ArticleAnnals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc2015
Detection of QTc effects in small studies--implications for replacing the thorough QT study.
Article in Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05478278 (A Phase 1, Two-Part Study in Healthy Volunteers to Evaluate The Effect of Psilocybin on Cardiac Repolarization and The Effect of Food on Psilocybin Pharmacokinetics), which is not on this map. Cited by 30 papers.
What it found
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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.
A Phase 1, Two-Part Study in Healthy Volunteers to Evaluate The Effect of Psilocybin on Cardiac Repolarization and The Effect of Food on Psilocybin Pharmacokinetics
Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- A Randomized Thorough QT Trial Using Concentration-QT Analysis to Evaluate the Effects of Centanafadine on Cardiac Repolarization.Clinical pharmacology in drug development · 2025Trial
- A phase I thorough QT/QTc study evaluating therapeutic and supratherapeutic doses of avacopan in healthy participants.Clinical and translational science · 2024Trial
- No clinically relevant electrocardiogram effects in a randomized TQT study of single therapeutic/supratherapeutic rimegepant doses in healthy adults.Clinical and translational science · 2024Trial
- 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
- A randomized, single-dose, crossover study of the effects of ulotaront on electrocardiogram intervals in subjects with schizophrenia.Clinical and translational science · 2023Trial
- Evaluation of Deutetrabenazine's Potential to Delay Cardiac Repolarization Using Concentration-QTc Analysis.Clinical pharmacology in drug development · 2023Trial
- The effect of the glucosylceramide synthase inhibitor lucerastat on cardiac repolarization: results from a thorough QT study in healthy subjects.Orphanet journal of rare diseases · 2020Trial
- No QTc Prolongation With Zanubrutinib: Results of Concentration-QTc Analysis From a Thorough QT Study in Healthy Subjects.Clinical and translational science · 2020Trial
- Trial
- Association Between Vomiting and QT Hysteresis: Data from a TQT Study with the Endothelin A Receptor Antagonist Clazosentan.The AAPS journal · 2020Trial
- Assessment of Multi-Ion Channel Block in a Phase I Randomized Study Design: Results of the CiPA Phase I ECG Biomarker Validation Study.Clinical pharmacology and therapeutics · 2019Trial
- Evaluation of the Cardiac Safety of Long-Acting Endectocide Moxidectin in a Randomized Concentration-QT Study.Clinical and translational science · 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
- 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
- Evaluation of the QT effect of a combination of piperaquine and a novel anti-malarial drug candidate OZ439, for the treatment of uncomplicated malaria.British journal of clinical pharmacology · 2015Trial
- Sample size determination for cardiodynamic ECG assessment using the Concentration-QTc analysis method.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- No QTc prolongation with CDK 4/6 inhibitor FCN-437c: results of a concentration-QTc analysis from a dedicated study in adult healthy subjects.Frontiers in pharmacology · 2024Article
- A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development.Journal of pharmacokinetics and pharmacodynamics · 2023Review
- Concentration-QTc analysis with two or more correlated baselines.Journal of pharmacokinetics and pharmacodynamics · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundECG assessment with exposure response analysis applied to data from First-in-Man studies has been proposed to replace the thorough QT study for the detection of small QT effects.
methodsData from five thorough QT studies, three with moxifloxacin, one study with a drug with a large QTc effect (∼25 ms) and one with ketoconazole with a smaller QT effect (∼8 ms) were used. By subsampling, studies with 6-18 subjects on drug and six on placebo were simulated 1000 times per sample size to assess whether small QTc effects using ICH E14 criteria could be excluded and the impact of sample size on the estimate and variability of the slope of the concentration/QTc relation.
resultsWith a sample size of nine or more on drug and six on placebo, the fraction of "false negative studies" was at or below 5% with data from the studies with moxifloxacin and from the drug with a large QTc effect. With the same sample size and no underlying QTc effect (placebo), the fraction of studies in which an effect above 10 ms could be excluded was above 85%. A treatment effect in the linear concentration-effect model resulted in a lower proportion of "false negatives." Sample size had little influence on the average slope estimate of the concentration/QTc relationship.
conclusionsFor drugs with a QTc effect of around 12-14 ms, exposure response analysis applied to First-in-Man studies with careful ECG assessment can be used to replace the through QT study.
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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.