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

NCT02196506 | Completed Phase 3 Results

• 1 other identifier: 331-13-214
• Study Type: interventional
• Target: 837
• Locations: 5 countries
• Sites: 47

Brief Summary

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

Conditions

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders

Keywords

OPC-34712; brexpiprazole; Major Depressive Disorder; Adjunctive Treatment; Anxious Distress

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in the Sheehan Disability Scale (SDS) From Baseline to End of Treatment

  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

  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).

  From baseline (end of Phase A [Week 8]) to week 14

Study Arms (2)

Brexpiprazole + ADT

EXPERIMENTAL

Brexpiprazole + ADT

Drug: Brexpiprazole +ADT

Placebo + ADT

PLACEBO COMPARATOR

Placebo + ADT

Drug: Placebo + ADT

Interventions

Placebo + ADT DRUG

Placebo + ADT Placebo + FDA Approved Antidepressant (ADT)

Placebo + ADT

Brexpiprazole +ADT DRUG

Brexpiprazole + ADT Tablet, Oral, 2mg brexpiprazole and FDA Approved Antidepressant (ADT)

Brexpiprazole + ADT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• H. Lundbeck A/S: collaborator

Study Sites (47)

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Birmingham, Alabama, United States

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Beverly Hills, California, United States

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Denver, Colorado, United States

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Hialeah, Florida, United States

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Orlando, Florida, United States

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Alpharetta, Georgia, United States

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Smyrna, Georgia, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Rochester Hills, Michigan, United States

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Cherry Hill, New Jersey, United States

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Jamaica, New York, United States

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New York, New York, United States

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Staten Island, New York, United States

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Raleigh, North Carolina, United States

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Cincinnati, Ohio, United States

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Edmond, Oklahoma, United States

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Portland, Oregon, United States

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Salem, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Lincoln, Rhode Island, United States

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Columbia, South Carolina, United States

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Memphis, Tennessee, United States

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Wichita Falls, Texas, United States

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Murray, Utah, United States

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Woodstock, Vermont, United States

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Charlottesville, Virginia, United States

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Richmond, Virginia, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Achim, Germany

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Berlin, Germany

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Düsseldorf, Germany

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Frankfurt, Germany

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Freiburg im Breisgau, Germany

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Oranienburg, Germany

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Stralsund, Germany

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Würzburg, Germany

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Budapest, Hungary

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Győr, Hungary

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Gdansk, Poland

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Lubin, Poland

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Sosnowiec, Poland

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Warsaw, Poland

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Bratislava, Slovakia

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Kosice-Barca, Slovakia

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Liptovský Mikuláš, Slovakia

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Related Publications (9)

• Kapadia S, Zhang Z, Ardic F, Patel M, Thase ME, Papakostas GI. Adjunctive brexpiprazole in patients with major depressive disorder who show minimal or partial response to antidepressant treatment: post hoc analysis of randomized controlled trials. Int J Neuropsychopharmacol. 2025 Oct 1;28(10):pyaf074. doi: 10.1093/ijnp/pyaf074.

  PMID: 41055581 DERIVED

• Ardic F, Zhang Z, Hogan M. Effects of adjunctive brexpiprazole in patients with major depressive disorder and sleep disturbance: a post hoc analysis of three randomized trials. Front Psychiatry. 2025 Aug 7;16:1618176. doi: 10.3389/fpsyt.2025.1618176. eCollection 2025.

  PMID: 40852147 DERIVED

• Kapadia S, Zhang Z, Csoboth C, Patel M, Thase ME, Papakostas GI. Adjunctive brexpiprazole in patients with unresolved symptoms of depression on antidepressant treatment who are early in the disease course: post hoc analysis of randomized controlled trials. Int J Neuropsychopharmacol. 2025 Aug 1;28(8):pyaf050. doi: 10.1093/ijnp/pyaf050.

  PMID: 40607746 DERIVED

• McIntyre RS, Bubolic S, Zhang Z, MacKenzie EM, Therrien F, Miguelez M, Boucher M. Effects of Adjunctive Brexpiprazole on Individual Depressive Symptoms and Functioning in Patients With Major Depressive Disorder and Anxious Distress: Post Hoc Analysis of Three Placebo-Controlled Studies. J Clin Psychopharmacol. 2024 Mar-Apr 01;44(2):133-140. doi: 10.1097/JCP.0000000000001825.

  PMID: 38421922 DERIVED

• Newcomer JW, Meehan SR, Chen D, Brubaker M, Weiss C. Changes in Metabolic Parameters and Body Weight in Patients With Prediabetes Treated With Adjunctive Brexpiprazole for Major Depressive Disorder: Pooled Analysis of Short- and Long-Term Clinical Studies. J Clin Psychiatry. 2023 Aug 28;84(5):23m14786. doi: 10.4088/JCP.23m14786.

  PMID: 37656180 DERIVED

• McIntyre RS, Therrien F, Ismail Z, Meehan SR, Miguelez M, Larsen KG, Chen D, MacKenzie EM, Thase ME. Effects of adjunctive brexpiprazole on patient life engagement in major depressive disorder: Post hoc analysis of Inventory of Depressive Symptomatology Self-Report data. J Psychiatr Res. 2023 Jun;162:71-78. doi: 10.1016/j.jpsychires.2023.04.012. Epub 2023 Apr 12.

  PMID: 37099968 DERIVED

• 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.

  PMID: 31577867 DERIVED

• 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.

  PMID: 30508090 DERIVED

• 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.

  PMID: 29873953 DERIVED

MeSH Terms

Conditions

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders

Interventions

Androgen Antagonists

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Global Medical Affairs
• Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.

800 562-3974

Study Officials

• Claudette Brewer

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2014
• First Posted: July 22, 2014
• Study Start: July 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: May 1, 2016
• Last Updated: August 21, 2018
• Results First Posted: August 21, 2018

Record last verified: 2018-08

Locations

HU (2); PL (4); US (30); DE (8); SL (3)