2894512

  Blood sample will be collected at the indicated time points to evaluate PK profile of GSK2894512.

  Days 1, 7, 14, 21: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16 hours; Days 2, 3, 8, 9, 15, 16, 22, 23: Pre-dose, in Period-1 and 2. Period-3: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 48 hours

• Trough concentration at the end of the dosing interval (Ctau) of GSK2894512

  Blood sample will be collected at the indicated time points to evaluate PK profile of GSK2894512.

  Days 1, 7, 14, 21: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16 hours; Days 2, 3, 8, 9, 15, 16, 22, 23: Pre-dose, in Period-1 and 2. Period-3: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 48 hours

• Accumulation ratio (Ro) of GSK2894512

  Blood sample will be collected at the indicated time points to evaluate PK profile of GSK2894512.

  Days 1, 7, 14, 21: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16 hours; Days 2, 3, 8, 9, 15, 16, 22, 23: Pre-dose, in Period-1 and 2. Period-3: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 48 hours

Secondary Outcomes (7)

• Number of subjects with any adverse events (AEs) and serious AEs (SAEs)

  Up to 14 weeks

• Number of subjects with abnormal vital sign findings

  Up to 13 weeks

• Number of subjects with abnormal electrocardiogram (ECG) findings

  Up to 13 weeks

• Number of subjects with abnormal findings in digital holter monitoring

  Up to 13 weeks

• Number of subjects with abnormal findings in physical examination

  Up to 13 weeks

Study Arms (2)

GSK2894512 cream group

EXPERIMENTAL

Subjects will receive once daily topical repeated application on approximately 5000 cm\^2 intact non-occluded skin for 21 days in period 1 followed by once daily on 5000 cm\^2 intact occluded skin for 21 days in period 2 (after approximately 21 days of washout period), followed by a single topical application on up to 400 cm\^2 gently tape stripped skin area in period 3.

Drug: GSK2894512 1% CREAM

Vehicle cream group

PLACEBO COMPARATOR

Subjects will receive once daily topical repeated application on approximately 5000 cm\^2 intact non-occluded skin for 21 days in period 1 followed by once daily on 5000 cm\^2 intact occluded skin for 21 days in period 2 (after approximately 21 days of washout period), followed by a single topical application on up to 400 cm\^2 gently tape stripped skin area in period 3.

Drug: GSK2894512 MATCHING VEHICLE CREAM

Interventions

GSK2894512 1% CREAM DRUG

It will be prepared as close as possible to the time of administration to avoid a prolonged exposure to light. Each single cream application will be made by weight, dispensed on hand (fingertips) covered with clean disposable glove and evenly spread using fingertips.

GSK2894512 cream group

GSK2894512 MATCHING VEHICLE CREAM DRUG

It will be prepared as close as possible to the time of administration to avoid a prolonged exposure to light. Each single cream application will be made by weight, dispensed on hand (fingertips) covered with clean disposable glove and evenly spread using fingertips.

Vehicle cream group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• A history of ongoing serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, may interfere with the subject's completion of the study.
• A history or presence of skin disorders (e.g., irritant contact dermatitis); history or presence of hypertrophic scarring tissue or keloid formation in scars or needle puncture sites; a tattoo, body piercing or branding located on the study medication application site; excessive body hair that in the Investigator's opinion, may interfere with the areas designated for study medication application.
• Presence or history of AD or PSO.
• Presence of erosions, lacerations, abrasions, dermatitis or any other lesion on the lower legs that could increase absorption of GSK2894512.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Subject has a history of hyperhidrosis.
• Subject had a major surgery within 8 weeks prior to Baseline (Day -1) or has a major surgery planned during the study.
• Known hypersensitivity to GSK2894512 or excipients of the study treatments, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation.
• Abnormal aspartate aminotransferase (AST), alanine aminotransferase (ALT) or bilirubin values at screening
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV) antibody test results at screening.
• Presence of out-of-range cardiac interval (PR \<110 millisecond (msec), PR \>220 msec, QRS \<60msec, QRS \>119msec and QTcF \> 450msec) on the screening ECG (average of the triplicate ECG) or other clinically significant ECG abnormalities.
• Any history of latent or active tuberculosis (TB) and/or prophylaxis for tuberculosis according to the TB Medical History screening questionnaire.
• Subjects who took an investigational product (in another clinical trial) in the previous 30 days before day 1 of this study.
• Use of any medicated topical product on the same areas as study medication applications within 2 weeks prior to admission to clinical research center (CRC) on Day -1 and throughout each inpatient treatment period.
• Use of any topical products (apart from medicated topical products), except soap and gentle cleansers (example, moisturizers), on the same areas as study medication applications within 2 days prior to admission to CRC on Day -1 and throughout each inpatient treatment period.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• iCardiac Technologies, Inc.: collaborator
• Innovaderm Research Inc.: collaborator
• PPD Development, LP: collaborator
• Algorithme: collaborator

MeSH Terms

Conditions

Psoriasis

Interventions

tapinarof

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2017
• First Posted: June 28, 2017
• Study Start: December 14, 2017
• Primary Completion: May 15, 2018
• Study Completion: May 15, 2018
• Last Updated: November 29, 2017

Record last verified: 2017-11