Täubel, J; Lorch, U; Spencer, CS; Freier, A; Camilleri, D; Djumanov, D; Ferber, G; Marchand, L; Gotteland, J-P; Pohl, O
(2021)
Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers.
Sci Rep, 11 (1).
p. 6404.
ISSN 2045-2322
https://doi.org/10.1038/s41598-021-85650-3
SGUL Authors: Taubel, Jorg
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Abstract
Nolasiban is an orally active oxytocin receptor antagonist being developed to increase the efficiency of assisted reproductive technologies. This study evaluated the pharmacokinetics, pharmacodynamics, and cardiac safety of nolasiban in 45 healthy women of child-bearing age. Nolasiban was administered in a fasted state with a standardised lunch served 4.5 h post-dose. Concentration-effect modelling was used to assess the effect of two dosages of nolasiban (900 mg and 1800 mg) on QTc following single-dose administration. We found no significant change in QTc at all tested dosages. Two-sided 90% confidence intervals of geometric mean Cmax for estimated QTc effects of nolasiban were below the threshold of regulatory concern. The sensitivity of the assay to detect small changes in QTc was confirmed by a significant shortening of QTc between 2 and 4 h after consumption of a meal, which served to validate the model. Independent of the nolasiban assessment, this study also explored the effects of sex hormones on ECG parameters, especially QT subintervals. We found a significant relationship between JTpc and oestradiol. Heart rate was negatively correlated with progesterone. This study confirms the cardiovascular safety of nolasiban and describes relationships of sex hormones and ECG parameters.
Item Type: | Article |
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Additional Information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2021 |
Keywords: | Adult, Cohort Studies, Dose-Response Relationship, Drug, Electrocardiography, Female, Healthy Volunteers, Heart, Heart Rate, Humans, Oximes, Pyrrolidines, Receptors, Oxytocin, Reproductive Techniques, Assisted, Young Adult, Heart, Humans, Oximes, Pyrrolidines, Receptors, Oxytocin, Electrocardiography, Reproductive Techniques, Assisted, Cohort Studies, Heart Rate, Dose-Response Relationship, Drug, Adult, Female, Young Adult, Healthy Volunteers |
SGUL Research Institute / Research Centre: | Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: | Sci Rep |
ISSN: | 2045-2322 |
Language: | eng |
Publisher License: | Creative Commons: Attribution 4.0 |
PubMed ID: | 33739022 |
Web of Science ID: | WOS:000667600100019 |
Go to PubMed abstract | |
URI: | https://openaccess.sgul.ac.uk/id/eprint/115596 |
Publisher's version: | https://doi.org/10.1038/s41598-021-85650-3 |
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