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Thorough QTc Study of a Single Supratherapeutic Dose of Relebactam in Healthy Participants
Author(s) -
Boundy Keith,
Liu Yang,
Bhagunde Pratik,
O'Reilly Terry E.,
ColonGonzalez Francheska,
Friedman Evan J.,
Lala Mallika,
Rhee Elizabeth G.,
Rizk Matthew L.
Publication year - 2020
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.786
Subject(s) - medicine , moxifloxacin , qt interval , placebo , confidence interval , crossover study , population , assay sensitivity , anesthesia , cardiology , pharmacology , antibiotics , alternative medicine , environmental health , pathology , microbiology and biotechnology , biology
The effects of supratherapeutic doses of intravenous (IV) relebactam on duration of ventricular depolarization and subsequent repolarization were assessed in a thorough QT/corrected QT study. This was a single‐dose, double‐blind (relebactam only), randomized, placebo‐ and positive‐controlled, 3‐period, balanced crossover study in healthy participants. Participants received in randomized order, and separated by a washout (≥4 days), a single dose of IV relebactam 1150 mg, oral moxifloxacin 400 mg (open‐label positive control), and IV placebo. Least squares mean and 2‐sided 90% confidence interval for change from baseline in population‐derived corrected QT intervals for relebactam, moxifloxacin, and placebo were estimated for 24 hours. The upper limit of the 90% confidence interval of all least squares mean population‐derived corrected QT treatment differences from placebo was not >10 milliseconds at any time point for 24 hours. Corrected QT assay sensitivity was confirmed with moxifloxacin treatment. Analysis of electrocardiogram parameters resulted in no additional cardiac safety concerns. Overall, a supratherapeutic dose of relebactam yielded no cardiac safety events; the 1150‐mg supratherapeutic dose (4.6‐fold above the 250‐mg therapeutic dose) was not associated with QT prolongation or other abnormal cardiodynamic parameters. This study lends additional support to relebactam's use as a β‐lactamase inhibitor in antimicrobial therapy.