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

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Bakker C, van der Aart J, Hart EP, Klaassen ES, Bergmann KR, van Esdonk MJ, Kay DG, Groeneveld GJ

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

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

PubMed ID

33083515 [ View in PubMed

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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 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.