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.
Publisher Copyright:
© 2016 Society of Biological Psychiatry
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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U2 - 10.1016/j.biopsych.2015.08.026
DO - 10.1016/j.biopsych.2015.08.026
M3 - Article
C2 - 26444072
AN - SCOPUS:84945899431
SN - 0006-3223
VL - 79
SP - 952
EP - 961
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 12
ER -