Otsuka Pharmaceutical Co., Ltd. Announces Results From A Phase 2 Study Of Investigational Product OPC-34712 As Adjunctive Therapy In Adults With MDD

Otsuka Pharmaceutical Co., Ltd. Announces Results From A Phase 2 Study Of Investigational Product OPC-34712 As Adjunctive Therapy In Adults With MDD

Otsuka Pharmaceutical Co., Ltd. (OPC) and Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) today announced results from a Phase 2 clinical touchstone of OPC-34712, a novel D2 dopamine limited agonist investigational product. In a six-week, double-incapable of judging, randomized, placebo-controlled study, OPC-34712 (1.5 ± 0.5 mg), while added to antidepressant therapy (ADT) in of mature age patients with major depressive disorder (MDD), who had exhibited every inadequate response to ADT, demonstrated melioration in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score (p=0.0303), the main endpoint of the study.

"These given conditions represent proof-of-concept that OPC-34712 may exist effective as adjunctive therapy in treating greater depressive disorder in patients with each inadequate response to ADT," said William H. Carson, M.D., President and CEO, OPDC. "Importantly, these facts allow us to advance to Phase 3 unfolding for OPC-34712 with confidence."

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

OPC-34712 is a fresh investigational psychotherapeutic compound developed to get ready improved efficacy and tolerability (e.g., in a ~ degree akathisia, restlessness and/or insomnia) very established adjunctive treatments for MDD. The compromise has broad activity across multiple monoamine systems and exhibits reduced indulgent agonist activity at D2 dopamine receptors and enhanced connection. for specific serotonin receptors (e.g., 5HT1a, 5HT2a and 5HT7). OPC-34712 is commonly poised to enter Phase 3 testing because schizophrenia and adjunctive treatment of MDD and is in Phase 2 testing in opposition to adjunctive treatment of adult ADHD.

Study Design and Findings

This Phase 2 multicenter, double-concealment, placebo-controlled study randomized 429 grown-up person MDD patients who exhibited an imperfect response to one to three ADTs in the current episode. The study was designed to assess the power and safety of OPC-34712 in the same manner with 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 phasis (7-28 days) that identified patients who had not responded to precedent ADT within the current depressive episode; II) a prospective 8-week, unbiassed-blind phase to assess response station to ADT; and III) a randomized appearance of 6-week, double-blind charge of adjunctive OPC-34712 compared to placebo in patients who had every inadequate response to ADT. Inadequate rejoinder to prospective ADT was defined similar to less than 50% decrease in Hamilton Depression Rating Score at the period of the 8-week single-hoodwink phase. Patients were randomized to quotidian OPC-34712 (0.15 mg, n=62; 0.50 ± 0.25 mg, n=120; or 1.5 ± 0.5 mg, n=121) or placebo (n=126) adjunctive to ADT.

The principal efficacy endpoint was mean change in the MADRS total score from baseline to Week 6 following randomization. Primary separation objectives were to compare the effectiveness of the 0.5 mg/~light dose and the 1.5 mg/generation dose of OPC-34712 with placebo. Improvements in measure MADRS total score, from baseline to endpoint since compared to placebo, were observed but for subjects receiving adjunctive OPC-34712 at the 1.5 mg/light of ~ dose compared with placebo (p=0.0303); improvements in MADRS sum ~ score for subjects receiving the 0.5 mg/~light dose were not different compared by placebo (p>0.05).

Overall achieving rates were 82-87% and like for all treatment groups. Discontinuations appropriate to adverse events ranged from 0.8% to 3.2% in whole treatment groups compared to 0.8% in the placebo study firth. The most common adverse events associated through OPC-34712 (all doses of OPC-34712 cumulatively greater than or measure to 5 percent vs. placebo) were upper respiratory tract infection (6.9% vs. 4.8%), akathisia (6.6% vs. 3.2%), pressure gain (6.3% vs. 0.8%), and nasopharyngitis (5.0% vs. 1.6%). Mean changes in body weight from baseline to last survey 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).

About Major Depressive Disorder

Major depressive jumble (MDD) is characterized by one or greater quantity major depressive episodes, (i.e., at smallest two weeks of depressed mood or ruin of interest accompanied by at smallest four additional symptoms of depression). MDD affects near 14.2 million American adults in a given year, and today it is ofttimes treated with antidepressants (1); however, in manifold cases patients fail to respond adequately to usage (2). Depression is one of the chief causes of disability in the U.S. In 2000, the whole economic burden of treating depression in the U.S. was $83.1 billion, through workplace costs, including missed days and destitution of productivity due to illness, accounting conducive to the majority of the total relating to housekeeping burden (62 percent). Other economic burdens in 2000 included $26.1 billion (31 percent) according to treatment costs and $5.4 billion (7 percent) on account of suicide-related costs (3).

1. Kessler, RC, Berglund, P, Demler, O, et al. The Epidemiology of Major Depressive Disorder Results From the National Comorbidity Survey Replication (NCS-R). JAMA. 2003; 289: 3095-3105.

2. Rush AJ, Trievdi NJ, Wisniewski SR, et al. Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report. Am J Psych. 2006; 163: 1905-1917.

3. Greenberg, P. Kessler, R. et al. The Economic Burden of Depression in the United States: How Did It Change Between 1990 and 2000? J Clin Psychiatry. 2003; 64: 1465-1475.