An innovative Phase I population pharmacokinetic approach to investigate the pharmacokinetics of an intranasal fentanyl spray in healthy subjects

2013 ◽  
Vol 51 (06) ◽  
pp. 495-508 ◽  
Author(s):  
Nele Plock ◽  
Axel Facius ◽  
Lene Hartmann ◽  
Sybille Baumann ◽  
Rüdiger Nave
Keyword(s):  
Phase I ◽  
Healthy Subjects ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Approach

scholarly journals Population Pharmacokinetic Model for Intravenous ASN100 in Healthy Subjects

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S529-S529
Author(s):  
Scott A Van Wart ◽  
Christopher Stevens ◽  
Zoltan Magyarics ◽  
Steven A Luperchio ◽  
Paul G Ambrose
Keyword(s):  
Healthy Subjects ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic

scholarly journals A Population Pharmacokinetic Meta‐analysis of Veliparib, a PARP Inhibitor, Across Phase I/II/III Trials in Cancer Patients

2021 ◽  
Author(s):  
Sven Stodtmann ◽  
Silpa Nuthalapati ◽  
Doerthe Eckert ◽  
Sreeneeranj Kasichayanula ◽  
Rujuta Joshi ◽  
...  
Keyword(s):  
Phase I ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Parp Inhibitor ◽  
Population Pharmacokinetic

scholarly journals The Power of Phase I Studies to Detect Clinical Relevant QTc Prolongation: A Resampling Simulation Study

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Georg Ferber ◽  
Ulrike Lorch ◽  
Jörg Täubel
Keyword(s):  
Phase I ◽  
Healthy Subjects ◽  
Sparse Sampling ◽  
Positive Control ◽  
Qtc Prolongation ◽  
False Negatives ◽  
Assay Sensitivity ◽  
Phase I Studies ◽  
Sufficient Power

Concentration-effect (CE) models applied to early clinical QT data from healthy subjects are described in the latest E14 Q&A document as promising analysis to characterise QTc prolongation. The challenges faced if one attempts to replace a TQT study by thorough ECG assessments in Phase I based on CE models are the assurance to obtain sufficient power and the establishment of a substitute for the positive control to show assay sensitivity providing protection against false negatives. To demonstrate that CE models in small studies can reliably predict the absence of an effect on QTc, we investigated the role of some key design features in the power of the analysis. Specifically, the form of the CE model, inclusion of subjects on placebo, and sparse sampling on the performance and power of this analysis were investigated. In this study, the simulations conducted by subsampling subjects from 3 different TQT studies showed that CE model with a treatment effect can be used to exclude small QTc effects. The number of placebo subjects was also shown to increase the power to detect an inactive drug preventing false positives while an effect can be underestimated if time points aroundtmaxare missed.

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