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 pharmacological profile that combines dose-related monoamine modulation with phosphorylation of intracellular signaling proteins.
Methods
A phase II randomized, double-blind, placebo- and active-controlled trial was conducted at 8 sites in the US and randomized 335 acutely psychotic adults with schizophrenia. ITI-007 (60 mg, 120 mg), placebo, or risperidone, included for assay sensitivity, was evaluated as monotherapy for 4 weeks. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score, with secondary analyses conducted on symptom subscales.
Results
ITI-007 60 mg (P=0.017, effect size=0.4) and risperidone (P=0.013, effect size=0.4) demonstrated antipsychotic efficacy superiority over placebo on the primary endpoint. 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.
Conclusion
This mechanistically novel investigational drug ITI-007 was effective for the treatment of schizophrenia and comparable to 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 to current antipsychotic drugs.
(ClinicalTrials.gov, NCT01499563
http://www.biologicalpsychiatryjournal.com/article/S0006-3223(15)00694-0/fulltext