Dataset from An Open Label, Randomised, Repeat Dose Study to Assess the Pharmacokinetic Performance of Five Ezogabine/Retigabine Modified Release (MR) Formulations at Steady State Compared to the Immediate Release (IR) Formulation.

This is an open-label, single centre, repeat dose, up- titration study in healthy male and female subjects to assess the pharmacokinetic (PK) performance of five prototypes of ezogabine modified release tablet formulations. The study will consist of a screening period, a treatment phase (consisting of a titration phase, bioavailability phase and food effect phase) and a post-treatment follow-up visit. The study duration from screening to follow up will be approximately 7 weeks. No study procedures will start before informed consent is obtained. Subjects will remain in the clinical unit for the duration of the treatment period (35 days). Subjects will receive repeat doses of ezogabine for up to 34 days starting at a dose of 100 mg IR TID (300mg TDD) with a standard meal (to be consumed 30 min prior to dosing) for Days 1-3, on days 4-6 subjects will receive 150mg IR TID (450mg TDD). On Day 7 through to the end of the study subjects will receive ezogabine (Mr or IR) at a dose of 600mgTDD. On Day 7 subjects will enter into a 6-way cross over period to investigate the 5 MR formulations being tested (each at 300mg BID) and the single IR formulation (at 200mg TID). Subjects will receive each formulaition for 4 days and blood samples for pharmacokinetic analysis will be collected up to 24 hours post dose on each 4th day (PK days). On Day 31 subjects will enter into a food effect phase to investigate the 5 MR formulations being tested (each at 600mg QD). Subjects in this period will have a PK day on Day 33 (following a standard breakfast), and on Day 34 (following a high fat breakfast) to investigate a food effect on the PK profile of ezogabine.

本研究为一项开放标签、单中心、重复给药剂量递增临床试验，旨在评估依佐加滨（ezogabine）五种缓释片制剂原型的药代动力学（pharmacokinetic, PK）表现，受试对象为健康男性及女性受试者。本研究流程包含筛选期、治疗期（含剂量递增阶段、生物利用度阶段与食物影响阶段）及治疗后随访访视。从筛选至随访的总研究周期约为7周。所有研究操作均需在获取受试者知情同意后方可启动。
治疗期间（共计35天）受试者需全程留驻临床研究单元。受试者将接受至多34天的依佐加滨重复给药：第1至3日给予100mg即时型（immediate release, IR）制剂，每日三次（总日剂量total daily dose, TDD 300mg），给药前30分钟进食标准餐；第4至6日给药剂量调整为150mg IR制剂，每日三次（TDD 450mg）。自第7日起至研究结束，受试者将接受总日剂量600mg的依佐加滨（缓释型modified release, MR或IR制剂）。
第7日起，受试者将进入6周期交叉试验阶段，以评价本次研究的5种MR制剂（均为300mg每日两次twice daily, BID）及1种IR对照制剂（200mg每日三次）。受试者将每种制剂连续给药4天，并于每给药周期的第4日（药代动力学采样日）采集给药后至多24小时的血样，用于药代动力学分析。
第31日，受试者进入食物影响试验阶段，评价本次研究的5种MR制剂（均为600mg每日一次once daily, QD）。该阶段受试者分别于第33日（标准早餐后）及第34日（高脂早餐后）接受药代动力学采样，以考察饮食对依佐加滨药代动力学特征的影响。