A Phase I, Open-Label, Single-Dose, Multi-Part Study to Assess the Pharmacokinetics of Gepotidacin (GSK2140944) in Male and Female Adult Subjects With Varying Degrees of Renal Impairment and in Matched Control Subjects With Normal Renal Function

This study will be conducted to determine if altered renal function affects the plasma pharmacokinetics of gepotidacin, which will inform if dosing recommendations based upon renal impairment are required. The objective of this study is to compare the pharmacokinetics of gepotidacin administered as a 750 milligram (mg) intravenous (IV) dose in normal healthy subjects compared with subjects with mild, moderate, and severe renal impairment, and with subjects with end stage renal disease (ESRD). This is a Phase I, nonrandomized, open-label, parallel-group, multi-center, multi-part study. In Part 1, up to 16 subjects with normal renal function will be matched to approximately 8 subjects with moderate renal impairment, and approximately 8 subjects with severe renal impairment and/or subjects with ESRD not on hemodialysis for a total of approximately 32 subjects. In Part 2 (optional), approximately 4 to 8 subjects with normal renal function (if enrolled), approximately 4 to 8 subjects with mild renal impairment, and approximately 4 to 8 subjects with ESRD on hemodialysis will be enrolled for a total of approximately 12 to 24 subjects. The duration from Screening to the Follow-up Visit will be approximately 44 days for Part 1 and approximately 50 days for Part 2.

本研究旨在明确肾功能异常是否会影响吉特达星（gepotidacin）的血浆药代动力学，为是否需要针对肾功能不全人群调整给药方案提供依据。本研究的核心目标为对比单次给予750毫克（mg）静脉注射（intravenous, IV）剂量的吉特达星后，肾功能正常受试者、轻度、中度及重度肾功能不全受试者，以及终末期肾病（end stage renal disease, ESRD）受试者体内的药代动力学差异。本研究为I期非随机开放标签平行组多中心多分部临床试验。其中第1部分将至多纳入16名肾功能正常受试者，并与约8名中度肾功能不全受试者、约8名重度肾功能不全受试者以及未接受血液透析的终末期肾病受试者进行匹配分组，总受试者规模约为32例。第2部分为可选分部，将纳入约4~8名肾功能正常受试者（若完成入组）、约4~8名轻度肾功能不全受试者，以及约4~8名接受血液透析的终末期肾病受试者，总受试者人数约为12~24例。第1部分受试者从筛选至随访访视的总时长约为44天，第2部分则约为50天。