Matches in SemOpenAlex for { <https://semopenalex.org/work/W4367369597> ?p ?o ?g. }
- W4367369597 endingPage "1395" @default.
- W4367369597 startingPage "1381" @default.
- W4367369597 abstract "Abstract Soluble guanylate cyclase (sGC) and its product, cyclic guanosine monophosphate, play a role in learning and memory formation. Zagociguat (CY6463) is a novel stimulator of sGC being developed for the treatment of neurodegenerative disease. Single zagociguat doses of 0.3, 1, 3, 10, 20, 30, and 50 mg were administered once to healthy participants in a single‐ascending‐dose phase; then zagociguat 2, 5, 10, and 15 mg was administered q.d. for 14 days in a multiple‐ascending‐dose phase; and, finally, zagociguat 10 mg was administered once in both fed and fasted state in a food‐interaction phase. Safety of zagociguat was evaluated by monitoring treatment‐emergent adverse events, suicide risk, vital signs, electrocardiography, and laboratory tests. Pharmacokinetics of zagociguat were assessed through blood, urine, and cerebrospinal fluid sampling. Pharmacodynamic effects of zagociguat were evaluated with central nervous system (CNS) tests and pharmaco‐electroencephalography. Zagociguat was well‐tolerated across all doses evaluated. Zagociguat exposures increased in a dose‐proportional manner. Median time to maximum concentration ranged from 0.8 to 5 h and mean terminal half‐life from 52.8 to 67.1 h. CNS penetration of the compound was confirmed by cerebrospinal fluid sampling. Zagociguat induced up to 6.1 mmHg reduction in mean systolic and up to 7.5 mmHg reduction in mean diastolic blood pressure. No consistent pharmacodynamic (PD) effects on neurocognitive function were observed. Zagociguat was well‐tolerated, CNS‐penetrant, and demonstrated PD activity consistent with other sGC stimulators. The results of this study support further development of zagociguat." @default.
- W4367369597 created "2023-04-30" @default.
- W4367369597 creator A5016359089 @default.
- W4367369597 creator A5033932552 @default.
- W4367369597 creator A5038645196 @default.
- W4367369597 creator A5041217307 @default.
- W4367369597 creator A5049486515 @default.
- W4367369597 creator A5066805491 @default.
- W4367369597 creator A5082863215 @default.
- W4367369597 creator A5086592805 @default.
- W4367369597 date "2023-05-03" @default.
- W4367369597 modified "2023-09-26" @default.
- W4367369597 title "First‐in‐human trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of zagociguat (CY6463), a CNS‐penetrant soluble guanylyl cyclase stimulator" @default.
- W4367369597 cites W1503855523 @default.
- W4367369597 cites W1952040396 @default.
- W4367369597 cites W1960607431 @default.
- W4367369597 cites W1967275179 @default.
- W4367369597 cites W1971989132 @default.
- W4367369597 cites W1980466924 @default.
- W4367369597 cites W1981265053 @default.
- W4367369597 cites W1984243104 @default.
- W4367369597 cites W1993327975 @default.
- W4367369597 cites W1997023449 @default.
- W4367369597 cites W1999442689 @default.
- W4367369597 cites W2003630942 @default.
- W4367369597 cites W2018983160 @default.
- W4367369597 cites W2024817440 @default.
- W4367369597 cites W2026984392 @default.
- W4367369597 cites W2028655076 @default.
- W4367369597 cites W2043251401 @default.
- W4367369597 cites W2056897135 @default.
- W4367369597 cites W2071421632 @default.
- W4367369597 cites W2090169689 @default.
- W4367369597 cites W2120357670 @default.
- W4367369597 cites W2130236077 @default.
- W4367369597 cites W2131375845 @default.
- W4367369597 cites W2137092180 @default.
- W4367369597 cites W2152299618 @default.
- W4367369597 cites W2165753570 @default.
- W4367369597 cites W2399674801 @default.
- W4367369597 cites W2510030860 @default.
- W4367369597 cites W2514097929 @default.
- W4367369597 cites W2534167499 @default.
- W4367369597 cites W2543174917 @default.
- W4367369597 cites W2594925500 @default.
- W4367369597 cites W2625556521 @default.
- W4367369597 cites W2743952588 @default.
- W4367369597 cites W2744464165 @default.
- W4367369597 cites W2776746197 @default.
- W4367369597 cites W2810776909 @default.
- W4367369597 cites W2898352545 @default.
- W4367369597 cites W2913131772 @default.
- W4367369597 cites W2953428722 @default.
- W4367369597 cites W3001964375 @default.
- W4367369597 cites W3036185152 @default.
- W4367369597 cites W3096425772 @default.
- W4367369597 cites W3120416669 @default.
- W4367369597 cites W3164469098 @default.
- W4367369597 cites W3199368172 @default.
- W4367369597 cites W3203961952 @default.
- W4367369597 cites W4367369597 @default.
- W4367369597 doi "https://doi.org/10.1111/cts.13537" @default.
- W4367369597 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37118895" @default.
- W4367369597 hasPublicationYear "2023" @default.
- W4367369597 type Work @default.
- W4367369597 citedByCount "2" @default.
- W4367369597 countsByYear W43673695972023 @default.
- W4367369597 crossrefType "journal-article" @default.
- W4367369597 hasAuthorship W4367369597A5016359089 @default.
- W4367369597 hasAuthorship W4367369597A5033932552 @default.
- W4367369597 hasAuthorship W4367369597A5038645196 @default.
- W4367369597 hasAuthorship W4367369597A5041217307 @default.
- W4367369597 hasAuthorship W4367369597A5049486515 @default.
- W4367369597 hasAuthorship W4367369597A5066805491 @default.
- W4367369597 hasAuthorship W4367369597A5082863215 @default.
- W4367369597 hasAuthorship W4367369597A5086592805 @default.
- W4367369597 hasBestOaLocation W43673695971 @default.
- W4367369597 hasConcept C111113717 @default.
- W4367369597 hasConcept C112705442 @default.
- W4367369597 hasConcept C126322002 @default.
- W4367369597 hasConcept C173803235 @default.
- W4367369597 hasConcept C197934379 @default.
- W4367369597 hasConcept C2776190711 @default.
- W4367369597 hasConcept C2778375690 @default.
- W4367369597 hasConcept C2778827303 @default.
- W4367369597 hasConcept C2780035454 @default.
- W4367369597 hasConcept C2988731192 @default.
- W4367369597 hasConcept C42219234 @default.
- W4367369597 hasConcept C519581460 @default.
- W4367369597 hasConcept C71924100 @default.
- W4367369597 hasConcept C98274493 @default.
- W4367369597 hasConceptScore W4367369597C111113717 @default.
- W4367369597 hasConceptScore W4367369597C112705442 @default.
- W4367369597 hasConceptScore W4367369597C126322002 @default.
- W4367369597 hasConceptScore W4367369597C173803235 @default.
- W4367369597 hasConceptScore W4367369597C197934379 @default.
- W4367369597 hasConceptScore W4367369597C2776190711 @default.
- W4367369597 hasConceptScore W4367369597C2778375690 @default.