Trial reportEuropean journal of clinical pharmacology2015
Establishing assay sensitivity in QT studies: experience with the use of moxifloxacin in an early phase clinical pharmacology study and comparison with its effect in a thorough QT study.
Trial report in European journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed.
- Population pharmacokinetic/pharmacodynamic modeling of nifekalant injection with varies dosing plan in Chinese volunteers: a randomized, blind, placebo-controlled study.Journal of pharmacokinetics and pharmacodynamics · 2024Trial
- Comparing the consistency of electrocardiogram interval measurements by resting ECG versus 12-lead Holter.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2021Trial
- 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
- Association Between Vomiting and QT Hysteresis: Data from a TQT Study with the Endothelin A Receptor Antagonist Clazosentan.The AAPS journal · 2020Trial
- Confirmation of the Cardiac Safety of PGFClinical pharmacology in drug development · 2018Trial
- Estimation of the Power of the Food Effect on QTc to Show Assay Sensitivity.Journal of clinical pharmacology · 2018Trial
- Can an early phase clinical pharmacology study replace a thorough QT study? Experience with a novel H3-receptor antagonist/inverse agonist.European journal of clinical pharmacology · 2016Trial
- Scientific white paper on concentration-QTc modeling.Journal of pharmacokinetics and pharmacodynamics · 2018Review
- Evaluating cardiac risk: exposure response analysis in early clinical drug development.Drug, healthcare and patient safety · 2018Review
- Stability of the Effect of a Standardized Meal on QTc.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2017Article
- Supratherapeutic dose evaluation and effect of lesinurad on cardiac repolarization: a thorough QT/QTc study.Drug design, development and therapy · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo compare the effect of moxifloxacin as a positive control in a single ascending dose (SAD) study with that in a thorough QT (TQT) study.
methodsMoxifloxacin was used as a positive control in a SAD study and a TQT study during the evaluation of the QT liability of a new drug. The SAD study had enrolled 24 males and the TQT study 25 males. Both studies intensively monitored electrocardiograms (ECGs) and pharmacokinetic sampling. Effect of moxifloxacin on QTc interval was analysed in each study by intersection union test (IUT) and by exposure-response (ER) analysis and the results compared. Cost-effectiveness of this approach was computed.
resultsAnalysis by IUT revealed that the maximum mean (90 % confidence interval (CI)) placebo-corrected change from baseline (ΔΔQTcF) in the SAD study and the TQT study were remarkably similar (10.7 (6.5; 14.9) ms vs. 9.09 (6.20; 11.98) ms, respectively). In both studies, assay sensitivity was established by the 90 % lower bound exceeding 5 ms. ER analysis revealed the slopes in both studies to be significantly different from zero and comparable. Bootstrap-predicted effects of moxifloxacin at geometric mean concentrations of ~3000 ng/mL were 8.19 (90 % CI 5.86; 10.7) ms in the SAD study and 7.33 (90 % CI 5.69; 9.70) ms in the TQT study.
conclusionMoxifloxacin can be integrated effectively in a SAD study to establish assay sensitivity, and a TQT study may be replaced by a SAD study which has the required assay sensitivity. Further experience is warranted to verify this conclusion.
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Registered trials
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