Otsuka Pharmaceutical reports OPC-34712 Phase 2 trial results in major depressive disorder

May 16 2011

Otsuka Pharmaceutical Co., Ltd. (OPC) and Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) today announced results from a Phase 2 clinical trial of OPC-34712, a novel D₂ dopamine partial agonist investigational product. In a six-week, double-blind, randomized, placebo-controlled study, OPC-34712 (1.5 ± 0.5 mg), when added to antidepressant therapy (ADT) in adult patients with major depressive disorder (MDD), who had exhibited an inadequate response to ADT, demonstrated improvement in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score.

"These data represent proof-of-concept that OPC-34712 may be effective as adjunctive therapy in treating major depressive disorder in patients with an inadequate response to ADT," said William H. Carson, M.D., President and CEO, OPDC. "Importantly, these data allow us to advance to Phase 3 development for OPC-34712 with confidence."

Trial results were presented at the American Psychiatric Association's 2011 annual meeting. "Because many patients who suffer from major depressive disorder do not respond adequately to existing therapies, it's critical that we continue to investigate new compounds as adjunctive therapy," said Study Investigator Michael E. Thase, M.D., Professor of Psychiatry, University of Pennsylvania School of Medicine. "The findings from this study advance our knowledge about the utility of adjunctive agents in patients who do not optimally respond to antidepressants alone."

OPC-34712 is a novel investigational psychotherapeutic compound developed to provide improved efficacy and tolerability (e.g., less akathisia, restlessness and/or insomnia) over established adjunctive treatments for MDD. The compound has broad activity across multiple monoamine systems and exhibits reduced partial agonist activity at D₂ dopamine receptors and enhanced affinity for specific serotonin receptors (e.g., 5HT_1a, 5HT_2a and 5HT₇). OPC-34712 is currently poised to enter Phase 3 testing for schizophrenia and adjunctive treatment of MDD and is in Phase 2 testing for adjunctive treatment of adult ADHD.

Study Design and Findings

This Phase 2 multicenter, double-blind, placebo-controlled study randomized 429 adult MDD patients who exhibited an inadequate response to one to three ADTs in the current episode. The study was designed to assess the efficacy and safety of OPC-34712 as an adjunctive treatment to standard ADT. The ADTs included in the study were desvenlafaxine, escitalopram, fluoxetine, paroxetine, sertraline, and venlafaxine.

The study was comprised of three phases: I) a screening phase (7-28 days) that identified patients who had not responded to prior ADT within the current depressive episode; II) a prospective 8-week, single-blind phase to assess response status to ADT; and III) a randomized phase of 6-week, double-blind assessment of adjunctive OPC-34712 compared to placebo in patients who had an inadequate response to ADT. Inadequate response to prospective ADT was defined as less than 50% decrease in Hamilton Depression Rating Score at the end of the 8-week single-blind phase. Patients were randomized to daily OPC-34712 (0.15 mg)

The primary efficacy endpoint was mean change in the MADRS total score from baseline to Week 6 following randomization. Primary analysis objectives were to compare the efficacy of the 0.5 mg/day dose and the 1.5 mg/day dose of OPC-34712 with placebo. Improvements in mean MADRS total score, from baseline to endpoint as compared to placebo, were observed only for subjects receiving adjunctive OPC-34712 at the 1.5 mg/day dose compared with placebo.

Overall completion rates were 82-87% and similar for all treatment groups. Discontinuations due to adverse events ranged from 0.8% to 3.2% in all treatment groups compared to 0.8% in the placebo study arm. The most common adverse events associated with OPC-34712 (all doses of OPC-34712 cumulatively greater than or equal to 5 percent vs. placebo) were upper respiratory tract infection (6.9% vs. 4.8%), akathisia (6.6% vs. 3.2%), weight gain (6.3% vs. 0.8%), and nasopharyngitis (5.0% vs. 1.6%). Mean changes in body weight from baseline to last visit were: placebo = 0.77 kg, 0.15 mg OPC-34712 = 0.91 kg (p>0.05), 0.5 mg OPC-34712 = 1.33 kg (p<0.05) and 1.5 mg OPC 34712 = 1.66 kg (p<0.05).