Safety, pharmacokinetics, and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers.
This study was designed to determine the safety, tolerability, pharmacokinetics and effects on cognitive function of GTS-21 in healthy, male volunteers. A total of 18 subjects were randomized to GTS-21 (25, 75 and 150 mg) or placebo administered three times daily (first 4 days, once on Day 5) for three, 5-day sessions. GTS-21 was well tolerated up to doses of 450 mg/day, with no clinically significant safety findings. C(max) and the area under the plasma concentration of GTS-21 and the metabolite 4-OH-GTS-21 increased in a dose-related fashion; although considerable intersubject variability occurred, it decreased with continued dosing. GTS-21 showed statistically significant enhancement of three measures of cognitive function (attention, working memory, episodic secondary memory) compared to placebo. A relationship between exposure to GTS-21 and the magnitude of the cognitive response was apparent, with maximal effect approached for doses between 75 and 150 mg three times a day. These data indicate that GTS-21 may represent a novel treatment for dementia.
Kitagawa
Harumi
H
Quintiles, Inc., Tokyo, Japan.
Takenouchi
Toshiharu
T
Azuma
Ryotaro
R
Wesnes
Keith A
KA
Kramer
William G
WG
Clody
Donald E
DE
Burnett
Angela L
AL
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001597:Benzylidene Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics*
D001597:Benzylidene Compounds; D011725:Pyridines; C088936:3-(2,4-dimethoxybenzylidene)anabaseine