Phase 3 Trial for Agitation in Alzheimer’s, Dementia Patients Initiated by Intra-Cellular Therapies

New York City-based Intra-Cellular Therapies has started its ITI-007-201 Phase 3 clinical trial for the treatment of agitation in patients with dementia, including Alzheimer’s disease, following the company’s communication with the U.S. FDA.

Intra-Cellular Therapies Chairman and CEO Dr. Sharon Mates said in a press release she is pleased that ITI-007 is advancing into Phase 3 development to treat dementia-associated behavioral problems “as we continue in our mission to provide improved treatment options to patients suffering from CNS disorders.”

“Agitation associated with dementia imparts considerable distress for patients and burden on their caregivers. Given ITI-007’s unique pharmacology, we believe that its ability to fully occupy serotonin 5-HT2A receptors at low doses, while modestly modulating dopamine D2 and D1 receptors, and inhibit serotonin reuptake will improve a wide range of behavioral disturbances associated with dementia, including agitation,” she said.

“We believe the favorable safety and tolerability profile of ITI-007 observed in other patient populations will translate well into this new therapeutic area to ease suffering and improve quality of life for patients and their families,” Mates added.

ITI-007-201 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy, safety, and tolerability of ITI-007 in patients with a clinical diagnosis of probable Alzheimer’s and clinically significant symptoms of agitation.

Approximately 360 patients will be randomly assigned to receive 9 mg of ITI-007 orally once daily for a period of four weeks, or a placebo. The primary endpoint of the Phase 3 clinical trial of ITI-007 is the assessment of efficacy measured by the Cohen-Mansfield Agitation Inventory – Community version (CMAI-C), a tool that evaluated a drug ability to reduce overall frequency of agitation symptoms.

The main secondary endpoint is the assessment of efficacy as measured by a Clinical Global Impression scale for Severity (CGI-S) of illness. Additional exploratory secondary endpoints include measures of other behavioral disturbances associated with dementia.

The trial includes an interim analysis to assess variability and effect size which will be reviewed by an independent data monitoring committee.

Alzheimer’s disease is a chronic neurodegenerative disease that usually starts slowly and gets worse over time and is the cause of 60 to 70 percent of cases of dementia. Worldwide, 44 million people have Alzheimer’s or a related dementia.  Patients with Alzheimer’s can get anxious or upset easily. They might be restless, unable to sleep, or pace back and forth. This agitation can keep them from a normal day-and-night routine and can be disruptive for their loved ones or caregivers.

ITI-007 possesses a mechanism of action targeting multiple brain systems and may allow a physician to fine-tune the drug’s action in the brain by simple dose adjustments. According to Intra-Cellular, at the lowest doses, ITI-007 has been demonstrated to act primarily as a potent 5-HT2A serotonin receptor antagonist. As the dose is increased, additional benefits are derived from the engagement of additional drug targets, including modest dopamine receptor modulation and modest inhibition of serotonin transporters.