Phase 1, Randomized, Vehicle-Controlled, Double-Blind Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of Repeat Topical Application of BOS-356 in Subjects With Moderate to Severe Acne Vulgaris

This study is being conducted to characterize the safety and tolerability of BOS-356 in adult participants with moderate to severe acne vulgaris following 14 days or 28 days of repeated topical application

开始日期2019-11-04

申办/合作机构

Boston Pharmaceuticals, Inc.初创企业

NCT02742766 / Completed临床1期

A Phase I, Randomized, Placebo-Controlled, Double-Blind (Sponsor Unblind), Three Part Study to Evaluate the Safety, Tolerability, Preliminary PK and PD of Single and Repeat Oral Doses of GSK3008356 in Healthy Subjects and Obese Subjects

This study is a phase I, randomized, placebo-controlled, double-blind (sponsor unblind), three part study. The primary objective of the study is to characterize the safety, and tolerability of GSK3008356 single dose, 14 daily repeat doses in healthy subjects and 28 daily repeat doses in obese subjects. The study has three parts. Part 1, will be a single and multiple-dose, dose-rising study in healthy subjects. Part 2, will be a 14-day, repeat-dose, dose-rising study in healthy subjects, and part 3 will be a 28-day, repeat-dose study in obese subjects. For Parts 1 and 2, data from prior doses cohorts will be available prior to escalation decisions. Data from Parts 1 and 2 will be available prior to initiation of the three parallel cohorts in Part 3. A dose escalation meeting will be held to review these data and document the decision to proceed as planned or make any alterations in dosing, if indicated. Part 1, Part 2 and Part 3 study will have approximately 88, 24 and 30 subjects, respectively.

开始日期2016-03-14

申办/合作机构

GSK Plc

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100 项与 GSK-3008356 相关的临床结果

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100 项与 GSK-3008356 相关的转化医学

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100 项与 GSK-3008356 相关的专利（医药）

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项与 GSK-3008356 相关的文献（医药）

2019-11-01·Clinical Pharmacology in Drug Development

First‐in‐Human Pharmacokinetics and Safety Study of GSK3008356, a Selective DGAT1 Inhibitor, in Healthy Volunteers

Article

作者: Rieman, David ; Okour, Malek ; Zhu, Xinyi ; Brigandi, Richard A. ; Lickliter, Jason D. ; Gress, Angela

AbstractDiacylglycerol acyltransferase (DGAT) enzymes are involved in triglyceride (TG) biosynthesis. GSK3008356 is a potent and selective DGAT1 inhibitor that was administered orally in a 2‐part study as double‐blind, randomized, placebo‐controlled single doses (SDs) and repeat doses (RDs) in healthy subjects to investigate its pharmacokinetics, pharmacodynamics, and safety/tolerability. Gastrointestinal adverse events were considered drug related and increased with dose and when given as multiple doses. In the SD part (n = 80), GSK3008356 was dosed from 5 to 200 mg as single or multiple doses per day. In the RD part (n = 24), GSK3008356 was dosed twice daily at 1, 3, and 10 mg for 14 days. GSK3008356 was generally well tolerated in the SD and RD parts. With single doses, absorption was rapid (median tmax, 0.5–1.5 hours), whereas single‐day divided dosing resulted in higher tmax. Following 14‐day RD oral administration, GSK3008356 was also rapidly absorbed, with median tmax ranging from 0.5 to 0.75 hours on days 1 and 14. Estimated mean half‐life ranged from 1.5 to 4.6 hours with SDs and 1.3 to 2.1 hours with RDs. Exposure of GSK3008356 was largely dose proportional after RDs. At higher doses, there was a trend toward lower absolute postprandial TG level in some subjects.

2019-10-01·Fundamental & Clinical Pharmacology3区 · 医学

A population analysis of the DGAT1 inhibitor GSK3008356 and its effect on endogenous and meal‐induced triglyceride turnover in healthy subjects

3区 · 医学

Article

作者: Okour, Malek ; Brigandi, Richard A. ; Tenero, David

AbstractNon‐alcoholic steatohepatitis (NASH) is a liver disease in which fatty infiltration is accompanied by liver inflammation. GSK3008356 is under development as a selective inhibitor of diacylglycerol acyltransferase 1 (DGAT1), a key enzyme involved in the formation of triglyceride (TG). Decreased DGAT1 activity can reduce circulating TG and liver TG, and therefore could potentially prevent or treat NASH. The aim of the current study was to develop a population pharmacokinetic–pharmacodynamic (PKPD) model that characterizes the PK disposition of GSK3008356 and its relation to the changes in blood TG. Drug concentrations were measured in 104 healthy adults receiving various single (SD) and repeat doses (RD) in a first time in human (FiH) study. A 30% fat meal was given at hour 2 postdose, and blood postprandial TG concentrations were measured at various time points. The population PKPD model consists of several parts including a PK model, drug effect model, meal effect model, and a turnover model. The pharmacokinetic data were described using a 3‐compartment model. Drug effect was described by an inhibitory sigmoidal Emax model. Since TG levels change with the introduction of a meal, a bi‐exponential meal effect model was utilized. The total change in TG was fitted using a turnover model with drug and meal effects on the TG production rate. The current analysis presents a PKPD modeling strategy of time‐varying TG data coming from both endogenous and exogenous sources. In general, the presented model could be utilized in the model‐based drug development of drugs that influence TG levels in blood.

100 项与 GSK-3008356 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
寻常痤疮	临床1期	-	GSK Plc	-
中度至重度痤疮	临床前	加拿大	Boston Pharmaceuticals, Inc.初创企业	2019-11-04
中度至重度痤疮	临床前	美国	Boston Pharmaceuticals, Inc.初创企业	2019-11-04
肥胖	临床前	澳大利亚	GSK Plc	2016-03-14

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


Pubmed	N/A	-	-	GSK3008356	糧顧遞憲鑰鹽艱簾襯築(衊築廠壓廠網遞窪廠襯) = Gastrointestinal adverse events were considered drug related and increased with dose and when given as multiple doses 醖齋鏇鏇醖衊鏇築餘衊 (積壓鹹範襯製憲積窪夢 ) 更多	-	2019-11-01