title: Bitopertin in Negative Symptoms of Schizophrenia-Results From the Phase III FlashLyte and DayLyte Studies.
abstract: There is currently no standard of care for treatment of negative symptoms of schizophrenia, although some previous results with glutamatergic agonists have been promising.
  
  
  
  Three (SunLyte [WN25308], DayLyte [WN25309], and FlashLyte [NN25310]) phase III, multicenter, randomized, 24-week, double-blind, parallel-group, placebo-controlled studies evaluated the efficacy and safety of adjunctive bitopertin in stable patients with persistent predominant negative symptoms of schizophrenia treated with antipsychotics. SunLyte met the prespecified criteria for lack of efficacy and was declared futile. Key inclusion criteria were age ≥18 years, DSM-IV-TR diagnosis of schizophrenia, score ≥40 on the sum of the 14 Positive and Negative Syndrome Scale negative symptoms and disorganized thought factors, unaltered antipsychotic treatment, and clinical stability. Following a 4-week prospective stabilization period, patients were randomly assigned 1:1:1 to bitopertin (5 mg and 10 mg [DayLyte] and 10 mg and 20 mg [FlashLyte]) or placebo once daily for 24 weeks. The primary efficacy end point was mean change from baseline in Positive and Negative Syndrome Scale negative symptom factor score at week 24.
  
  
  
  The intent-to-treat population in DayLyte and FlashLyte included 605 and 594 patients, respectively. At week 24, mean change from baseline showed improvement in all treatment arms but no statistically significant separation from placebo in Positive and Negative Syndrome Scale negative symptom factor score and all other end points. Bitopertin was well tolerated.
  
  
  
  These studies provide no evidence for superior efficacy of adjunctive bitopertin in any of the doses tested over placebo in patients with persistent predominant negative symptoms of schizophrenia.
authors.affiliation: Global Development Team, Basel, Switzerland. Electronic address: Dragana.Bugarski-Kirola@roche.com.
authors.forename: Dragana
authors.initials: D
authors.lastname: Bugarski-Kirola
authors.affiliation: PD Neuroscience, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Blaettler
authors.affiliation: Department of Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, CIBERSAM, Madrid, Spain.
authors.forename: Celso
authors.initials: C
authors.lastname: Arango
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Wolfgang W
authors.initials: WW
authors.lastname: Fleischhacker
authors.affiliation: Neuroscience, and Neuroscience Product Development, Basel, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: Garibaldi
authors.affiliation: Roche (China) Holding Ltd.
authors.forename: Alice
authors.initials: A
authors.lastname: Wang
authors.affiliation: Roche Products Limited.
authors.forename: Mark
authors.initials: M
authors.lastname: Dixon
authors.affiliation: Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, St. Louis, Missouri.
authors.forename: Henry
authors.initials: H
authors.lastname: Nasrallah
authors.affiliation: Department of Psychiatry and Neuro-Imaging, Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lawrie
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Julie
authors.initials: J
authors.lastname: Napieralski
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Tania
authors.initials: T
authors.lastname: Ochi-Lohmann
authors.affiliation: Roche Products Limited.
authors.forename: Carol
authors.initials: C
authors.lastname: Reid
authors.affiliation: Desert Pacific Mental Illness Research, Education, and Clinical Center, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, Los Angeles, California.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Marder
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
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: Adjunctive; Bitopertin; GRI; Glycine reuptake inhibitor; NMDA receptor; Negative symptoms; Schizophrenia