• Clin Pharmacol Drug Dev · Sep 2018

    Randomized Controlled Trial

    Evaluation of Eluxadoline Effect on Cardiac Repolarization.

    • Laura Bonifacio, Thomas L Hunt, Gail McIntyre, Leonard S Dove, and Paul S Covington.
    • Lodestar Pharma Consulting, LLC, Durham, NC, USA.
    • Clin Pharmacol Drug Dev. 2018 Sep 1; 7 (7): 727-736.

    AbstractThis study evaluated the effects of eluxadoline, a mixed μ-opioid receptor (OR) and κ-OR agonist and δ-OR antagonist, on cardiac repolarization. This evaluator-blinded, placebo- and positive-controlled, 4-period crossover study randomized healthy men and women to single oral doses of eluxadoline (therapeutic dose 100 mg or supratherapeutic dose 1000 mg), moxifloxacin 400 mg, or placebo. QT data were corrected using individual custom correction (QTcI). The primary endpoint was the change from baseline in QTcI intervals (ΔQTcI) between eluxadoline and placebo (ΔΔQTcI). An upper bound of the 95% confidence interval around ΔΔQTcI of 10 milliseconds was considered clinically significant. Concentration-QTc data were analyzed using a repeated-measures, mixed-effects linear model. Sixty-four volunteers were treated, and 58 completed the study. Assay sensitivity was demonstrated with moxifloxacin (noted by ΔΔQTcI of 11.94 milliseconds). The maximum ΔΔQTcI for eluxadoline 1000 mg was 4.10 milliseconds 1 hour postdose (1-sided 95% upper confidence bound, 5.81 milliseconds), and for eluxadoline 100 mg was 1.20 milliseconds at 0.5 hours postdose (1-sided 95% upper confidence bound, 2.91 milliseconds). Primary ΔΔQTcI results were confirmed using Fridericia's formula for QTc. Categorical, morphological, and concentration-QTc analyses were consistent with the primary and secondary findings. There were no significant gender effects on ΔΔQTcI values. The most common adverse events were contact dermatitis and nausea (12.5% each) and dizziness (10.9%); adverse events were more frequent in the eluxadoline 1000 mg group. In conclusion, eluxadoline, at therapeutic or supratherapeutic doses, did not significantly prolong QT intervals, and was safe and generally well tolerated in this study population.© 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…