In binding is estimated to be 69 on the basis of in vitro study results (data not shown). GSK1322322 shows no crossresistance with agents in existing use and is fully active against pathogens resistant to various classes of existing antibiotics, such as betalactams, macrolides, and quinolones (9). GSK1322322 is active against communityacquired skin and respiratory tract pathogens, like MRSA, multidrugresistant S. pneumoniae, and atypical pathogens (5, 9, ten). GSK1322322 exhibits a potent subMIC effect for many strains of S. aureus, inhibiting development in vitro for six to 8 h at concentrations effectively under the MIC (11, 12). The potent in vivo activity of GSK1322322 against rodent respiratory tract infection and skin and soft tissue infection models has been demonstrated (five, 9). The favorable MIC and animal information coupled together with the security profile ofTGSK1322322 observed to date support further clinical development of GSK1322322 in target patient populations. In this 2part, phase I study, GSK1322322 was 1st administered in humans to evaluate its security, tolerability, and singledose pharmacokinetics (PK) with dose escalation from one hundred to 1,500 mg in healthful volunteers (10). The safety, tolerability, and PK of larger doses (two,000 to 4,000 mg) have been also assessed. Also, simply because GSK1322322 has pHdependent solubility, the effect of a highfat meal around the PK of GSK1322322 was evaluated.Components AND METHODSStudy design and population. This was a randomized, doubleblind, placebocontrolled, singledose, sequentialcohort, dose escalation trial of healthy volunteers (study identifier PDF111341). Adults aged 18 to 65 years who had been in commonly great health with no clinically relevant abnormalities as determined by healthcare history, physical examination, laboratory tests, and cardiac monitoring were eligible for the trial. Volunteers had a physique mass index of 18 to 30 kg/m2, inclusive. Volunteers were excluded from the study if they met among the following criteria: a constructive prestudy drug/alcohol screen; optimistic hepatitis B virus surface antigen or hepatitis C virus antibody outcome inside 3 months of screening; good test for HIV antibody; use of any investigational drug within 30 days, five halflives, or twice the duration of the biological effect with the investigational drug (whichever is longer) before the day of dosing; or exposure toReceived 29 August 2012 Returned for modification 1 October 2012 Accepted eight December 2012 Published ahead of print 12 February 2013 Address correspondence to Odin J.5-Ethynyluridine uses Naderer, odin.1212934-10-5 site j.PMID:33638709 [email protected]. Copyright 2013, American Society for Microbiology. All Rights Reserved. doi:10.1128/AAC.01779May 2013 Volume 57 NumberAntimicrobial Agents and Chemotherapyp. 2005aac.asm.orgNaderer et al.4 new chemical entities inside 12 months before the day of dosing. All volunteers provided written informed consent. The study was authorized by an institutional critique board and was conducted in accordance with great clinical practices. All round, 9 cohorts had been planned for this 2part study. Element A was planned with 6 cohorts: 5 cohorts to study the singledose safety, tolerability, and PK with dose escalation from 100 to 1,500 mg (i.e., cohorts A to E) under fasting conditions and 1 cohort (i.e., cohort G) to assess the impact of a highfat meal on PK parameters using the chosen 800mg GSK1322322 dose (depending on safety and tolerability at earlier doses and consideration from the expected increase in GSK1322322 exposures). The study was design and style.
