Kay DG

References (2)

Title : Safety, pharmacokinetics, and pharmacodynamics of Gln-1062, a prodrug of galantamine - Bakker_2020_Alzheimers.Dement.(N.Y)_6_e12093
Author(s) : Bakker C , van der Aart J , Hart EP , Klaassen ES , Bergmann KR , van Esdonk MJ , Kay DG , Groeneveld GJ
Ref : Alzheimers Dement (N Y) , 6 :e12093 , 2020
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.
ESTHER : Bakker_2020_Alzheimers.Dement.(N.Y)_6_e12093
PubMedSearch : Bakker_2020_Alzheimers.Dement.(N.Y)_6_e12093
PubMedID: 33083515

Title : First in human study with a prodrug of galantamine: Improved benefit-risk ratio? - Baakman_2016_Alzheimers.Dement.(N.Y)_2_13
Author(s) : Baakman AC , t Hart E , Kay DG , Stevens J , Klaassen ES , Maelicke A , Groeneveld GJ
Ref : Alzheimers Dement (N Y) , 2 :13 , 2016
Abstract : INTRODUCTION: Gln-1062 (Memogain) is a pharmacologically inactive prodrug of galantamine. Owing to its lipophilic nature, it preferentially enters the brain, where it is cleaved into active galantamine. Gln-1062 is expected to have fewer peripheral side effects than other cholinesterase inhibitors, with improved effectiveness.
METHODS: This was a double-blind, comparator and placebo-controlled, sequential cohort, single ascending dose study in 58 healthy subjects with Gln-1062 in doses of 5.5, 11, 22, 33, and 44 mg, compared with oral galantamine 16 mg and donepezil 10 mg. Safety, tolerability, pharmacokinetics, and pharmacodynamics were assessed.
RESULTS: Gln-1062 doses up to 33 mg were well tolerated and induced a dose-dependent increase in the plasma concentrations of Gln-1062 and galantamine. Gln-1062 had a dose-dependent positive effect on verbal memory and attention, mainly in the first hours after drug administration. DISCUSSION: Gln-1062 was better tolerated than galantamine in doses with the same molarity and led to improved effects in cognitive tests. This is most likely caused by the more favorable distribution ratio between peripheral and central cholinesterase inhibition. These results give reason for further exploration of this compound.
ESTHER : Baakman_2016_Alzheimers.Dement.(N.Y)_2_13
PubMedSearch : Baakman_2016_Alzheimers.Dement.(N.Y)_2_13
PubMedID: 29067291