title: A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease.
abstract: OBJECTIVE
  This randomized, double-blind, placebo-controlled, dose-ranging phase 2 study explored safety, efficacy, and biomarker effects of ELND005 (an oral amyloid anti-aggregation agent) in mild to moderate Alzheimer disease (AD).
  
  
  METHODS
  A total of 353 patients were randomized to ELND005 (250, 1,000, or 2,000 mg) or placebo twice daily for 78 weeks. Coprimary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The primary analysis compared 250 mg (n =84) to placebo (n =82) after an imbalance of infections and deaths led to early discontinuation of the 2 higher dose groups.
  
  
  RESULTS
  The 250 mg dose demonstrated acceptable safety. The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL. Brain ventricular volume showed a small but significant increase in the overall 250 mg group (p =0.049). At the 250 mg dose, scyllo-inositol concentrations increased in CSF and brain and CSF Aβx-42 was decreased significantly compared to placebo (p =0.009).
  
  
  CONCLUSIONS
  Primary clinical efficacy outcomes were not significant. The safety and CSF biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD.
  
  
  METHODS
  Due to the small sample sizes, this Class II trial provides insufficient evidence to support or refute a benefit of ELND005.
authors.affiliation: Neurology and the Memory and Aging Program, Butler Hospital, 345 Blackstone Boulevard, Providence, RI 02906, USA. SSalloway@Butler.org
authors.forename: S
authors.initials: S
authors.lastname: Salloway
authors.forename: R
authors.initials: R
authors.lastname: Sperling
authors.forename: R
authors.initials: R
authors.lastname: Keren
authors.forename: A P
authors.initials: AP
authors.lastname: Porsteinsson
authors.forename: C H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: P N
authors.initials: PN
authors.lastname: Tariot
authors.forename: S
authors.initials: S
authors.lastname: Gilman
authors.forename: D
authors.initials: D
authors.lastname: Arnold
authors.forename: S
authors.initials: S
authors.lastname: Abushakra
authors.forename: C
authors.initials: C
authors.lastname: Hernandez
authors.forename: G
authors.initials: G
authors.lastname: Crans
authors.forename: E
authors.initials: E
authors.lastname: Liang
authors.forename: G
authors.initials: G
authors.lastname: Quinn
authors.forename: M
authors.initials: M
authors.lastname: Bairu
authors.forename: A
authors.initials: A
authors.lastname: Pastrak
authors.forename: J M
authors.initials: JM
authors.lastname: Cedarbaum
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007294:Inositol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C075222:amyloid beta-protein (1-42); C009217:scyllitol; D007294:Inositol