title: A double-blind randomized study assessing safety and efficacy following one-year adjunctive treatment with bitopertin, a glycine reuptake inhibitor, in Japanese patients with schizophrenia.
abstract: BACKGROUND
  Bitopertin, a glycine reuptake inhibitor, was investigated as a novel treatment for schizophrenia. We report all the results of a double-blind randomized study assessing safety and efficacy following 52-week adjunctive treatment with bitopertin in Japanese patients with schizophrenia.
  
  
  METHODS
  This study enrolled Japanese outpatients with schizophrenia who met criteria for either "negative symptoms", i.e., patients with persistent, predominant negative symptoms of schizophrenia even after long-term treatment with antipsychotics or "sub-optimally controlled symptoms", i.e., patients with insufficiently improved symptoms of schizophrenia even after long-term treatment with antipsychotics, respectively. One hundred sixty-one patients were randomly assigned to receive 52-week treatments with bitopertin doses of 5, 10, or 20 mg/day at ratio of 1:5:5, where existing antipsychotics were concomitantly administered. Efficacy endpoints included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), and Personal and Social Performance (PSP). The purpose of the present study is primarily to evaluate the safety, and secondarily to investigate the clinical efficacy of bitopertin.
  
  
  RESULTS
  One hundred fourteen patients (71 %) completed 52-week treatment with bitopertin. Most of the adverse events were mild or moderate in their severity. The patients in the 20-mg group experienced more adverse events than the patients in the other two groups. Common dose-dependent adverse events were somnolence and insomnia associated with worsening schizophrenia. The blood hemoglobin levels gradually decreased from baseline in a dose-dependent manner, but there were no patients with the decrease below 10 g/dL that would have led to their discontinuation. All the efficacy endpoints gradually improved in all the treatment groups for both of the two symptoms, while there were no clear differences among the three dose groups.
  
  
  CONCLUSIONS
  Altogether, bitopertin was found to be generally safe and well-tolerated for the treatment of patients with schizophrenia. All three bitopertin treated groups showed improvements in all the efficacy endpoints for both of the two symptoms, i.e., "negative symptoms" and "sub-optimally controlled symptoms", throughout the duration of the study.
  
  
  BACKGROUND
  Japan Pharmaceutical Information Center, number JapicCTI-111627 (registered on September 20, 2011).
authors.affiliation: Department of Psychiatry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirayasu
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan. satosni@chugai-pharm.co.jp.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Sato
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Iida
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Shuto
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Seitaro
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Funatogawa
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Yamada
authors.affiliation: National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Higuchi
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D013450:Sulfones / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C550631:(4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone; D014150:Antipsychotic Agents; D010879:Piperazines; D013450:Sulfones
keywords: Bitopertin; Glycine reuptake inhibitor; NMDA receptor; Schizophrenia