Trial reportJournal of pharmacokinetics and pharmacodynamics2012
Moxifloxacin versus placebo modeling of the QT interval.
Trial report in Journal of pharmacokinetics and pharmacodynamics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
11 citing papers in PubMed, 14 citations in OpenAlex.
- Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023Trial
- Assessing QT/QTc interval prolongation with concentration-QT modeling for Phase I studies: impact of computational platforms, model structures and confidence interval calculation methods.Journal of pharmacokinetics and pharmacodynamics · 2018Trial
- Beyond the linear model in concentration-QT analysis.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Evaluation of QT Liability for PF-05251749 in the Presence of Potential Circadian Rhythm Modification.CPT: pharmacometrics & systems pharmacology · 2020Article
- Concentration-QT Modeling Following Inhalation of the Novel Inhaled Phosphodiesterase-4 Inhibitor CHF6001 in Healthy Volunteers Shows an Absence of QT Prolongation.CPT: pharmacometrics & systems pharmacology · 2019Article
- Evaluating cardiac risk: exposure response analysis in early clinical drug development.Drug, healthcare and patient safety · 2018Review
- Estimation of QT interval prolongation through model-averaging.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- Assessment of Interspecies Differences in Drug-Induced QTc Interval Prolongation in Cynomolgus Monkeys, Dogs and Humans.Pharmaceutical research · 2016Article
- Evaluating the Use of Linear Mixed-Effect Models for Inference of the Concentration-QTc Slope Estimate as a Surrogate for a Biological QTc Model.CPT: pharmacometrics & systems pharmacology · 2015Article
- Pharmacokinetic-pharmacodynamic analysis to evaluate the effect of moxifloxacin on QT interval prolongation in healthy Korean male subjects.Drug design, development and therapy · 2015Article
- The role of concentration-effect relationships in the assessment of QTc interval prolongation.British journal of clinical pharmacology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The objectives were to develop a population model for placebo-corrected moxifloxacin QT interval in healthy subjects using non-linear mixed effects modeling and to examine effect of covariates on the observed QT. Based on the parameters of interest, optimizations of observation times and number of subjects were proposed. A pool of four thorough QT studies was used, representing 99 subjects receiving placebo and moxifloxacin. The data was modeled using Monolix. The placebo effect on QT was satisfactorily described using a 2-oscillator model. It reflected the circadian rhythm variability which is taken into account when assessing the time-matched mean difference on QT between treatment and baseline. Based on this model, the moxifloxacin effect on QT was satisfactorily described by the same equation with the adjunct of a direct and proportional drug concentration-effect. The Emax model provided the best description of the effect. The unique covariate was gender for both baseline QTc and individual heart rate correction factor. The present design included up to 16 observations for pharmacodynamics. Using this model, 9 observation times for pharmacodynamics provided satisfactory estimates for the parameters of interest (Emax). With 15% precision limit on Emax, 60 subjects was optimal. The simultaneous placebo-moxifloxacin QT model proposed is an interesting alternative to the ICH E14 guideline in assessing QT prolongation effect. This approach provides accurate information over a range of concentrations using different relationships (slope or Emax models) to quantify the drug-response relationship versus placebo. This allowed optimizing the observation times and number of subjects.
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What OpenQuestion holds
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.