Skip to main content Accessibility help
×
Home
Hostname: page-component-559fc8cf4f-q7jt5 Total loading time: 0.263 Render date: 2021-03-01T16:34:55.912Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": false, "newCiteModal": false, "newCitedByModal": true }

Article contents

30 Lumateperone (ITI-007) for the Treatment of Schizophrenia: Overview of Placebo-Controlled Clinical Trials and an Open-label Safety Switching Study

Published online by Cambridge University Press:  12 March 2019

Kimberly Vanover
Affiliation:
Intra-Cellular Therapies Inc., New York, NY
Steven Glass
Affiliation:
Intra-Cellular Therapies Inc., New York, NY
Susan Kozauer
Affiliation:
Intra-Cellular Therapies Inc., New York, NY
Jelena Saillard
Affiliation:
Intra-Cellular Therapies Inc., New York, NY
Juan Sanchez
Affiliation:
Intra-Cellular Therapies Inc., New York, NY
Michal Weingart
Affiliation:
Intra-Cellular Therapies Inc., New York, NY
Sharon Mates
Affiliation:
Intra-Cellular Therapies Inc., New York, NY
Andrew Satlin
Affiliation:
Intra-Cellular Therapies Inc., New York, NY
Robert Davis
Affiliation:
Intra-Cellular Therapies Inc., New York, NY
Rights & Permissions[Opens in a new window]

Abstract

Background

Lumateperone is a first-in-class agent in development for schizophrenia that acts synergistically through serotonergic, dopaminergic and glutamatergic systems. Lumateperone is a potent 5-HT2A antagonist, a mesolimbic/mesocortical dopamine phosphoprotein modulator (DPPM) with pre-synaptic partial agonist and post-synaptic antagonist activity at D2, a glutamate GluN2B receptor phosphoprotein modulator with D1-dependent enhancement of both NMDA and AMPA currents via the mTOR protein pathway and an inhibitor of serotonin reuptake.

Methods

Lumateperone was evaluated in 3 controlled clinical trials to evaluate efficacy in patients with acute schizophrenia. The primary endpoint was change from baseline on the PANSS total score compared to placebo. In Study ‘005, 335 patients were randomized to receive ITI-007 60mg or 120mg , risperidone 4mg (active control) or placebo QAM for 4weeks. In Study ‘301, 450 patients were randomized to receive ITI-007 60mg or 40mg , or placebo QAM for 4weeks. In Study ‘302, 696 patients were randomized to receive ITI-007 60mg or 20mg , risperidone 4mg (active control) or placebo QAM for 6weeks. Also, an open-label safety switching study was conducted in which 302 patients with stable schizophrenia were switched from standard-of-care (SOC) antipsychotics and treated for 6weeks with lumateperone QPM and then switched back to SOC.

Results

In Studies ‘005 and ‘301, lumateperone (60mg ITI-007) met the primary endpoint with statistically significant superior efficacy over placebo at Day 28. In Study ‘302, neither dose of lumateperone separated from placebo on the primary endpoint; a high placebo response was observed in this study. Across all 3 efficacy trials, lumateperone improved symptoms of schizophrenia with the same trajectory and same magnitude of improvement from baseline to endpoint on the PANSS total score.

Lumateperone was well-tolerated with a favorable safety profile in all studies. In the two studies with risperidone included as an active control, lumateperone was statistically significantly better than risperidone on key safety and tolerability measures. In the open-label safety switching study statistically significant improvements from SOC were observed in body weight, cardiometabolic and endocrine parameters worsened again when switched back to SOC medication. In this study, symptoms of schizophrenia generally remained stable or improved. Greater improvements were observed in subgroups of patients with elevated symptomatology (comorbid symptoms of depression and those with prominent negative symptoms).

Discussion

Lumateperone represents a novel approach to the treatment of schizophrenia with a favorable safety profile in clinical trials. The lack of cardiometabolic and motor safety issues presents a safety profile differentiated from standard-of-care antipsychotic therapy.

Funding Acknowledgements: Intra-Cellular Therapies, Inc.

Type
Abstracts
Copyright
© Cambridge University Press 2019 

Full text views

Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.

Total number of HTML views: 1
Total number of PDF views: 749 *
View data table for this chart

* Views captured on Cambridge Core between 12th March 2019 - 1st March 2021. This data will be updated every 24 hours.

Access

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

30 Lumateperone (ITI-007) for the Treatment of Schizophrenia: Overview of Placebo-Controlled Clinical Trials and an Open-label Safety Switching Study
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

30 Lumateperone (ITI-007) for the Treatment of Schizophrenia: Overview of Placebo-Controlled Clinical Trials and an Open-label Safety Switching Study
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

30 Lumateperone (ITI-007) for the Treatment of Schizophrenia: Overview of Placebo-Controlled Clinical Trials and an Open-label Safety Switching Study
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *