A multicenter, randomized, placebo controlled, multiple-dose, safety and pharmacokinetic study of AIT-082 (Neotrofin) in mild Alzheimer's disease patients

Life Sci. 2003 Jun 20;73(5):539-53. doi: 10.1016/s0024-3205(03)00320-5.

Abstract

A phase 1, randomized, double-blind, placebo-controlled, dose escalation study of the purine derivative, AIT-082 (Neotrofin, NeoTherapeutics) was conducted in mild Alzheimer's disease (AD) patients to evaluate multiple-dose safety, tolerability, and pharmacokinetics. Possible short-term effects of AIT-082 on cognition and memory were preliminarily investigated. AIT-082 is currently being developed as a potential treatment for Alzheimer's disease and other neurological disorders. Pre-clinical studies indicate that AIT-082 has memory enhancing properties, stimulates neuritogenesis and the production of neurotrophic factors. Patients received an oral dose of AIT-082 or placebo daily for one week. Thirty-six AD patients were divided into three dose cohorts; each dose cohort consisted of twelve patients with 8 patients randomized to AIT-082 and 4 to placebo. The 3 doses of AIT-082 evaluated in this study were 100 mg/day, 500 mg/day, and 2,000 mg/day. There were no serious adverse events at any dose and the drug was well tolerated without significant side effects. AIT-082 was orally and rapidly absorbed, resulting in peak serum concentrations within 2 hours with an elimination half-life of approximately 20 hours. Higher doses resulted in corresponding increases in peak concentrations and areas under the curve (AUC). There was an approximate 2-fold accumulation in AIT-082 with daily dosing (as reflected by the AUC) at steady state. There were no significant differences by treatment arm on the clinical or neuropsychological evaluations. AIT-082 was rapidly absorbed by the oral route with a half-life suitable for dosing once or twice daily. No problems with tolerability or safety were found. AIT-082 appears suitable for testing in larger clinical trials for the treatment of AD and other neurologic disorders.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Aged
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology
  • Area Under Curve
  • Cognition / drug effects
  • Female
  • Humans
  • Male
  • Neuropsychological Tests
  • Nootropic Agents / administration & dosage
  • Nootropic Agents / adverse effects
  • Nootropic Agents / blood*
  • Severity of Illness Index
  • United States

Substances

  • Nootropic Agents