Forest Laboratories And Gedeon Richter Plc Announce Results From A Phase II Study Of Cariprazine As Adjunctive Therapy In Major Depressive Disorder

Forest Laboratories, Inc. (NYSE: FRX) and Gedeon Richter Plc. announced preliminary top-line results from an 8-week Phase II clinical trial of the novel, investigational antipsychotic agent cariprazine as adjunctive therapy in major depressive disorder. Cariprazine is currently undergoing Phase III trials for the separate and additional indications of schizophrenia and bipolar mania.


In this exploratory Phase II trial, a total of 231 patients were randomized to enter one of two active (low dose or high dose) treatment arms or placebo. The primary endpoint was the Montgomery Asberg Depression Rating Scale (MADRS) score. Although the overall difference observed between the drug-treated and placebo-treated groups was not statistically significant, over the course of the trial, there was evidence of a treatment effect in the high-dose arm of the study compared to placebo.


In addition, tolerability results for cariprazine support further investigation in this patient population. Approximately 3% of patients discontinued the study early due to adverse events in the high-dose and 1% in the low-dose study arm compared to 3% in the placebo arm.


The companies are considering conducting an additional Phase II dose-response trial examining a wider range of doses.


About the Study


This Phase II trial was a U.S. multicenter, randomized double-blind, placebo-controlled, parallel, flexible-dose group study that evaluated the efficacy, safety and tolerability of once-daily cariprazine in patients with major depressive disorder who failed to respond to at least 2 antidepressant therapies (ADT). Following a washout period of no drug therapy for one week and 8 weeks of prospective ADTs, a total of 231 patients, between ages 18 and 65 years old, were randomized to one of three treatment arms (either 0.1-0.3 mg per day cariprazine + ADT, 1.0-2.0 mg per day cariprazine + ADT, or placebo + ADT). The primary endpoint was defined as change from randomization baseline to end of Week 8 in the MADRS total score.


About Cariprazine


Cariprazine, discovered by researchers at Gedeon Richter, is an orally active, potent D3/D2 partial agonist that preferentially binds to D3 receptors. Cariprazine also has a relatively low potency at other receptor sites, such as 5-HT2C, histamine H1, and muscarinic and adrenergic receptor sites which have been associated with adverse events. Cariprazine demonstrated a reduction in symptoms in previously reported Phase II clinical trials for schizophrenia and bipolar mania.