PMID- 23617452
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20211021
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 12
DP  - 2013 Apr 24
TI  - The sodium glucose cotransporter 2 inhibitor empagliflozin does not prolong QT 
      interval in a thorough QT (TQT) study.
PG  - 70
LID - 10.1186/1475-2840-12-70 [doi]
AB  - BACKGROUND: Empagliflozin is a potent, selective sodium glucose cotransporter 2 
      (SGLT2) inhibitor in development as an oral antidiabetic treatment. This QT 
      interval study assessed potential effects of empagliflozin on ventricular 
      repolarisation and other electrocardiogram (ECG) parameters. METHODS: A 
      randomised, placebo-controlled, single-dose, double-blind, five-period crossover 
      study incorporating a novel double-placebo period design to reduce sample size, 
      while maintaining full statistical power. TREATMENTS: single empagliflozin doses 
      of 25 mg (therapeutic) and 200 mg (supratherapeutic), matching placebo and 
      open-label moxifloxacin 400 mg (positive control). Triplicate 12-lead ECGs of 10 
      second duration were recorded at baseline and during the first 24 hours after 
      dosing. The primary endpoint was mean change from baseline (MCfB) in the 
      population heart rate-corrected QT interval (QTcN) between 1-4 hours after 
      dosing. RESULTS: Thirty volunteers (16 male, 14 female, mean [range] age: 34.5 
      [18-52] years) were randomised. The placebo-corrected MCfB in QTcN 1-4 hours 
      after dosing was 0.6 (90% CI: -0.7, 1.9) ms and -0.2 (-1.4, 0.9) ms for 
      empagliflozin 25 mg and 200 mg, respectively, below the ICH E14 defined threshold 
      of regulatory concern 10 ms. Assay sensitivity was confirmed by a 
      placebo-corrected MCfB in QTcN 2-4 hours post-dose of 12.4 (10.7, 14.1) ms with 
      moxifloxacin 400 mg. Empagliflozin tolerability was good for all volunteers; 
      23.3% experienced adverse events (AEs) with empagliflozin and 27.6% with placebo. 
      The most frequent AE was nasopharyngitis. CONCLUSIONS/INTERPRETATION: Single 
      doses of empagliflozin 25 mg and 200 mg were not associated with QTcN 
      prolongation and were well tolerated in healthy volunteers. TRIAL REGISTRATION: 
      ClinicalTrials.gov: NCT01195675.
FAU - Ring, Arne
AU  - Ring A
FAU - Brand, Tobias
AU  - Brand T
FAU - Macha, Sreeraj
AU  - Macha S
FAU - Breithaupt-Groegler, Kerstin
AU  - Breithaupt-Groegler K
FAU - Simons, Gudrun
AU  - Simons G
FAU - Walter, Beate
AU  - Walter B
FAU - Woerle, Hans J
AU  - Woerle HJ
FAU - Broedl, Uli C
AU  - Broedl UC
LA  - eng
SI  - ClinicalTrials.gov/NCT01195675
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130424
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Fluoroquinolones)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (SLC5A2 protein, human)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - HDC1R2M35U (empagliflozin)
RN  - U188XYD42P (Moxifloxacin)
SB  - IM
MH  - Action Potentials
MH  - Adolescent
MH  - Adult
MH  - Benzhydryl Compounds/*adverse effects/pharmacokinetics
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Electrocardiography
MH  - Female
MH  - Fluoroquinolones/adverse effects
MH  - Germany
MH  - Glucosides/*adverse effects/pharmacokinetics
MH  - Heart Conduction System/*drug effects/physiopathology
MH  - Heart Rate/*drug effects
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects/pharmacokinetics
MH  - Long QT Syndrome/*chemically induced/diagnosis/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Moxifloxacin
MH  - Risk Assessment
MH  - Risk Factors
MH  - Sodium-Glucose Transporter 2/metabolism
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Time Factors
MH  - Young Adult
PMC - PMC3648489
EDAT- 2013/04/27 06:00
MHDA- 2015/03/31 06:00
PMCR- 2013/04/24
CRDT- 2013/04/27 06:00
PHST- 2012/12/19 00:00 [received]
PHST- 2013/04/02 00:00 [accepted]
PHST- 2013/04/27 06:00 [entrez]
PHST- 2013/04/27 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2013/04/24 00:00 [pmc-release]
AID - 1475-2840-12-70 [pii]
AID - 10.1186/1475-2840-12-70 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2013 Apr 24;12:70. doi: 10.1186/1475-2840-12-70.