ArticleJournal of pharmacokinetics and pharmacodynamics2019
Cardiac risk assessment based on early Phase I data and PK-QTc analysis is concordant with the outcome of thorough QTc trials: an assessment based on eleven drug candidates.
Article in Journal of pharmacokinetics and pharmacodynamics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Effect of hydroxychloroquine on the cardiac ventricular repolarization: A randomized clinical trial.British journal of clinical pharmacology · 2022Trial
- Concentration response analyses for QT data with several active compounds.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- A note on phase I interleaved versus parallel group ascending dose designs for concentration-QTc analyses.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Assessing QTc Effects of Vericiguat Using Two Different Concentration-QTc Modeling Approaches.Clinical pharmacokinetics · 2023Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cardiac safety assessment is a key regulatory requirement for almost all new drugs. Until recently, one evaluation aspect was via a specifically designated, expensive, and resource intensive thorough QTc study, and a by-time-point analysis using an intersection-union test (IUT). ICH E14 Q&A (R3) (http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E14/E14_Q_As_R3__Step4.pdf) allows for analysis of the PK-QTc relationship using early Phase I data to assess QTc liability. In this paper, we compared the cardiac risk assessment based on the early Phase I analysis with that from a thorough QTc study across eleven drug candidate programs, and demonstrate that the conclusions are largely the same. The early Phase I analysis is based upon a linear mixed effect model with known covariance structure (Dosne et al. in Stat Med 36(24):3844-3857, 2017). The treatment effect was evaluated at the supratherapeutic C
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Registered trials
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