title: A randomized, double-blind, placebo-controlled trial of aripiprazole lauroxil in acute exacerbation of schizophrenia.
abstract: OBJECTIVE
  This study evaluated the efficacy, safety, and tolerability of aripiprazole lauroxil, a novel long-acting injectable atypical antipsychotic, for the treatment of schizophrenia.
  
  
  METHODS
  An international multicenter, randomized, double-blind, placebo-controlled trial was conducted between December 2011 and March 2014. Patients (N = 623) aged 18 to 70 years with schizophrenia (DSM-IV-TR criteria), experiencing an acute exacerbation, were randomized in a 1:1:1 ratio to receive gluteal intramuscular injection of aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, or matching placebo once monthly for 12 weeks. The primary efficacy outcome was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to day 85. The Clinical Global Impressions-Improvement scale (CGI-I) score at day 85 was the secondary efficacy outcome. Safety and tolerability were assessed.
  
  
  RESULTS
  The PANSS total score (mean ± standard error [SE]) improved significantly from baseline to day 85 in the aripiprazole lauroxil 441 mg and 882 mg groups, with placebo-adjusted differences of -10.9 ± 1.8 (P < .001) and -11.9 ± 1.8 (P < .001), respectively. Significant (P ≤ .004) improvements in both active treatment groups were demonstrated as early as day 8 and continued throughout the treatment period. The proportion of patients who were very much or much improved on the CGI-I was significantly greater with aripiprazole lauroxil 441 mg and 882 mg treatment versus placebo (P < .001). The most common treatment-emergent adverse events were insomnia, akathisia, headache, and anxiety. The incidence of injection site reactions was low, predominantly described as injection site pain, and was associated with the first injection.
  
  
  CONCLUSIONS
  Aripiprazole lauroxil demonstrated robust efficacy for treatment of patients experiencing acute exacerbation of schizophrenia. The improvement in psychotic symptoms was statistically significant and clinically meaningful. Symptom improvement occurred rapidly after initiation of aripiprazole lauroxil treatment and was maintained throughout the study. Both aripiprazole lauroxil 441 mg and 882 mg doses were well tolerated. These results support aripiprazole lauroxil as an important new treatment option for schizophrenia.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01469039; Clinicaltrialsregister.eu identifier: 2012-003445-15.
authors.affiliation: Department of Psychiatry and Physiology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Robert
authors.initials: R
authors.lastname: Risinger
authors.forename: Henry A
authors.initials: HA
authors.lastname: Nasrallah
authors.forename: Yangchun
authors.initials: Y
authors.lastname: Du
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Zummo
authors.forename: Lisa
authors.initials: L
authors.lastname: Corey
authors.forename: Anjana
authors.initials: A
authors.lastname: Bose
authors.forename: Srdjan
authors.initials: S
authors.lastname: Stankovic
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Silverman
authors.forename: Elliot W
authors.initials: EW
authors.lastname: Ehrich
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068180:Aripiprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D000068180:Aripiprazole