Dragana Bugarski-Kirola1, Thomas Blaettler2, Celso Arango3, Wolfgang W Fleischhacker4, George Garibaldi5, Alice Wang6, Mark Dixon7, Rodrigo A Bressan8, Henry Nasrallah9, Stephen Lawrie10, Julie Napieralski11, Tania Ochi-Lohmann11, Carol Reid7, Stephen R Marder12. 1. Global Development Team, Basel, Switzerland. Electronic address: Dragana.Bugarski-Kirola@roche.com. 2. PD Neuroscience, Basel, Switzerland. 3. Department of Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, CIBERSAM, Madrid, Spain. 4. Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Innsbruck, Austria. 5. Neuroscience, and Neuroscience Product Development, Basel, Switzerland. 6. Roche (China) Holding Ltd. 7. Roche Products Limited. 8. Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil. 9. Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, St. Louis, Missouri. 10. Department of Psychiatry and Neuro-Imaging, Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. 11. F. Hoffmann-La Roche, Basel, Switzerland. 12. Desert Pacific Mental Illness Research, Education, and Clinical Center, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, Los Angeles, California.
Abstract
BACKGROUND: There is currently no standard of care for treatment of negative symptoms of schizophrenia, although some previous results with glutamatergic agonists have been promising. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: There is currently no standard of care for treatment of negative symptoms of schizophrenia, although some previous results with glutamatergic agonists have been promising. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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