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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorSimon, Marc
dc.contributor.authorHanrott, Kate
dc.contributor.authorBudd, David C
dc.contributor.authorTorres, Fernando
dc.contributor.authorGrünig, Ekkehard
dc.contributor.authorEscribano‐Subias, Pilar
dc.contributor.authorLópez Meseguer, Manuel
dc.date.accessioned2022-09-09T13:01:05Z
dc.date.available2022-09-09T13:01:05Z
dc.date.issued2022-01
dc.identifier.citationSimon MA, Hanrott K, Budd DC, Torres F, Grünig E, Escribano-Subias P, et al. An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension. Pulm Circ. 2022 Jan;12(1):e12024.
dc.identifier.issn2045-8940
dc.identifier.urihttp://hdl.handle.net/11351/8122
dc.descriptionArterial hypertension; Hemodynamics; Renin‐angiotensin system
dc.description.abstractPreclinical and early clinical studies suggest that angiotensin-converting enzyme type 2 activity may be impaired in patients with pulmonary arterial hypertension (PAH); therefore, administration of exogenous angiotensin-converting enzyme type 2 (ACE2) may be beneficial. This Phase IIa, multi-center, open-label, exploratory, single-dose, dose-escalation study (NCT03177603) assessed the potential vasodilatory effects of single doses of GSK2586881 (a recombinant human ACE2) on acute cardiopulmonary hemodynamics in hemodynamically stable adults with documented PAH who were receiving background PAH therapy. Successive cohorts of participants were administered a single intravenous dose of GSK2586881 of 0.1, 0.2, 0.4, or 0.8 mg/kg. Dose escalation occurred after four or more participants per cohort were dosed and a review of safety, tolerability, pharmacokinetics, and hemodynamic data up to 24 h postdose was undertaken. The primary endpoint was a change in cardiopulmonary hemodynamics (pulmonary vascular resistance, cardiac index, and mean pulmonary artery pressure) from baseline. Secondary/exploratory objectives included safety and tolerability, effect on renin-angiotensin system peptides, and pharmacokinetics. GSK2586881 demonstrated no consistent or sustained effect on acute cardiopulmonary hemodynamics in participants with PAH receiving background PAH therapy (N = 23). All doses of GSK2586881 were well tolerated. GSK2586881 was quantifiable in plasma for up to 4 h poststart of infusion in all participants and caused a consistent and sustained reduction in angiotensin II and a corresponding increase in angiotensin (1–7) and angiotensin (1–5). While there does not appear to be a consistent acute vasodilatory response to single doses of GSK2586881 in participants with PAH, the potential benefits in terms of chronic vascular remodeling remain to be determined.
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofseriesPulmonary Circulation;12(1)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectHipertensió pulmonar - Tractament
dc.subjectFarmacocinètica
dc.subjectAvaluació de resultats (Assistència sanitària)
dc.subject.meshHypertension, Pulmonary
dc.subject.mesh/drug therapy
dc.subject.meshPharmacokinetics
dc.subject.meshTreatment Outcome
dc.titleAn open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1002/pul2.12024
dc.subject.decshipertensión pulmonar
dc.subject.decs/farmacoterapia
dc.subject.decsfarmacocinética
dc.subject.decsresultado del tratamiento
dc.relation.publishversionhttps://doi.org/10.1002/pul2.12024
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Simon MA] Division of Cardiology, Department of Medicine, University of California, San Francisco, California, USA. [Hanrott K, Budd DC] Research and Development, Medicines Research Centre, GlaxoSmithKline plc., Stevenage, UK. [Torres F] UT Southwestern Medical Center, Dallas, Texas, USA. [Grünig E] Centre for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, Heidelberg, Germany. [Escribano-Subias P] CIBER‐CV Cardiology Department, Pulmonary Hypertension Unit, Hospital Universitario 12 de Octubre, Madrid, Spain. [Meseguer ML] Unitat de Pneumologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid35506108
dc.identifier.wos000773552900001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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