COLORADO SPRINGS, Colorado — An investigational, first-in-class antipsychotic is showing promise as an effective agent in the treatment of schizophrenia, with an improved side effect profile, results from a phase 2 study suggest.

ITI-007 (Intra-Cellular Therapies Inc), a unique, multitasking antipsychotic, was effective and demonstrated reduced motor and metabolic side effects compared with the antipsychotic risperidone (Risperdal, Janssen Pharmaceuticals, Inc).

"This drug has a different pharmacological profile than any of the other antipsychotics," said Kimberly E. Vanover, PhD, an employee of Intra-Cellular Therapies.

"We believe the unique serotonergic-dopaminergic-glutamatergic pharmacological profile represents a new approach to the treatment of schizophrenia in a single stand-alone therapy."

Dr Vanover presented the results here at the 15th International Congress on Schizophrenia Research (ICOSR).

Targets Multiple Symptoms

The drug combines potent serotonin 5-HT2A receptor antagonism, dopamine receptor phosphoprotein modulation, glutamatergic modulation, and serotonin reuptake inhibition, according to Intra- Cellular Therapies.

Symptoms that are targeted include sleep quality and antipsychotic and antidepressant activity. The drug shows some signs of improving social function as well.

Earlier phase 1 and phase 2 trials have shown improvements in areas such as antipsychotic efficacy, sleep maintenance, and a reduction in negative symptoms associated with schizophrenia.

For the new phase 2 study, 335 patients with schizophrenia who had a recent, acutely exacerbated episode were randomly assigned to receive ITI-007 in doses of 60 mg or 120 mg or placebo daily for 4 weeks.

Patients receiving 60 mg achieved the primary endpoint of a statistically significant change from baseline on the Positive and Negative Syndrome Scale (PANSS) at day 28 (P ≤ .05 vs placebo).

Importantly, both the group receiving 60 mg and the group receiving 120 mg showed significantly lower levels of metabolic measures that are increased with the popular antipsychotic drug risperidone, including insulin, glucose, triglyceride, total cholesterol, and LDL cholesterol levels, as well as prolactin levels.

The drug was safe and well tolerated, and the 60-mg dose was no different than placebo with regard to side effects. The most frequent adverse event reported was sedation, which occurred in the group receiving the 120-mg dose.

There were no changes in cardiovascular function, including QTc prolongation, and unlike risperidone, ITI-007 therapy was not associated with an increase in heart rate.

ITI-007 therapy was also associated with a favorable weight gain profile, Dr Vanover said.

Subgroup analyses of patients with comorbid depression at baseline, defined as a score of >6 on the Calgary Depression Scale for Schizophrena, showed robust improvements in total PANSS scores by day 28 in the 60-mg group.

"There was a very robust effect over time in the total PANSS score in this subgroup, with mean improvement of close to 50% in the 60-mg group in this cohort of patients with schizophrenia and depression," she said.

In addition, on the basis of anecdotal reports of patients having noticeable improvements in social activity, the authors performed post hoc subanalysis, using the PANSS-derived prosocial factor evaluation, which consists of measures in positive and negative symptoms, such as emotional withdrawal and active social avoidance.

They found significant improvement, with effect size of 0.6 with ITI-007, compared with an effect size of 0.4.

New Treatment Option?

The results so far suggest that the drug could indeed offer a new option for schizophrenia treatment, Charles Schulz, MD, professor and head of the Department of Psychiatry at the University of Minnesota, in Minneapolis, told Medscape Medical News.

"The trial came across as a potentially important addition to the treatment of schizophrenia, and the activity was described as somewhat similar to clozapine, which is effective without too much dopamine blockade," said Dr Schulz, who moderated the session.

"The weight issues were well described and useful as well, which is an important health area."

"I thought it was an interesting report, and we look forward to seeing if it will indeed be a step ahead," he added.

ITI-007 is currently in phase 3 clinical development for the treatment of schizophrenia.

The study was funded by Intra-Cellular Therapies. Dr Vanover is an employee of the Intra-Cellular Therapies. Dr Schulz reports no relevant financial relationships.

15th International Congress on Schizophrenia Research (ICOSR) Abstract 2191190. Presented March 30, 2015.