Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine

INTRODUCTION: Gln‐1062 (MEMOGAIN) is an intranasally administered lipophilic prodrug of galantamine. Based on high brain‐to‐blood concentrations observed in pre‐clinical studies, Gln‐1062 is expected to have superior cognitive efficacy compared to oral galantamine. METHODS: Forty‐eight healthy elder...

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Autores principales: Bakker, Charlotte, van der Aart, Jasper, Hart, Ellen P., Klaassen, Erica S., Bergmann, Kirsten R., van Esdonk, Michiel J., Kay, Denis G., Groeneveld, Geert Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551138/
https://www.ncbi.nlm.nih.gov/pubmed/33083515
http://dx.doi.org/10.1002/trc2.12093
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author Bakker, Charlotte
van der Aart, Jasper
Hart, Ellen P.
Klaassen, Erica S.
Bergmann, Kirsten R.
van Esdonk, Michiel J.
Kay, Denis G.
Groeneveld, Geert Jan
author_facet Bakker, Charlotte
van der Aart, Jasper
Hart, Ellen P.
Klaassen, Erica S.
Bergmann, Kirsten R.
van Esdonk, Michiel J.
Kay, Denis G.
Groeneveld, Geert Jan
author_sort Bakker, Charlotte
collection PubMed
description INTRODUCTION: Gln‐1062 (MEMOGAIN) is an intranasally administered lipophilic prodrug of galantamine. Based on high brain‐to‐blood concentrations observed in pre‐clinical studies, Gln‐1062 is expected to have superior cognitive efficacy compared to oral galantamine. METHODS: Forty‐eight healthy elderly subjects were randomized 12:4 to Gln‐1062 (5.5, 11, or 22 mg, b.i.d., for 7 days) or placebo. Safety, tolerability, pharmacokinetics, and pharmacodynamics were assessed repeatedly. Pharmacokinetics were compared with 16 mg oral galantamine. RESULTS: Gln‐1062 up to 22 mg, b.i.d., was well tolerated. Gln‐1062 plasma concentrations increased immediately following dosing (median T(max) of 0.5 hour [range 0.5‐1.0]). C(max) and AUC(0‐last) increased in a dose‐linear manner over all three dose levels. Gln‐1062 was rapidly cleaved into galantamine. Gln‐1062 significantly improved adaptive tracking (sustained attention) with 1.95% (95% confidence interval [CI] 0.630‐3.279, P = 0.0055) compared to placebo after correction for individual baseline performance. DISCUSSION: Gln‐1062 was considered to be safe and caused fewer gastrointestinal side effects than oral galantamine. Gln‐1062 behaved pharmacokinetically as expected and improved performance on cognitive tests.
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spelling pubmed-75511382020-10-19 Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine Bakker, Charlotte van der Aart, Jasper Hart, Ellen P. Klaassen, Erica S. Bergmann, Kirsten R. van Esdonk, Michiel J. Kay, Denis G. Groeneveld, Geert Jan Alzheimers Dement (N Y) Research Articles INTRODUCTION: Gln‐1062 (MEMOGAIN) is an intranasally administered lipophilic prodrug of galantamine. Based on high brain‐to‐blood concentrations observed in pre‐clinical studies, Gln‐1062 is expected to have superior cognitive efficacy compared to oral galantamine. METHODS: Forty‐eight healthy elderly subjects were randomized 12:4 to Gln‐1062 (5.5, 11, or 22 mg, b.i.d., for 7 days) or placebo. Safety, tolerability, pharmacokinetics, and pharmacodynamics were assessed repeatedly. Pharmacokinetics were compared with 16 mg oral galantamine. RESULTS: Gln‐1062 up to 22 mg, b.i.d., was well tolerated. Gln‐1062 plasma concentrations increased immediately following dosing (median T(max) of 0.5 hour [range 0.5‐1.0]). C(max) and AUC(0‐last) increased in a dose‐linear manner over all three dose levels. Gln‐1062 was rapidly cleaved into galantamine. Gln‐1062 significantly improved adaptive tracking (sustained attention) with 1.95% (95% confidence interval [CI] 0.630‐3.279, P = 0.0055) compared to placebo after correction for individual baseline performance. DISCUSSION: Gln‐1062 was considered to be safe and caused fewer gastrointestinal side effects than oral galantamine. Gln‐1062 behaved pharmacokinetically as expected and improved performance on cognitive tests. John Wiley and Sons Inc. 2020-10-13 /pmc/articles/PMC7551138/ /pubmed/33083515 http://dx.doi.org/10.1002/trc2.12093 Text en © 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Bakker, Charlotte
van der Aart, Jasper
Hart, Ellen P.
Klaassen, Erica S.
Bergmann, Kirsten R.
van Esdonk, Michiel J.
Kay, Denis G.
Groeneveld, Geert Jan
Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine
title Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine
title_full Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine
title_fullStr Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine
title_full_unstemmed Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine
title_short Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine
title_sort safety, pharmacokinetics, and pharmacodynamics of gln‐1062, a prodrug of galantamine
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551138/
https://www.ncbi.nlm.nih.gov/pubmed/33083515
http://dx.doi.org/10.1002/trc2.12093
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