title: Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease.
abstract: BACKGROUND
  Mibampator, an amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor potentiator, was evaluated for treatment of agitation and aggression (A/A) in Alzheimer's disease (AD).
  
  
  METHODS
  Outpatients (n = 132) with probable AD and A/A randomized to 12 weeks of double-blind treatment with 3-mg po mibampator or placebo were assessed using the 4-domain A/A subscale of the Neuropsychiatric Inventory (NPI-4-A/A) derived from the Neuropsychiatric Inventory. Secondary measures included the Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia, Frontal Systems Behavior Inventory (FrSBe), and Alzheimer's Disease Assessment Scale-Cognitive. Efficacy was analyzed using mixed-effects model repeated measures from baseline to endpoint. Adverse events (AEs), labs, vital signs, and electrocardiograms were monitored.
  
  
  RESULTS
  Baseline characteristics were comparable between groups. Both groups improved on the NPI-4-A/A, but without group differences. Among secondaries, mibampator was significantly better (p = 0.007) than placebo only on the FrSBe. AEs were similar between groups. One death occurred in the placebo group.
  
  
  CONCLUSIONS
  Possible explanations for no significant group differences include caregiver, drug target engagement, and design issues. This trial is registered on ClinicalTrials.gov; ID: NCT00843518.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA. ptt@lilly.com
authors.forename: Paula T
authors.initials: PT
authors.lastname: Trzepacz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cummings
authors.forename: Thomas
authors.initials: T
authors.lastname: Konechnik
authors.forename: Tammy D
authors.initials: TD
authors.lastname: Forrester
authors.forename: Curtis
authors.initials: C
authors.lastname: Chang
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Dennehy
authors.forename: Brian A
authors.initials: BA
authors.lastname: Willis
authors.forename: Catherine
authors.initials: C
authors.lastname: Shuler
authors.forename: Linda B
authors.initials: LB
authors.lastname: Tabas
authors.forename: Constantine
authors.initials: C
authors.lastname: Lyketsos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression / Q000187:drug effects* / Q000523:psychology; D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy / Q000523:psychology; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010045:Outpatients; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D001713:Biphenyl Compounds; C512030:N-((2-(4'-(2-(methylsulfonyl)amino)ethyl)(1,1'-biphenyl)-4-yl)propyl)-2-propanesulfonamide; D013449:Sulfonamides