Document Detail


QT effect of semagacestat at therapeutic and supratherapeutic doses.
MedLine Citation:
PMID:  22456300     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Objective: This thorough QT/ QT interval corrected for heart rate (QTc) study was designed to assess the potential of semagacestat, a functional gamma-secretase inhibitor, to delay cardiac repolarization. Methods: In this Phase I, single-dose, randomized, 4-period crossover study, semagacestat was compared with placebo in 54 healthy male and female subjects between the ages of 19 and 63 years, inclusive. Each study period included single oral-dose administrations of semagacestat 140 mg, semagacestat 280 mg, moxifloxacin 400 mg, or placebo. Study subjects and the investigator were blinded to the identity of semagacestat and placebo; however, moxifloxacin was administered as open-label. Moxifloxacin was compared with placebo for assay sensitivity analysis. Pharmacokinetic parameters were also assessed. Results: For each QTc, the upper bound of the 2-sided 90% confidence interval (CI) for the least squares mean difference between semagacestat (at both the 140- and 280-mg dose levels) and placebo was < 10 msec at all time points, and thus, within the limits set for clinical relevance in regulatory guidelines. Conclusions: The results of this study indicate that single doses of 140 and 280 mg semagacestat did not prolong QTc to a clinically significant degree.
Authors:
Wei Zhang; Mosun Ayan-Oshodi; Brian A Willis; William Annes; Stephen D Hall; Joseph Chiesa; Mary Seger
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of clinical pharmacology and therapeutics     Volume:  50     ISSN:  0946-1965     ISO Abbreviation:  Int J Clin Pharmacol Ther     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423309     Medline TA:  Int J Clin Pharmacol Ther     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  290-9     Citation Subset:  IM    
Affiliation:
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA, and Covance Clinical Research Unit Ltd, Springfield House, Leeds, UK.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Cost comparison of outpatient treatment with granulocyte colony-stimulating factors (G-CSF) in Germa...
Next Document:  Myoclonus precipitated by oral suspension of oxcarbazepine in idiopathic generalized epilepsy.