Dataset from A Single-centre, Double-blind (Sponsor Open), Placebo Controlled Two Part Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of GSK2292767 as a Dry Powder in Healthy Participants Who Smoke Cigarettes

This study is the first administration of GSK2292767 to humans. The study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and repeat inhaled doses of GSK2292767 in healthy smokers. This study is intended to provide sufficient confidence in the safety of the molecule and preliminary information on target engagement to allow progression to further repeat dose and proof of mechanism studies. This is a two part, single site, randomized, double-blind (sponsor open), placebo controlled study. Part A will consist of two 3-period interlocking cohorts to evaluate the safety, tolerability and pharmacokinetics of ascending single doses of GSK2292767 administered as a dry powder inhalation. Part B is planned to follow Part A and progression will be based on an acceptable safety, tolerability and pharmacokinetic profiles. Subjects will receive repeat doses of GSK2292767 once daily for 14 days during Part B.

本研究为GSK2292767首次应用于人体的临床试验。本研究将评估健康吸烟者单次及多次吸入给药时，GSK2292767的安全性、耐受性、药代动力学（pharmacokinetics, PK）与药效动力学（pharmacodynamics, PD）。本研究旨在为该化合物的安全性提供充分依据，并获取靶点结合的初步信息，以支持后续开展多次给药及机制验证研究。本研究为分两阶段的单中心、随机、双盲（申办方开放）、安慰剂对照临床试验。A阶段将设置两个3周期交错队列，以评估以干粉吸入方式给予递增单次剂量的GSK2292767的安全性、耐受性及药代动力学。B阶段计划紧随A阶段开展，其启动将基于合格的安全性、耐受性及药代动力学特征。B阶段期间，受试者将每日一次接受GSK2292767多次给药，持续14天。