Disappointing results have been reported from the second phase 3 trial of ITI-007, an oral, first-in-class investigational medication for the treatment of patients with schizophrenia. Neither dose of ITI-007 was significantly different from placebo on the study’s primary endpoint––the change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score. The active control, risperidone, did separate from placebo.
ITI-007 20 mg and 60 mg demonstrated reductions from baseline on the PANSS total score of 15.0 points and14.6 points, respectively, compared with a reduction of 15.1 points with placebo. In contrast, risperidone demonstrated a 20.5-point reduction from baseline.
In a press release, the drug’s developer (Intra-Cellular Therapies, Inc.) stated that it believed ITI-007 did not separate from placebo on the prespecified primary endpoint in part because of an unusually high placebo response at certain sites, “which disproportionately affected the trial results and contributed to the efficacy outcome of this study.” The active control arm with risperidone, however, outperformed both the placebo and ITI-007 groups.
Despite the questionable data, Intra-Cellular plans to request a meeting with the FDA’s Division of Psychiatry Products to discuss the regulatory path for ITI-007.
The randomized, double-blind, fixed-dose, placebo- and active-controlled inpatient study was conducted at 13 sites in the United States. A total of 696 patients were randomly assigned to receive ITI-007 (20 mg or 60 mg); risperidone 4 mg as the active control; or placebo once daily in the morning for six weeks. The patients were diagnosed with schizophrenia (using DSM-5 criteria) and were required to have an acute exacerbation of psychotic symptoms. The trial’s primary efficacy measure was the change from baseline compared with placebo at the study endpoint (six weeks) on the PANSS total score.