Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers

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 a...

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Autores principales:	Jörg Täubel, Ulrike Lorch, Christopher S. Spencer, Anne Freier, Dorothée Camilleri, Dilshat Djumanov, Georg Ferber, Line Marchand, Jean-Pierre Gotteland, Oliver Pohl
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/941c758ff82c46db9ab0bd9fda565dc9
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spelling	oai:doaj.org-article:941c758ff82c46db9ab0bd9fda565dc92021-12-02T11:39:43ZConfirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers10.1038/s41598-021-85650-32045-2322https://doaj.org/article/941c758ff82c46db9ab0bd9fda565dc92021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85650-3https://doaj.org/toc/2045-2322Abstract 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.Jörg TäubelUlrike LorchChristopher S. SpencerAnne FreierDorothée CamilleriDilshat DjumanovGeorg FerberLine MarchandJean-Pierre GottelandOliver PohlNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jörg Täubel Ulrike Lorch Christopher S. Spencer Anne Freier Dorothée Camilleri Dilshat Djumanov Georg Ferber Line Marchand Jean-Pierre Gotteland Oliver Pohl Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers
description	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.
format	article
author	Jörg Täubel Ulrike Lorch Christopher S. Spencer Anne Freier Dorothée Camilleri Dilshat Djumanov Georg Ferber Line Marchand Jean-Pierre Gotteland Oliver Pohl
author_facet	Jörg Täubel Ulrike Lorch Christopher S. Spencer Anne Freier Dorothée Camilleri Dilshat Djumanov Georg Ferber Line Marchand Jean-Pierre Gotteland Oliver Pohl
author_sort	Jörg Täubel
title	Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers
title_short	Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers
title_full	Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers
title_fullStr	Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers
title_full_unstemmed	Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers
title_sort	confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/941c758ff82c46db9ab0bd9fda565dc9
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Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers

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