Date: 2014-12-10
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 53rd Annual Meeting of the American College of Neuropsychopharmacology (ACNP) December 7—11 2014, Phoenix, Arizona
Company: Lundbeck (Denmark) Otsuka Pharmaceutical (Japan)
Product: brexpiprazole (OPC-34712)
Action
mechanism: Brexpiprazole is a serotonin-dopamine activity modulator (SDAM) that acts as a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all with similar high potency (< 1nM).
Brexpiprazole is a novel investigational psychotropic compound discovered by Otsuka and under co-development with Lundbeck. A New Drug Application for brexpiprazole has been filed with the US FDA and the PDUFA date is in July 2015.
Disease: patients with major depressive disorder (MDD) who had an inadequate response to monotherapy antidepressant treatments (ADT)
Therapeutic area: CNS diseases - Mental diseases
Country:
Trial details:
Latest
news: * On December 10, 2014, Otsuka Pharmaceutical and Lundbeck announced the presentation of Phase III study results evaluating the efficacy of investigational compound brexpiprazole as adjunctive treatment to antidepressant therapy (ADT) in patients with major depressive disorder (MDD) at the 53rd Annual Meeting of the American College of Neuropsychopharmacology (ACNP) in Phoenix, Arizona. The data were shared in a poster presentation, \"Efficacy and Safety of Adjunctive Brexpiprazole (OPC-34712) in Major Depressive Disorder: Results of Two Pivotal Clinical Studies.\" The poster featured results of two Phase III clinical studies evaluating the efficacy, safety and tolerability of adjunctive brexpiprazole in patients with MDD and inadequate response to ADT (Study 1: NCT01360645; Study 2: NCT01360632). Patients with MDD who failed to reach adequate response during 1-3 treatment attempts with ADT (which is commonly found in current clinical practice) were enrolled and received an additional trial with a (single-blind) ADT for 8 weeks. Those patients who still failed to reach an adequate response throughout this phase were then randomized (double-blind) to ADT and brexpiprazole or ADT and placebo for 6 weeks. The primary endpoint for both studies was change in MADRS (Montgomery—Åsberg Depression Rating Scale) Total Score from baseline to Week 6. Pre-specified analyses were conducted both on the efficacy population and on the final protocol population (fulfilling amended randomization criteria) for each individual study. In both studies, key findings included:
· Adjunctive brexpiprazole showed greater improvement than adjunctive placebo in MADRS total score at Week 6 in the efficacy population per final protocol in Study 1 (2mg+ADT [N=175]: -3.21, p=0.0002), and in Study 2 (1mg+ADT [N=211]: -1.30, p=0.0737; 3mg+ADT [N=213]: -1.95, p=0.0079). Similar results were observed for the efficacy population in both studies.
· The completion rate was high (>90%) and comparable across brexpiprazole and placebo groups. Discontinuations due to adverse events were low across all groups (1mg = 1.3%, 2mg = 3.2%, 3mg = 3.5%, placebo = 0.7%) and only one patient discontinued due to lack of efficacy (in the brexpiprazole 1mg group).
· All doses of adjunctive brexpiprazole resulted in notably low levels of sedating or activating side effects.
· The most frequent adverse events (incidence >5% in any group and more than twice the incidence in the placebo group across the two studies) included akathisia (4.4%, 7.4%, 13.5% vs.1.7%), weight increase (6.6%, 8.0%, 5.7% vs. 1.9%), tremor (4.0%, 2.1%, 5.2% vs. 2.2%) somnolence (4.0%, 4.3%, 5.7% vs. 0.5%) and nasopharyngitis (6.6%, 1.1%. 3.1% vs. 1.7%), in the brexpiprazole 1mg+ADT (N=226), 2mg+ADT (N=188), 3mg+ADT (N=229) versus combined placebo + ADT groups (N=411), respectively.
The results from Study 1 were previously presented in a poster session at the 22nd European Psychiatry Association Congress (EPA) in March 2014.
