scholarly journals Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone

2018 ◽  
Vol 12 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Jay W. Mason ◽  
Rakesh Chugh ◽  
Anasuya Patel ◽  
Ranjeet Gutte ◽  
Ashima Bhatia
Keyword(s):  
Supratherapeutic Dose

A Single Supratherapeutic Dose of Vorinostat Does Not Prolong the QTc Interval in Patients with Advanced Cancer

2009 ◽  
Vol 15 (22) ◽  
pp. 7077-7084 ◽  
Author(s):  
Pamela N. Munster ◽  
Eric H. Rubin ◽  
Simon Van Belle ◽  
Evan Friedman ◽  
Jaclyn K. Patterson ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Qtc Interval ◽  
Supratherapeutic Dose

scholarly journals Supratherapeutic dose evaluation and effect of lesinurad on cardiac repolarization: a thorough QT/QTc study

2016 ◽  
Vol Volume 10 ◽  
pp. 3509-3517 ◽  
Author(s):  
Zancong Shen ◽  
Michael Gillen ◽  
Kathy Tieu ◽  
Mai Nguyen ◽  
Erin Harmon ◽  
...  
Keyword(s):  
Cardiac Repolarization ◽  
Dose Evaluation ◽  
Supratherapeutic Dose

scholarly journals No Effect of a Single Supratherapeutic Dose of Lersivirine, a Next-Generation Nonnucleoside Reverse Transcriptase Inhibitor, on Corrected QT Interval in Healthy Subjects

2012 ◽  
Vol 56 (5) ◽  
pp. 2408-2413 ◽  
Author(s):  
Manoli Vourvahis ◽  
Rong Wang ◽  
Marie-Noella Ndongo ◽  
Melissa O'Gorman ◽  
Margaret Tawadrous
Keyword(s):  
Upper Bound ◽  
Healthy Subjects ◽  
Vital Signs ◽  
Transcriptase Inhibitor ◽  
Qtc Interval ◽  
Adult Males ◽  
Supratherapeutic Dose ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Clinically Significant ◽  
Mean Differences

ABSTRACTThe objective of this study was to investigate the effect of a supratherapeutic dose of lersivirine (LRV) on corrected QT (QTc) interval using Fridericia's equation (QTcF) in healthy subjects. In this randomized, single-dose, placebo- and active-controlled 3-way crossover study, healthy adult males (n= 48) were randomized to receive LRV (2,400 mg), moxifloxacin (400 mg), or placebo for each treatment period. Triplicate 12-lead electrocardiogram measurements were performed, PK samples were collected, and vital signs were measured. Adverse event monitoring and safety laboratory testing were performed. All subjects were white (mean age, 39 years; body mass index [BMI], 25.6 kg/m2) and completed the study. Following LRV administration, the upper bound of the 90% confidence interval (CI) for time-matched adjusted mean differences to placebo QTcF at each time point postdose was below the regulatory threshold of 10 ms, satisfying the criteria for a negative thorough QT/QTc study. The highest upper bound of QTcF 90% CI occurred at 6 h for LRV (3.32 ms; 90% CI, 1.47 to 5.17 ms). The study was deemed adequately sensitive as the lower bound of the 90% CI for the adjusted mean QTcF differences between moxifloxacin and placebo at the moxifloxacin historicalTmaxof 3 h was >5 ms (15.29 ms; 90% CI, 13.44 to 17.14 ms). There was no statistically significant relationship between LRV exposure and placebo-adjusted change from baseline QTcF or clinically significant changes in QRS complex, pulse rate (PR) interval, heart rate, or blood pressure. LRV (2,400 mg) did not prolong the QTcF interval, and no clinically relevant electrocardiogram or vital sign changes were observed in healthy subjects.

scholarly journals Evaluation of the Effect of Contezolid (MRX-I) on the Corrected QT Interval in a Randomized, Double-Blind, Placebo- and Positive-Controlled Crossover Study in Healthy Chinese Volunteers

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Junzhen Wu ◽  
Guoying Cao ◽  
Hailan Wu ◽  
Yuancheng Chen ◽  
Beining Guo ◽  
...  
Keyword(s):  
Therapeutic Dose ◽  
Qt Interval ◽  
Qtc Interval ◽  
Double Blind ◽  
Assay Sensitivity ◽  
Supratherapeutic Dose ◽  
Qt Interval Prolongation ◽  
Point Analysis ◽  
Complicated Skin ◽  
Time Point

ABSTRACT Contezolid (MRX-I), a new oxazolidinone, is an antibiotic in development for treating complicated skin and soft tissue infections caused by resistant Gram-positive bacteria. This was a thorough QT study conducted in 52 healthy subjects who were administered oral contezolid at a therapeutic (800 mg) dose, a supratherapeutic (1,600 mg) dose, placebo, and oral moxifloxacin at 400 mg in four separate treatment periods. The pharmacokinetic profile of contezolid was also evaluated. Time point analysis indicated that the upper bounds of the two-sided 90% confidence interval (CI) for placebo-corrected change-from-baseline QTc (ΔΔQTc) were <10 ms for the contezolid therapeutic dose at each time point. The upper bound of the 90% CI for ΔΔQTc was slightly more than 10 ms with the contezolid supratherapeutic dose at 3 and 4 h postdose, and the prolongation effect on the QT/QTc interval was less than that of the positive control, moxifloxacin, at 400 mg. At 3 and 4 h after the moxifloxacin dose, the moxifloxacin group met the assay sensitivity criteria outlined in ICH Guidance E14 by having a lower confidence bound of ≥5 ms. The results of a linear exposure-response model which were similar to that of a time point analysis demonstrated a slightly positive relationship between contezolid plasma levels and ΔQTcF interval with a slope of 0.227 ms per mg/liter (90% CI, 0.188 to 0.266). In summary, contezolid did not prolong the QT interval at a therapeutic dose and may have a slight effect on QT interval prolongation at a supratherapeutic dose.

Raltegravir Thorough QT/QTc Study: A Single Supratherapeutic Dose of Raltegravir Does Not Prolong the QTcF Interval

2008 ◽  
Vol 48 (6) ◽  
pp. 726-733 ◽  
Author(s):  
M. Iwamoto ◽  
J. T. Kost ◽  
G. C. Misty ◽  
L. A. Wenning ◽  
S. A. Breidinger ◽  
...  
Keyword(s):  
Supratherapeutic Dose

A Single Supratherapeutic Dose of Rolofylline Does Not Prolong the QTcF Interval in Healthy Volunteers

2010 ◽  
Vol 17 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Waldemar Radziszewski ◽  
Eseng Lai ◽  
Nicole Lazarus Shipitofsky ◽  
Mark Stroh ◽  
Victor Dishy ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Supratherapeutic Dose

Thorough QTc Study of a Single Supratherapeutic Dose of Relebactam in Healthy Participants

2020 ◽  
Vol 9 (4) ◽  
pp. 466-475
Author(s):  
Keith Boundy ◽  
Yang Liu ◽  
Pratik Bhagunde ◽  
Terry E. O'Reilly ◽  
Francheska Colon-Gonzalez ◽  
...  
Keyword(s):  
Supratherapeutic Dose ◽  
Healthy Participants
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