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. 2020 Oct 13;6(1):e12093.
doi: 10.1002/trc2.12093. eCollection 2020.

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

Charlotte Bakker  1 , Jasper van der Aart  1 , Ellen P Hart  1 , Erica S Klaassen  1 , Kirsten R Bergmann  1 , Michiel J van Esdonk  1 , Denis G Kay  2 , Geert Jan Groeneveld  1   3
Affiliations

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

Charlotte Bakker et al. Alzheimers Dement (N Y). .

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.

Keywords: Alzheimer's disease; cholinesterase inhibitor; dementia; galantamine; pharmacodynamics; pharmacokinetics; pharmacology; randomized controlled trial; safety; side effects.

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Conflict of interest statement

This study was funded by Neurodyn Life Sciences Inc., now known as Alpha Cognition Inc. D.G. Kay is employee of Alpha Cognition Inc. All other authors report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
A and B, Plasma concentrations of galantamine cleaved from Gln‐1062 on dosing days 1 and 7 after administration of Gln‐1062 5.5 mg, 11 mg, or 22 mg, b.i.d. C and D, Plasma Gln‐1062 concentrations on dosing days 1 and 7 after administration of Gln‐1062 5.5 mg, 11 mg, or 22 mg, b.i.d.
FIGURE 2
FIGURE 2
Galantamine plasma and CSF concentrations after oral galantamine, dose corrected (left) and 11 mg Gln‐1062 (right). Dots/dotted line = CSF galantamine concentration. Solid line = plasma galantamine concentration
FIGURE 3
FIGURE 3
The change in adaptive tracking test performance (%‐point) from baseline after 22 mg Gln‐1062 on the first and seventh dosing days
See this image and copyright information in PMC

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