A phase I study of AIT-082 in healthy elderly volunteers.
A Phase I, double-blind, placebo-controlled, single-dose, escalation study of the purine derivative, AIT-082 (Neotrofin, NeoTherapeutics, Inc.) was conducted in healthy elderly volunteers. This trial was designed to evaluate single-dose safety, tolerability, and pharmacokinetics. Potential cognitive domains that might benefit from AIT-082 were preliminarily investigated. AIT-082 is currently being developed as a potential treatment for Alzheimer's disease (AD). Preclinical studies indicate that AIT-082 has memory-enhancing properties, stimulates neuritogenesis, and upregulates neurotrophic factors. Subjects received a single oral dose of AIT-082 or placebo on a weekly basis for 5 wk. All patients received a placebo dose at baseline. Six subjects received increasing doses of AIT-082 over the next 4 wk at doses of 0.6, 2.0, 6.0, and 20.0 mg of AIT-082 per kilogram of body weight. Two subjects received placebo throughout the trial. Nine subjects were recruited. One subject was withdrawn after the third treatment visit owing to poor venous access. There were no serious adverse events. The drug was well-tolerated. The time to peak drug concentration was approx 85 min with an elimination half-life of approx 17.6 h. Performance on the Number Comparison, Symbol Digit, and Trails A tests improved with AIT-082 dosing compared to baseline (placebo). In conclusion, AIT-082 was rapidly absorbed by the oral route with a half-life suitable for once daily dosing. No problems with tolerability or safety were demonstrated.
Grundman
Michael
M
Department of Neurosciences, University of California, San Diego, La Jolla 92037, USA. mgrundman@ucsd.edu
Farlow
Martin
M
Peavy
Guerry
G
Kim
Hyun T
HT
Capparelli
Edmund
E
Schultz
Arlan N
AN
Salmon
David P
DP
Ferris
Steven H
SH
Mobs
Richard
R
Thomas
Ronald G
RG
Schafer
Kimberly
K
Campbell
Karen
K
Hake
Ann Marie
AM
Schoos
Barbara
B
Thal
Leon J
LJ
D000368:Aged; D062365:Aminobenzoates; D019540:Area Under Curve; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007042:Hypoxanthines; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D010919:Placebos; D011687:Purines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology
D062365:Aminobenzoates; D007042:Hypoxanthines; D010919:Placebos; D011687:Purines; C086241:4-((3-(1,6-dihyro-6-oxo-9H-purin-9-yl)-1-oxopropyl)amino)benzoic acid