Phase 3 Trial of Cariprazine for Schizophrenia

San Francisco—After 9 weeks of treatment, patients with schizophrenia who received 3 mg or 6 mg of cariprazine had significant improvements in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions-Severity (CGI-S) scale score compared with a placebo group, according to an international, multicenter, double-blind study.

Results were presented during a poster session at the APA meeting. The poster was titled Cariprazine in Acute Exacerbation of Schizophrenia: A Fixed-Dose Phase III, Randomized, Double-Blind, Placebo-, and Active-Controlled Trial.

The authors noted that patients with schizophrenia experience positive, negative, cognitive, and mood symptoms. Although second-generation antipsychotics are effective, patients typically fail to respond to or tolerate initial pharmacologic therapy. For example, according to the Clinical Antipsychotics Trials of Intervention Effectiveness schizophrenia study, 64% to 84% of patients discontinued various antipsychotic medications.

In November 2012, Forest Laboratories, Inc. filed a new drug application to the FDA for the approval of cariprazine, an oral D₃/D₂ receptor partial agonist. The FDA is scheduled to decide whether to approve cariprazine by the end of this year.

This trial began with a washout period of up to 7 days, continued with a 6-week double-blind treatment, and ended with a 2-week safety follow-up. The 617 patients were randomized in a 1:1:1:1 ratio to receive placebo, 3 mg of cariprazine, 6 mg of cariprazine, or 10 mg of aripiprazole per day. Aripiprazole, an atypical antipsychotic, is FDA-approved to treat schizophrenia.

Patients were included if they were 18 to 60 years of age, had schizophrenia, had a current psychotic episode lasting up to 2 weeks, had a PANSS total score between 80 and 120, and had a CGI-S score of 4 or greater. They were excluded if they were experiencing their first episode of psychosis, were at an imminent risk of injuring themselves or others, were at a risk of committing suicide, or had schizoaffective disorder, bipolar I or II, dementia, or other cognitive disorders.

There were no statistically significant differences in the groups based on demographics, baseline characteristics, or disease history. At baseline, mean age was 38 years, 63% of patients were male, and 65% were white.

Compared with the placebo group, each of the 3 other groups had significant improvements in the PANSS Positive and Negative subscales, the 16-item Negative Symptom Assessment (NSA) total score, the NSA Global Negative Symptom Rating, the CGI-S, overall disease state, and quality of life measures. The significant improvement in PANSS total score was evident as early as week 1 in the 6-mg cariprazine group and week 3 for the 3-mg cariprazine group.

Treatment with cariprazine was generally well tolerated, according to the authors. During the double-blind period, serious adverse events were found in 2 patients in the placebo group, 2 patients in the 3-mg cariprazine group, 6 patients in the 6-mg cariprazine group, and 4 patients in the aripiprazole group. There were 2 deaths in the study, both in the
6-mg cariprazine group (suicide and ischemic stroke/myocardial infarction). The authors said neither death was related to cariprazine treatment.

During the safety follow-up period, there were 4 newly emergent adverse events in the placebo group and 5 in each of the cariprazine groups.

This study was supported by Forest Laboratories, Inc. and Gedeon Richter Plc.