Metabolic profile proves favorable
ITI-007 was considered safe and well tolerated. The side effect profile seen with the 60-mg dose was not significantly different from placebo.
The most common adverse event was sedation/somnolence, reported in 17% of the 60-mg group and in 13% of the placebo arm. Dr. Vanover stressed, however, that these patients were hospitalized “with not a lot to do, so a lot of people were taking naps.” Sedation or somnolence was reported in 32.5% of the ITI-007 120-mg group.
Importantly, ITI-007 given at the lower 60-mg dose showed no difference from placebo on extrapyramidal symptoms (EPS), akathisia, or prolactin levels. Also, no clinically significant changes were found in cardiovascular function noted (no QTc prolongation or sustained increase in heart rate, as is seen with risperidone), and the drug had a favorable weight gain (“little or none”) and metabolic profile.
Phase III studies ongoing
Two phase III clinical trials of ITI-007 are underway. The first will test a 4-week course of ITI-007 40 mg and 60 mg against placebo in 400 inpatients with acutely exacerbated episodes of schizophrenia. The second study, called ITI-007-302, is again using risperidone as an active control and will randomly assign 500 patients with acutely exacerbated episodes of schizophrenia to a 6-week course of ITI-007 20 mg, 60 mg, placebo, or risperidone 4 mg. The primary outcomes for both studies will be the change in mean PANSS total score from baseline.
ITI-007 is a first-in-class molecule that combines potent serotonin 5-hydroxytryptamine2A–receptor antagonism, dopamine receptor phosphoprotein modulation (DPPM), glutamatergic phosphoprotein modulation, and serotonin reuptake inhibition into a single-drug candidate for the treatment of acute and residual schizophrenia.
At low doses, ITI-007 is a very potent serotonin 5-HT2A–receptor antagonist, Dr. Vanover said. The 5-HT2A–receptor antagonism improves sleep quality, enhances antipsychotic and antidepressant activity, and reduces anxiety and hostility. As the dose of ITI-007 is increased, other pharmacological targets are engaged, including the activation of DPPM effects.
Dr. Vanover is a full-time employee of ITI.