A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers

Abstract PT150, a novel competitive glucocorticoid receptor (GR) antagonist, has proven safe in animal models, healthy volunteers, and people with depression. Our study is the first to investigate PT150’s safety with alcohol use. The primary objective of this study was to evaluate pharmacodynamic in...

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Autores principales:	Claire Morice, Dewleen G. Baker, Marguerite M. Patel, Tracy L. Nolen, Kayla Nowak, Shawn Hirsch, Thomas R. Kosten, Christopher D. Verrico
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e47702aff834151b977af287dc2a85f
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spelling	oai:doaj.org-article:0e47702aff834151b977af287dc2a85f2021-12-02T15:36:13ZA randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers10.1038/s41598-021-88609-62045-2322https://doaj.org/article/0e47702aff834151b977af287dc2a85f2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88609-6https://doaj.org/toc/2045-2322Abstract PT150, a novel competitive glucocorticoid receptor (GR) antagonist, has proven safe in animal models, healthy volunteers, and people with depression. Our study is the first to investigate PT150’s safety with alcohol use. The primary objective of this study was to evaluate pharmacodynamic interactions between ethanol and PT150 in healthy subjects. This single-site, Phase I pilot trial consisted of community-recruited, healthy, alcohol-experienced participants aged 21–64 years. Of 32 participants screened, 11 were enrolled and randomized, one of which withdrew before intervention. PT150 (900 mg/day) was administered orally to all participants for five days. All participants received two beverage challenges on Day 1 (before PT150 administration) and Day 5 (after PT150 administration). On challenge days, they received both alcohol (16% ethanol) and placebo (1% ethanol) beverages in random order. Primary outcomes included breath alcohol level, blood pressure, heart rate, adverse events, and electrocardiogram changes. There were no statistically significant differences in vital signs or estimated blood alcohol concentrations between PT150 non-exposed and exposed groups during the ethanol challenge. There were no clinically significant abnormal electrocardiograms or serious adverse events. These data show that administration of PT150 with concurrent alcohol use is safe and well-tolerated. This study supports a future pharmacokinetic interaction study between PT150 and alcohol. Trial Registration ClinicalTrials.gov Identifier: NCT03548714.Claire MoriceDewleen G. BakerMarguerite M. PatelTracy L. NolenKayla NowakShawn HirschThomas R. KostenChristopher D. VerricoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claire Morice Dewleen G. Baker Marguerite M. Patel Tracy L. Nolen Kayla Nowak Shawn Hirsch Thomas R. Kosten Christopher D. Verrico A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers
description	Abstract PT150, a novel competitive glucocorticoid receptor (GR) antagonist, has proven safe in animal models, healthy volunteers, and people with depression. Our study is the first to investigate PT150’s safety with alcohol use. The primary objective of this study was to evaluate pharmacodynamic interactions between ethanol and PT150 in healthy subjects. This single-site, Phase I pilot trial consisted of community-recruited, healthy, alcohol-experienced participants aged 21–64 years. Of 32 participants screened, 11 were enrolled and randomized, one of which withdrew before intervention. PT150 (900 mg/day) was administered orally to all participants for five days. All participants received two beverage challenges on Day 1 (before PT150 administration) and Day 5 (after PT150 administration). On challenge days, they received both alcohol (16% ethanol) and placebo (1% ethanol) beverages in random order. Primary outcomes included breath alcohol level, blood pressure, heart rate, adverse events, and electrocardiogram changes. There were no statistically significant differences in vital signs or estimated blood alcohol concentrations between PT150 non-exposed and exposed groups during the ethanol challenge. There were no clinically significant abnormal electrocardiograms or serious adverse events. These data show that administration of PT150 with concurrent alcohol use is safe and well-tolerated. This study supports a future pharmacokinetic interaction study between PT150 and alcohol. Trial Registration ClinicalTrials.gov Identifier: NCT03548714.
format	article
author	Claire Morice Dewleen G. Baker Marguerite M. Patel Tracy L. Nolen Kayla Nowak Shawn Hirsch Thomas R. Kosten Christopher D. Verrico
author_facet	Claire Morice Dewleen G. Baker Marguerite M. Patel Tracy L. Nolen Kayla Nowak Shawn Hirsch Thomas R. Kosten Christopher D. Verrico
author_sort	Claire Morice
title	A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers
title_short	A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers
title_full	A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers
title_fullStr	A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers
title_full_unstemmed	A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers
title_sort	randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, pt150, and ethanol in healthy volunteers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0e47702aff834151b977af287dc2a85f
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A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers

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