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Safety, pharmacokinetics, and pharmacodynamics of Gln-1062, a prodrug of galantamine.

ABSTRACT: 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 Tmax of 0.5 hour [range 0.5-1.0]). Cmax and AUC0-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.

SUBMITTER: Bakker C

PROVIDER: S-EPMC7551138 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Safety, pharmacokinetics, and pharmacodynamics of Gln-1062, a prodrug of galantamine.

Bakker Charlotte C van der Aart Jasper J Hart Ellen P EP Klaassen Erica S ES Bergmann Kirsten R KR van Esdonk Michiel J MJ Kay Denis G DG Groeneveld Geert Jan GJ

Alzheimer's & dementia (New York, N. Y.) 20201013 1

<h4>Introduction</h4>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.<h4>Methods</h4>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. Pha ...[more]

PMID: 33083515

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Dataset Information

Safety, pharmacokinetics, and pharmacodynamics of Gln-1062, a prodrug of galantamine.

Publications

Safety, pharmacokinetics, and pharmacodynamics of Gln-1062, a prodrug of galantamine.

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