A multicenter, randomized, placebo controlled, multiple-dose, safety and pharmacokinetic study of AIT-082 (Neotrofink) in mild Alzheimer’s disease patients M. Grundman a, * , E. Capparelli b , H.T. Kim a , J.C. Morris c , M. Farlow d , E.H. Rubin e , J. Heidebrink f , A. Hake d , G. Ho a , A.N. Schultz a , K. Schafer a , W. Houston a , R. Thomas a , L.J. Thal a and the Alzheimer’s Disease Cooperative Study a Department of Neurosciences, University of California-San Diego, 9500 Gilman, La Jolla, CA 92093, USA b Department of Pediatrics, University of California-San Diego, 9500 Gilman, La Jolla, CA 92093, USA c Department of Neurology, Washington University, School of Medicine, 4488 Forest Park Avenue, St. Louis, MO 63108, USA d Department of Neurology, Indiana University School of Medicine, Emerson Hall, Room 125, Barnhill Drive, Indianapolis, IN 46202-5111, USA e Department of Psychiatry, Washington University, School of Medicine, 4488 Forest Park Avenue, St. Louis, MO 63108, USA f Department of Neurology, University of Michigan Health System, A. Alfred Taubman Health Care Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0322, USA Received 7 June 2002; accepted 23 January 2003 Abstract A phase 1, randomized, double-blind, placebo-controlled, dose escalation study of the purine derivative, AIT- 082 (Neotrofink, 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 0024-3205/03/$ - see front matter D 2003 Elsevier Science Inc. All rights reserved. doi:10.1016/S0024-3205(03)00320-5 * Corresponding author. Department of Neurosciences, University of California, San Diego, 8950 Villa La Jolla Drive, Suite 2200, La Jolla, CA 92037, USA. Tel.: +1-858-622-5827; fax: +1-858-452-3058. E-mail address: mgrundman@ucsd.edu (M. Grundman). www.elsevier.com/locate/lifescie Life Sciences 73 (2003) 539 – 553