Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: a pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies

Cariprazine, a potent dopamine D-3 and D-2 receptor partial agonist antipsychotic with preferential binding to D-3 receptors, is Food and Drug Administration approved for treating schizophrenia and manic or mixed episodes of bipolar I disorder. A post-hoc safety/tolerability analysis of data from the four acute trials in the cariprazine schizophrenia clinical development program (NCT00404573; NCT00694707; NCT01104766; NCT01104779) was carried out using the overall safety population (all patients who received >= 1 dose of study drug) and modal daily dose subgroups (1.5-3, 4.5-6, and 9-12 mg/day). These exploratory findings were summarized using descriptive statistics. Cariprazine was generally well tolerated. The incidence of treatmentemergent adverse events versus placebo was similar for cariprazine 1.5-3 mg/day and higher for cariprazine 4.5-6 and 9-12 mg/day; a dose-response relationship was observed for akathisia, extrapyramidal symptoms, and diastolic blood pressure. The mean changes in metabolic parameters were generally similar in cariprazine-treated and placebo-treated patients. There was no prolactin level increase or QTc value greater than 500 ms; small increases in mean body weight (similar to 1 to 2 kg) versus placebo were observed. Within the Food and Drug Administrationapproved dose range (1.5-6 mg/day), cariprazine was generally safe and well tolerated in patients with schizophrenia. Copyright (C) 2017 The Author(s). Published by Wolters Kluwer Health, Inc.