A Single-centre, Masked, Placebo-controlled Four Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of the CC-chemokine Receptor 3 (CCR3) Antagonist, GW824575, Coadministered With or Without Food in Healthy Male Subjects

This study is the first administration of GW824575 in humans. This will be a single centre, masked, placebo-controlled study, to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GW824575, given as single and repeated oral doses to healthy male subjects. The study will be comprised of 4 parts and enroll approximately 40 subjects: Part A will consist of two cohorts of 8 healthy male subjects to assess the safety, tolerability, PK, and PD of ascending single oral doses of GW824575. All available safety, tolerability, and PK data will be monitored prior to each dose escalation. In order to support the possible indication for age-related macular degeneration (AMD), Part B will be one cohort of 12 subjects to examine the safety, tolerability, PK, and PD of a repeated dose of GW824575 over 21 days in healthy male subjects who are greater than or equal to 50 years of age. The total daily dose in this cohort will not exceed the maximum tolerated dose (MTD) from Parts A and D. Subjects in this cohort will undergo ophthalmology assessments before receiving investigational product and after Day 7 of the 21-day in-patient treatment, after steady state has been reached. As part of protocol amendment 2, Part C (Cohort 4) is removed from the protocol. Part D, added under protocol amendment 2, will consist of one cohort of 12 healthy male subjects to assess safety, tolerability, PK, and PD of ascending single doses of GW824575 as well as the effect of food on the PK of GW824575.

本研究为GW824575首次人体临床试验。本试验为单中心、设盲、安慰剂对照研究，旨在探究单次及多次口服给药的GW824575在健康男性受试者中的安全性、耐受性、药代动力学（Pharmacokinetics, PK）与药效动力学（Pharmacodynamics, PD）。试验共分为4个部分，计划招募约40名受试者：A部分将设置2个队列，每队列纳入8名健康男性受试者，用于评估递增剂量单次口服GW824575的安全性、耐受性、PK及PD。每次剂量爬坡前，均需对已获取的全部安全性、耐受性及PK数据进行监查。为支持年龄相关性黄斑变性（Age-Related Macular Degeneration, AMD）的潜在适应症开发，B部分将设置1个队列，纳入12名年龄≥50岁的健康男性受试者，评估21天重复给药GW824575的安全性、耐受性、PK及PD。该队列的每日总剂量不得超过A部分与D部分中确定的最大耐受剂量（Maximum Tolerated Dose, MTD）。本队列受试者将在接受试验药物前，以及达到血药浓度稳态后的21天住院治疗第7天后，接受眼科评估。根据方案修正案2，原C部分（队列4）已从试验方案中移除。依据方案修正案2新增的D部分，将设置1个队列，纳入12名健康男性受试者，用于评估递增剂量单次口服GW824575的安全性、耐受性、PK及PD，同时探究食物对GW824575 PK的影响。