Jeffrey A Lieberman1, Robert E Davis2, Christoph U Correll3, Donald C Goff4, John M Kane3, Carol A Tamminga5, Sharon Mates6, Kimberly E Vanover7. 1. Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital, New York, New York. 2. Intra-Cellular Therapies, Inc., New York, New York; 3-D Pharmaceutical Consultants, San Diego, California. 3. Department of Psychiatry, Hofstra North Shore Long Island Jewish School of Medicine, Hempstead; Zucker Hillside Hospital Glen Oaks, New York. 4. Department of Psychiatry, New York University Langone Medical Center, New York; Nathan Kline Institute for Psychiatric Research, Orangeburg, New York. 5. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas. 6. Intra-Cellular Therapies, Inc., New York, New York. 7. Intra-Cellular Therapies, Inc., New York, New York. Electronic address: kvanover@intracellulartherapies.com.
Abstract
BACKGROUND: An urgent need exists for new treatments of schizophrenia that are effective against a broad range of symptoms and free of limiting safety issues. ITI-007 is a new molecular entity with a pharmacologic profile that combines dose-related monoamine modulation with phosphorylation of intracellular signaling proteins. METHODS: A phase II randomized, double-blind, placebo-controlled, and active-controlled trial was conducted at eight sites in the United States with randomization of 335 acutely psychotic adults with schizophrenia. ITI-007 (60 mg and 120 mg), placebo, and risperidone, included for assay sensitivity, were evaluated as monotherapy for 4 weeks. The primary outcome measure was the Positive and Negative Syndrome Scale total score, with secondary analyses conducted on symptom subscales. RESULTS:ITI-007 60 mg (p = .017, effect size = .4) and risperidone (p = .013, effect size = .4) demonstrated antipsychotic efficacy superiority over placebo on the primary end point. The results of secondary analyses reflected improvements in negative and depressive symptoms by ITI-007 60 mg. ITI-007 120 mg did not separate from placebo. However, both doses of ITI-007 were well tolerated in this patient population, as evidenced by low discontinuation and adverse event rates, and were associated with a benign metabolic profile as evidenced by significantly lower levels of prolactin, fasting glucose, total cholesterol, and triglycerides than risperidone. CONCLUSIONS: The mechanistically novel investigational drug ITI-007 was effective for the treatment of schizophrenia and comparable with placebo on safety measures in this trial. Secondary analyses indicated that ITI-007 improved negative and depression symptoms and might have expanded therapeutic efficacy in comparison with current antipsychotic drugs.
RCT Entities:
BACKGROUND: An urgent need exists for new treatments of schizophrenia that are effective against a broad range of symptoms and free of limiting safety issues. ITI-007 is a new molecular entity with a pharmacologic profile that combines dose-related monoamine modulation with phosphorylation of intracellular signaling proteins. METHODS: A phase II randomized, double-blind, placebo-controlled, and active-controlled trial was conducted at eight sites in the United States with randomization of 335 acutely psychotic adults with schizophrenia. ITI-007 (60 mg and 120 mg), placebo, and risperidone, included for assay sensitivity, were evaluated as monotherapy for 4 weeks. The primary outcome measure was the Positive and Negative Syndrome Scale total score, with secondary analyses conducted on symptom subscales. RESULTS:ITI-007 60 mg (p = .017, effect size = .4) and risperidone (p = .013, effect size = .4) demonstrated antipsychotic efficacy superiority over placebo on the primary end point. The results of secondary analyses reflected improvements in negative and depressive symptoms by ITI-007 60 mg. ITI-007 120 mg did not separate from placebo. However, both doses of ITI-007 were well tolerated in this patient population, as evidenced by low discontinuation and adverse event rates, and were associated with a benign metabolic profile as evidenced by significantly lower levels of prolactin, fasting glucose, total cholesterol, and triglycerides than risperidone. CONCLUSIONS: The mechanistically novel investigational drug ITI-007 was effective for the treatment of schizophrenia and comparable with placebo on safety measures in this trial. Secondary analyses indicated that ITI-007 improved negative and depression symptoms and might have expanded therapeutic efficacy in comparison with current antipsychotic drugs.
Authors: Kunal Maini; Janice W Hollier; Haley Gould; Victoria Bollich; John John LaForge; Elyse M Cornett; Amber N Edinoff; Adam M Kaye; Alan D Kaye Journal: Health Psychol Res Date: 2021-06-19
Authors: Amber Edinoff; Natalie Wu; Charles deBoisblanc; Catherine Olivia Feltner; Mariah Norder; Vesela Tzoneva; Adam M Kaye; Elyse M Cornett; Alan D Kaye; Omar Viswanath; Ivan Urits Journal: Psychopharmacol Bull Date: 2020-09-14
Authors: Maria S Neumeier; Stephanie Homan; Stefan Vetter; Erich Seifritz; John M Kane; Maximilian Huhn; Stefan Leucht; Philipp Homan Journal: Schizophr Bull Date: 2021-10-21 Impact factor: 7.348