Study of the Safety and Efficacy of Fixed-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder With and Without Anxious Distress

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of the Safety and Efficacy of Fixed-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder With and Without Anxious Distress

The purpose of this study is to assess the tolerability, safety, and efficacy of brexpiprazole (2.0 mg/day) as adjunctive therapy in adult subjects with a diagnosis of MDD with and without anxious distress

Study Overview

• Status: Completed
• Conditions: Mental Disorders; Depressive Disorder; Depression; Mood Disorders; Depressive Disorder, Major
• Intervention / Treatment: Drug: Brexpiprazole +ADT; Drug: Placebo + ADT

Detailed Description

The introduction of atypical antipsychotics has created a renewed interest in adjunctive therapy for MDD, particularly for treatment-resistant MDD. Several atypical antipsychotics have been shown to enhance the response to ADT. This is a phase 3, multicenter, randomized, double-blind, placebo-controlled, fixed-dose trial designed to assess the safety and efficacy of brexpiprazole (2.0 mg/day) as adjunctive therapy to an assigned open-label ADT in depressed subjects with and without anxious distress.

• Study Type: Interventional
• Enrollment (Actual): 837
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Achim, Germany
  • Berlin, Germany
  • Dusseldorf, Germany
  • Frankfurt, Germany
  • Freiburg, Germany
  • Oranienburg, Germany
  • Stralsund, Germany
  • Wurzburg, Germany
• Hungary
  • Budapest, Hungary
  • Gyor, Hungary
• Poland
  • Gdansk, Poland
  • Lubin, Poland
  • Sosnowiec, Poland
  • Warszawa, Poland
• Slovakia
  • Bratislava, Slovakia
  • Kosice-Barca, Slovakia
  • Liptovsky Mikulas, Slovakia
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • California
    • Beverly Hills, California, United States
  • Colorado
    • Denver, Colorado, United States
  • Florida
    • Hialeah, Florida, United States
    • Orlando, Florida, United States
  • Georgia
    • Alpharetta, Georgia, United States
    • Smyrna, Georgia, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • Rochester Hills, Michigan, United States
  • New Jersey
    • Cherry Hill, New Jersey, United States
  • New York
    • Jamaica, New York, United States
    • New York, New York, United States
    • Staten Island, New York, United States
  • North Carolina
    • Raleigh, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Oklahoma
    • Edmond, Oklahoma, United States
  • Oregon
    • Portland, Oregon, United States
    • Salem, Oregon, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
  • Rhode Island
    • Lincoln, Rhode Island, United States
  • South Carolina
    • Columbia, South Carolina, United States
  • Tennessee
    • Memphis, Tennessee, United States
  • Texas
    • Wichita Falls, Texas, United States
  • Utah
    • Murray, Utah, United States
  • Vermont
    • Woodstock, Vermont, United States
  • Virginia
    • Charlottesville, Virginia, United States
    • Richmond, Virginia, United States
  • Washington
    • Seattle, Washington, United States
    • Spokane, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and Female subjects between 18-65 years of age, with diagnosis of major depressive disorder with or without anxious distress
• Current depressive episode must be at least 8 weeks in duration

Exclusion Criteria:

• Subjects with a history of Neuroleptic Malignant Syndrome or Serotonin Syndrome
• Subjects who report an inadequate response to more than 3 antidepressant treatments in the current episode
• Subjects with a current Axis I diagnosis of: Delirium, dementia, amnestic or other cognitive disorder, Schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I or II disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brexpiprazole + ADT	Drug: Brexpiprazole +ADT; Brexpiprazole + ADT Tablet, Oral, 2mg brexpiprazole and FDA Approved Antidepressant (ADT)
Placebo Comparator: Placebo + ADT	Drug: Placebo + ADT; Placebo + ADT Placebo + FDA Approved Antidepressant (ADT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Montgomery-Asberg Depression	To assess the change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score from Baseline (End of Phase A [Week 8]) to Week 14. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The rater decided whether the rating lied on predefined scale steps (0, 2, 4, 6) or between them (1, 3, 5). The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected.	From baseline (end of Phase A [Week 8]) to week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Sheehan Disability Scale (SDS) From Baseline to End of Treatment	To assess the change in the Sheehan Disability Scale (SDS) Score (the mean of 3 individual item scores) from Baseline (End of Phase A [Week 8]) to Week 14 (End of Phase B). SDS was a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life, and family life/home responsibility. Each item was scored using a scale of 0 to 10 (a higher score indicates symptoms have disrupted work, social life, and family life/home responsibility extremely). The maximum total score was 30; 0 = not at all, to 30 = extremely.	From baseline (end of Phase A [Week 8]) to week 14
Change From End of Phase A to End of Phase B in MADRS Total Score for the Subpopulation With <25% Improvement From Baseline of Phase A to End of Phase A in MADRS Total Score	To assess the change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in MADRS Total Score for the subpopulation with < 25% improvement from baseline of Phase A (Week 0) to end of Phase A (Week 8) in MADRS Total Score. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected.	From baseline (end of Phase A [Week 8]) to week 14
Change From End of Phase A to End of Phase B in MADRS Total Score for the Subpopulations With Anxious Distress as Specified in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).	To assess the change from end of Phase A (Week 8) to end of Phase B (Week 14) in MADRS Total Score for the subpopulations with anxious distress as specified in DSM-V. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected.	From baseline (end of Phase A [Week 8]) to week 14

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: H. Lundbeck A/S
• Investigators: Study Director: Claudette Brewer, Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

General Publications

• Newcomer JW, Eriksson H, Zhang P, Meehan SR, Weiss C. Changes in Metabolic Parameters and Body Weight in Patients With Major Depressive Disorder Treated With Adjunctive Brexpiprazole: Pooled Analysis of Phase 3 Clinical Studies. J Clin Psychiatry. 2019 Oct 1;80(6):18m12680. doi: 10.4088/JCP.18m12680.
• Hobart M, Zhang P, Weiss C, Meehan SR, Eriksson H. Adjunctive Brexpiprazole and Functioning in Major Depressive Disorder: A Pooled Analysis of Six Randomized Studies Using the Sheehan Disability Scale. Int J Neuropsychopharmacol. 2019 Mar 1;22(3):173-179. doi: 10.1093/ijnp/pyy095.
• Hobart M, Skuban A, Zhang P, Augustine C, Brewer C, Hefting N, Sanchez R, McQuade RD. A Randomized, Placebo-Controlled Study of the Efficacy and Safety of Fixed-Dose Brexpiprazole 2 mg/d as Adjunctive Treatment of Adults With Major Depressive Disorder. J Clin Psychiatry. 2018 May 22;79(4):17m12058. doi: 10.4088/JCP.17m12058.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: July 18, 2014
• First Submitted That Met QC Criteria: July 18, 2014
• First Posted (Estimate): July 22, 2014

Study Record Updates

• Last Update Posted (Actual): August 21, 2018
• Last Update Submitted That Met QC Criteria: August 17, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; OPC-34712; brexpiprazole; Adjunctive Treatment; Anxious Distress
• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Depression; Depressive Disorder; Disease; Mental Disorders; Mood Disorders; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Dopamine Agonists; Dopamine Agents; Brexpiprazole
• Other Study ID Numbers: 331-13-214