ArticleClinical and translational science2019
Models of Variability and Circadian Rhythm in Heart Rate, Blood Pressure, and QT Interval for Healthy Subjects Who Received Placebo in Phase I Trials.
Article in Clinical and translational science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 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.
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, 15 citations in OpenAlex.
- Concentration-QTcF analysis of quizartinib in patients with newly diagnosed FLT3-internal-tandem-duplication-positive acute myeloid leukemia.Clinical and translational science · 2024Trial
- Exposure-safety analysis of QTc interval and transaminase levels following bedaquiline administration in patients with drug-resistant tuberculosis.CPT: pharmacometrics & systems pharmacology · 2021Trial
- PK/PD modeling of a clazosentan thorough QT study with hysteresis in concentration-QT and RR-QT.Journal of pharmacokinetics and pharmacodynamics · 2021Trial
- Exposure-QTc modeling of bedaquiline, pretomanid, and clofazimine in adults with tuberculosis.Antimicrobial agents and chemotherapy · 2026Article
- Risks encountered when not adjusting for diurnal variation and food effect in QTcF analysis based on phase I data.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Beyond the linear model in concentration-QT analysis.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Pooled analysis of routine safety parameters observed in healthy participants at baseline and following placebo administration in early phase clinical studies.Clinical and translational science · 2024Article
- Modeling time-delayed concentration-QT effects with ACT-1014-6470, a novel oral complement factor 5a receptor 1 (C5aPharmacology research & perspectives · 2023Article
- The power of modelling pulsatile profiles.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- The relationship between QT interval indices with cardiac autonomic neuropathy in diabetic patients: a case control study.Diabetology & metabolic syndrome · 2020Article
- Corrigendum to "Models of Variability and Circadian Rhythm in Heart Rate, Blood Pressure, and QT Interval for Healthy Subjects Who Received Placebo in Phase I Trials".Clinical and translational science · 2020Article
- CLOCK-BMAL1 regulates circadian oscillation of ventricular arrhythmias in failing hearts through β1 adrenergic receptor.American journal of translational research · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This work characterized the time-course, circadian rhythm, and inherent variability in key cardiovascular variables (heart rate, corrected QT interval, and systolic and diastolic blood pressure) that are routinely collected as part of safety monitoring in phase I trials. Longitudinal data from 1,035 healthy volunteers who received placebo in 65 single-dose and multiple-dose phase I trials conducted by AbbVie were compiled and analyzed using nonlinear mixed-effects modeling. An independent nonlinear mixed-effects model was developed for each variable, and combinations of cosine functions were used to capture circadian oscillations. Gender, race, age, and body weight were significant covariates for variability in baseline measures, and the contributions of these covariates were quantitatively characterized. Based on the extensive data set analyzed, the developed models represent valuable tools to help contextualize and differentiate inherent variability that can be expected in a typical phase I setting from true drug-related cardiovascular safety signals. In addition, these placebo models can be used to support exposure-response analyses that estimate treatment-related effects on the evaluated cardiovascular measures.
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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.