title: A phase I study of AIT-082 in healthy elderly volunteers.
abstract: 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 One subject was withdrawn after the third treatment visit owing to poor venous access.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.
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla 92037, USA. mgrundman@ucsd.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Grundman
authors.forename: Martin
authors.initials: M
authors.lastname: Farlow
authors.forename: Guerry
authors.initials: G
authors.lastname: Peavy
authors.forename: Hyun T
authors.initials: HT
authors.lastname: Kim
authors.forename: Edmund
authors.initials: E
authors.lastname: Capparelli
authors.forename: Arlan N
authors.initials: AN
authors.lastname: Schultz
authors.forename: David P
authors.initials: DP
authors.lastname: Salmon
authors.forename: Steven H
authors.initials: SH
authors.lastname: Ferris
authors.forename: Richard
authors.initials: R
authors.lastname: Mobs
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.forename: Kimberly
authors.initials: K
authors.lastname: Schafer
authors.forename: Karen
authors.initials: K
authors.lastname: Campbell
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Hake
authors.forename: Barbara
authors.initials: B
authors.lastname: Schoos
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Thal
mesh_terms: 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
chemical_list: 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