Trial reportBritish journal of pharmacology2016
Detecting moxifloxacin-induced QTc prolongation in thorough QT and early clinical phase studies using a highly automated ECG analysis approach.
Trial report in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes.Clinical research in cardiology : official journal of the German Cardiac Society · 2022Trial
- Randomized, Double-Blind, Placebo- and Positive-Controlled Crossover Study of the Effects of Tebipenem Pivoxil Hydrobromide on QT/QTc Intervals in Healthy Subjects.Antimicrobial agents and chemotherapy · 2021Trial
- Trial
- Elevated Plasma Moxifloxacin Concentrations andAntimicrobial agents and chemotherapy · 2018Trial
- Detecting moxifloxacin-induced QTc prolongation in thorough QT and early clinical phase studies using a highly automated ECG analysis approach.British journal of pharmacology · 2016Trial
- Modeling rotational fluoroquinolone therapy as a novel treatment for ophthalmic MRSA infections.Scientific reports · 2026Article
- Large-Scale Analysis of Age and Sex Effects on Corrected QT and JT Intervals: Insights From Hospital-Based Controls and Moxifloxacin-Treated Cases.Clinical and translational science · 2025Article
- QT Interval Prolongation with One or More QT-Prolonging Agents Used as Part of a Multidrug Regimen for Rifampicin-Resistant Tuberculosis Treatment: Findings from Two Pediatric Studies.Antimicrobial agents and chemotherapy · 2023Observational
- The Effects of Moxifloxacin and Gemifloxacin on the ECG Morphology in Healthy Volunteers: A Phase 1 Randomized Clinical Trial.Diagnostics (Basel, Switzerland) · 2023Article
- Moxifloxacin Pharmacokinetics, Cardiac Safety, and Dosing for the Treatment of Rifampicin-Resistant Tuberculosis in Children.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- A Computational Pipeline to Predict Cardiotoxicity: From the Atom to the Rhythm.Circulation research · 2020Article
- Towards Bridging Translational Gap in Cardiotoxicity Prediction: an Application of Progressive Cardiac Risk Assessment Strategy in TdP Risk Assessment of Moxifloxacin.The AAPS journal · 2018Article
- Evaluating cardiac risk: exposure response analysis in early clinical drug development.Drug, healthcare and patient safety · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeExposure-response (ER) modelling (concentration-QTc analysis) is gaining as much acceptance as the traditional by-time analysis of the placebo-adjusted change from baseline in the QTc interval (ΔΔQTcF). It has been postulated that intensive ECG analysis and ER modelling during early-phase drug development could be a cost-effective approach of estimating QT liability of a new drug, in a small number of subjects. EXPERIMENTAL APPROACH: We used a highly automated analysis of ECGs from 46 subjects from a crossover thorough QT/QTc study to detect ΔΔQTcF with moxifloxacin. Using these data, we also simulated (bootstrapped) 1000 datasets of a parallel study with eight subjects receiving moxifloxacin and eight others receiving placebo. KEY
resultsThe slope from the concentration-QTc analysis for moxifloxacin in 46 subjects was 4.12 ms of ΔΔQTcF per μg(-1) mL(-1) ; at mean Cmax of 2.95 μg·mL(-1) , estimated ΔΔQTcF was 13.4 ms (90% confidence interval 11.3, 15.4 ms). In the 1000 simulated datasets, in 996 datasets, ER modelling showed that the upper bound of the 90% confidence interval for ΔΔQTcF at geometric mean Cmax exceeded 10 ms. In 895 of these 996 datasets, the slope of the ER relationship was statistically significantly positive. Thus, with a small sample size (eight subjects on active drug and eight on placebo), moxifloxacin-induced QTc prolongation was demonstrated using ER analysis with statistical power of >80%. CONCLUSIONS AND IMPLICATIONS: Our study adds to the growing body of data supporting intensive ECG collection and analysis in early-phase studies to estimate QT liability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.