A pooled post hoc analysis evaluating the safety and tolerability of cariprazine in bipolar depression.

Abstract

BACKGROUND\nThe safety and efficacy of cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, was evaluated in 4 randomized, double-blind, placebo-controlled trials in patients with bipolar depression.\n\n\nMETHODS\nSafety and tolerability were evaluated in 2 post hoc analyses. Modal dose analysis: pooled data from all 4 flexible/fixed-dose trials (dose groups: <1.5, 1.5, 3\xa0mg/d). Fixed-dose analysis: pooled data from 2 identically designed fixed-dose trials (1.5 and 3\xa0mg/d dose groups).\n\n\nRESULTS\nThe modal dose and fixed-dose analyses evaluated data from 1775 and 970 patients, respectively. Cariprazine was generally safe and well tolerated; study completion rates were 78% and 82% in the modal dose and fixed-dose analyses, respectively. In modal dose analysis, treatment-emergent adverse events (TEAEs) occurred in 60% of overall cariprazine- and 55% of placebo-treated patients; nausea (8% vs 3%) and akathisia (7% vs 2%) occurred in ≥5% of cariprazine patients and twice the rate of placebo. Metabolic changes were small and generally similar for cariprazine and placebo; mean increase in glucose was 3.1\xa0mg/dL for cariprazine and 2.6\xa0mg/dL for placebo. Fixed-dose and modal dose findings were generally consistent; values for most metabolic parameters were slightly higher for fixed-dose 3\xa0mg/d versus 1.5\xa0mg/d.\n\n\nLIMITATIONS\nPost hoc analyses, modal dose groups, short treatment duration.\n\n\nCONCLUSIONS\nIn modal dose (0.25-3\xa0mg/d) and fixed-dose (1.5 and 3\xa0mg/d) analyses, cariprazine was generally safe and well tolerated in the treatment of bipolar depression. Slightly improved tolerability was observed with fixed-dose cariprazine 1.5\xa0mg/d versus 3\xa0mg/d.\n\n\nTRIAL REGISTRATION\nclinicaltrials.gov NCT00852202, NCT01396447, NCT02670538, NCT02670551.