PMID- 25845864
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20220321
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 59
IP  - 6
DP  - 2015
TI  - A thorough QT study to evaluate the effects of therapeutic and supratherapeutic 
      doses of delafloxacin on cardiac repolarization.
PG  - 3469-73
LID - 10.1128/AAC.04813-14 [doi]
AB  - A randomized, double-blind, placebo-controlled, 4-period crossover study was 
      conducted in 52 healthy adults to assess the effect of delafloxacin on the 
      corrected QT (QTc) interval. The QT interval, corrected for heart rate using 
      Fridericia's formula (QTcF), was determined predose and at 0.5, 1, 1.25, 1.5, 
      1.75, 2, 2.5, 3, 4, 5, 6, 12, 18, and 24 h after dosing with delafloxacin at 300 
      mg intravenously (i.v.; therapeutic), delafloxacin at 900 mg i.v. 
      (supratherapeutic), moxifloxacin at 400 mg orally (p.o.; positive control), and 
      placebo. The pharmacokinetic profile of delafloxacin was also evaluated. At each 
      time point after delafloxacin administration, the upper limit of the 90% 
      confidence interval (CI) for the placebo-corrected change from the predose 
      baseline in QTcF (DeltaDeltaQTcF) was less than 10 ms (maximum, 3.9 ms at 18 h after 
      dosing), indicating an absence of a clinically meaningful increase in the QTc 
      interval. The lower limit of the 90% CI of DeltaDeltaQTcF for moxifloxacin versus placebo 
      was longer than 5 ms at all 5 time points selected for assay sensitivity 
      analysis, demonstrating that the study was adequately sensitive to assess QTc 
      prolongation. There was no positive relationship between delafloxacin plasma 
      concentrations and DeltaDeltaQTcF. Treatment-emergent adverse events (AEs) were more 
      frequent among subjects receiving a single supratherapeutic dose of 900 mg 
      delafloxacin. There were no deaths, serious AEs, or AEs leading to study 
      discontinuation and no clinically meaningful abnormalities in laboratory values 
      or vital signs observed at any time point after any dose of the study drug.
CI  - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved.
FAU - Litwin, Jeffrey S
AU  - Litwin JS
AD  - ERT, Philadelphia, Pennsylvania, USA JLitwin@ert.com.
FAU - Benedict, Michael S
AU  - Benedict MS
AD  - PPD Inc., Austin, Texas, USA.
FAU - Thorn, Michael D
AU  - Thorn MD
AD  - Statistical Resources, Chapel Hill, North Carolina, USA.
FAU - Lawrence, Laura E
AU  - Lawrence LE
AD  - Melinta Therapeutics, New Haven, Connecticut, USA.
FAU - Cammarata, Sue K
AU  - Cammarata SK
AD  - Melinta Therapeutics, New Haven, Connecticut, USA.
FAU - Sun, Eugene
AU  - Sun E
AD  - Melinta Therapeutics, New Haven, Connecticut, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150406
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Fluoroquinolones)
RN  - 6315412YVF (delafloxacin)
RN  - U188XYD42P (Moxifloxacin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anti-Bacterial Agents/*pharmacokinetics/*pharmacology
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Electrocardiography
MH  - Female
MH  - Fluoroquinolones/*pharmacokinetics/*pharmacology
MH  - Healthy Volunteers
MH  - Heart/*drug effects
MH  - Humans
MH  - Male
MH  - Moxifloxacin
MH  - Young Adult
PMC - PMC4432193
EDAT- 2015/04/08 06:00
MHDA- 2016/02/18 06:00
PMCR- 2015/05/14
CRDT- 2015/04/08 06:00
PHST- 2014/11/14 00:00 [received]
PHST- 2015/03/22 00:00 [accepted]
PHST- 2015/04/08 06:00 [entrez]
PHST- 2015/04/08 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
PHST- 2015/05/14 00:00 [pmc-release]
AID - AAC.04813-14 [pii]
AID - 04813-14 [pii]
AID - 10.1128/AAC.04813-14 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2015;59(6):3469-73. doi: 10.1128/AAC.04813-14. Epub 
      2015 Apr 6.