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

Abstract

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