TY - JOUR
T1 - ITI-007 for the Treatment of Schizophrenia
T2 - A 4-Week Randomized, Double-Blind, Controlled Trial
AU - Lieberman, Jeffrey A.
AU - Davis, Robert E.
AU - Correll, Christoph U.
AU - Goff, Donald C.
AU - Kane, John M.
AU - Tamminga, Carol A.
AU - Mates, Sharon
AU - Vanover, Kimberly E.
N1 - Funding Information:
This clinical trial was funded by Intra-Cellular Therapies, Inc. (ITI). ITI-007-005 Phase 2 Study Investigators included J. Aukstuolis, Little Rock, AR; D. Brown, Austin, TX; S. Glass, Marlton, NJ; R. Litman, Rockville, MD; R. Mofsen, St. Louis, MO; M. Novitsky, Philadelphia, PA; R. Riesenberg, Atlanta, GA; and D. Walling, Garden Grove, CA.
Funding Information:
Dr. Lieberman is an unpaid advisor to ITI; reports additional consulting/advising for EnVivo and Pear Therapeutics; has received research grants from Biomarin, EnVivo, Genentech, Lilly, Novartis, Psychogenics, and Sunovion; and holds a patent for Repligen. Dr. Davis is a paid consultant to ITI. Dr. Correll reports financial relationships as a consultant/advisor for Eli Lilly and Company; Genentech, Inc.; Gerson Lehrman Group; ITI; Janssen/Johnson & Johnson; Lundbeck, Inc.; MedAvante; Pfizer, Inc.; ProPhase; Otsuka Pharmaceuticals Co., Ltd.; Roche; Sunovion; Supernus; and Takeda Pharmaceuticals North America, Inc. Dr. Correll has served as a speaker for Bristol-Myers Squibb Company, Janssen/Johnson & Johnson, ProPhase, and Otsuka Pharmaceuticals Co., Ltd. Dr. Correll has received research grants from Bristol-Myers Squibb Company, Novo Nordisk, AstraZeneca Pharmaceuticals LP, and Otsuka Pharmaceuticals Co., Ltd., and served as member of the Data Safety Monitoring Board of Eli Lilly and Company; Cephalon; Janssen; Lundbeck, Inc.; Pfizer, Inc.; and Takeda Pharmaceuticals North America, Inc. Dr. Goff is an unpaid advisor to ITI. Dr. Kane reports consulting fees for Alkermes, Bristol-Myers Squibb, Eli Lilly, Forrest, Forum, Genentech, ITI, Janssen, Johnson and Johnson, Lundbeck, Novartis, Otsuka, Roche, Sunovion, Reviva, and Pierre Fabre. Dr. Tamminga reports having received consulting fees from Astellas, Eli Lilly, ITI, Kay Scholer LLC, Lundbeck, and Pfizer. Drs. Mates and Vanover are full-time employees of ITI.
PY - 2016/6/15
Y1 - 2016/6/15
N2 - 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.
AB - 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.
KW - Antipsychotic
KW - Comorbid depression
KW - Negative symptoms
KW - Positive symptoms
KW - Prosocial factor
KW - Safety
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UR - http://www.scopus.com/inward/citedby.url?scp=84945899431&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2015.08.026
DO - 10.1016/j.biopsych.2015.08.026
M3 - Article
C2 - 26444072
AN - SCOPUS:84945899431
VL - 79
SP - 952
EP - 961
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 12
ER -