Results for a phase 3 study of Cariprazine ( Vraylar ) for the treatment of adults with major depressive episodes associated with bipolar I disorder ( bipolar I depression ) were announced.
This is the second positive pivotal trial of Cariprazine for this investigational use.
In this study, the primary efficacy objective was met for both Cariprazine 1.5mg and 3mg dose groups ( p less than 0.05 ).
Both showed a significantly greater improvement than placebo for the change from baseline to week 6 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) total score.
In this study, Cariprazine was generally well tolerated. Sedation, somnolence, dizziness, akathisia and nausea were the most commonly reported adverse events ( reported with a frequency of 5% or greater and at least twice that of placebo ).
In this study, 5.0% of Cariprazine treated patients discontinued due to adverse events versus 2.5% of placebo treated patients.
RGH-MD-54 is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter, fixed-dose clinical trial in patients with bipolar I depression.
A total of 488 patients were randomized in this study aiming to evaluate the efficacy, safety, and tolerability of Cariprazine 1.5 mg/day and 3.0 mg/day compared to placebo in patients with bipolar I depression.
Subjects underwent a no-drug screening period of approximately 7-14 days, followed by 6 weeks of double-blind treatment and a 1-week, no investigational product safety follow-up period.
Cariprazine is an oral, once daily atypical antipsychotic approved for the acute treatment of adult patients with manic or mixed episodes associated with bipolar I disorder, with a recommended dose range of 3 to 6 mg/day, and for the treatment of schizophrenia in adults, with a recommended dose range of 1.5 to 6 mg/day.
While the mechanism of action of Cariprazine in schizophrenia and bipolar I disorder is unknown, the efficacy of Cariprazine could be mediated through a combination of partial agonist activity at central dopamine D₂ and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors.
Pharmacodynamic studies with Cariprazine have shown that it acts as a partial agonist with high binding affinity at dopamine D3, dopamine D2, and serotonin 5-HT1A receptors.
Cariprazine has demonstrated up to approximately 8-fold greater in vitro affinity for dopamine D3 vs D2 receptors.
Cariprazine also acts as an antagonist at serotonin 5-HT2B and 5-HT2A receptors with high and moderate binding affinity, respectively as well as it binds to the histamine H1 receptors.
Cariprazine shows lower binding affinity to the serotonin 5-HT2C and alpha1A- adrenergic receptors and has no appreciable affinity for cholinergic muscarinic receptors.
The clinical significance of these in vitro data is unknown. ( Xagena )
Source: Allergan, 2017