Cariprazine in Negative Symptoms of Schizophrenia: Post-hoc Analyses of a Fixed-dose Phase Iii, Randomized, Double-blind, Placebo- and Active-controlled Trial

Abstract

Introduction

Cariprazine, a dopamine D₃/D₂ receptor partial agonist with preferential binding to D₃ receptors, is being developed for the treatment of schizophrenia

Objective

To explore the effect of cariprazine on negative symptoms of schizophrenia.

Methods

Subjects aged 18-60 years with acute schizophrenia, current acute episode >2 weeks, and a PANSS total score ≥80 and ≤120 were randomly allocated in a 6-Week study NCT01104766 to cariprazine 3 mg/d, cariprazine 6 mg/d, aripiprazole 10 mg/d (active control), or placebo [1]. Post–hoc analyses were performed on subjects with severe negative symptoms and low-to-moderate positive symptoms, defined according to Marder.

Results of the Post-Hoc Analyses

Data of 26 subjects were included in the cariprazine 3 mg/d (17.2% of the total sample), 34 in the cariprazine 6 mg/d (22.1%), 35 in the aripiprazole (23.3%) and 35 in the placebo (23.5%) groups, respectively. Change from baseline to Week 6 in the PANSS Factor Score for Negative Symptoms (PFSNS) was statistically significant for cariprazine 6 mg/d versus placebo (least squares mean difference: cariprazine 3 mg/d=-2.15, p= 0.20; cariprazine 6 mg/d = −3.68, p=.019). Cariprazine 6 mg/d was superior to placebo at each weekly assessment from Week 3. The changes in PFSNS for aripiprazole were not statistically significant at any weekly assessment.

Conclusion

Post–hoc analyses performed on subjects with acute schizophrenia, high level of negative symptoms and low-to-moderate positive symptoms, showed that the patients in the cariprazine 6 mg/d group had a significantly greater improvement relative to placebo on the PFSNS.