title: A 6-week randomized, double-blind, placebo-controlled, comparator referenced trial of vabicaserin in acute schizophrenia.
abstract: Vabicaserin, a potent 5-HT2C receptor agonist, decreases nucleus accumbens extracellular dopamine levels in rats, without affecting striatal dopamine, indicating mesolimbic selectivity. This is the first study of efficacy, safety and tolerability of vabicaserin in adults with acute schizophrenia. Three hundred fourteen hospitalized subjects were randomized to: Vabicaserin 200 or 400 mg/day, olanzapine 15 mg/day or placebo. Central raters assessed the PANSS and CGI-S. Site raters performed the BPRS and CGI-I. Central rated PANSS Positive (PANSS-PPS) was the primary endpoint. Two hundred eighty-nine subjects were included in the mITT efficacy analysis. Vabicaserin was well tolerated with no major safety concerns. Olanzapine, but not vabicaserin, caused weight gain. Vabicaserin 200 mg/day and olanzapine demonstrated significant improvement at week 6 vs. placebo on PANSS-PSS. A non-significant decrease vs. placebo was observed for 400 mg/day. Both vabicaserin groups demonstrated significant improvement over baseline on PANSS Negative while placebo worsened. Vabicaserin 200 mg/day and olanzapine demonstrated significantly greater improvement over placebo on PANSS Total whereas 400 mg/day showed a trend toward improvement. There was no significant improvement vs. placebo for either vabicaserin group on site-rated BPRS. Vabicaserin 200 mg/day and olanzapine demonstrated significant improvement vs. placebo on CGI-I and CGI-S but not 400 mg/day vabicaserin. Vabicaserin demonstrated efficacy on primary and secondary endpoints at 200 mg/day, but not at 400 mg/day which showed a trend for efficacy. The 200 mg/day vabicaserin group achieved proof of concept using central ratings. Both vabicaserin doses were well tolerated with no significant safety signals and no weight gain.
  
  
  BACKGROUND
  clinicaltrials.gov. Identifier: NCT00265551.
authors.affiliation: Hengrui Medicine Co., Ltd, Shanghai, China.
authors.forename: Joan H Q
authors.initials: JH
authors.lastname: Shen
authors.affiliation: Skyview Research, Pennsylvania, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: IVS Pharma Consulting, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Rosenzweig-Lipson
authors.affiliation: MedAvante Inc, Hamilton, NJ, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Popp
authors.affiliation: MedAvante Inc, Hamilton, NJ, USA; College of Physicians and Surgeons, Columbia University, USA. Electronic address: jwilliams@medavante.com.
authors.forename: Janet B W
authors.initials: JB
authors.lastname: Williams
authors.affiliation: MedAvante Inc, Hamilton, NJ, USA.
authors.forename: Earl
authors.initials: E
authors.lastname: Giller
authors.affiliation: Detke Biopharma Consulting LLC, Carmel, IN, USA; Indiana University School of Medicine, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Detke
authors.affiliation: The Zucker Hillside Hospital, Glen Oaks, NY, USA; The Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
mesh_terms: D000208:Acute Disease; D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; C556517:vabicaserin
keywords: Central rater; Clinical trial; Olanzapine; Placebo; Schizophrenia; Vabicaserin