A Study of Brexpiprazole in Patients With Major Depressive Disorder

A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group-comparison Trial to Assess the Efficacy and Safety of Brexpiprazole as Adjunctive Therapy in Patients With Major Depressive Disorder

The purpose of this 14 week, randomized, double-blind, placebo controlled study is to assess the safety and efficacy of brexipiprazole to placebo as adjunctive treatment to an assigned open-label marketed antidepressant therapy (ADT) in patients with Major Depressive Disorder.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Brexpiprazole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 740
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukushima, Japan
    • Nanko-kokorono Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Outpatients, or inpatients at the time of informed consent whose treatment status can be successfully shifted to outpatient status before enrollment in the antidepressant treatment period
• Male and female patients ≥ 20 to < 65 years of age (at the time of informed consent)
• Patients who have a level of comprehension sufficient to allow them to give written informed consent to all of the observation/examination/evaluation items specified in the protocol, and who can understand the contents of the trial
• Patients with a DSM-5 classification-based diagnosis of "major depressive disorder, single episode" or "major depressive disorder, recurrent episode," and whose current episode has persisted for at least 8 weeks

Exclusion Criteria:

• Women who are pregnant or breastfeeding or who have positive pregnancy test (urine) results at screening
• Sexually active male subjects or sexually active female subjects of childbearing potential, who will not agree to practice 2 different methods of birth control or to remain abstinent during the trial and for 30 days after the final

IMP administration. For birth control, 2 of the following methods must be used:

vasectomy, tubal ligation, vaginal diaphragm, intra-uterine contraceptive device (IUD), oral contraceptives, or condom with spermicide.

• Patients with a treatment history showing that all antidepressants (including those not used for the current major depressive episode) cannot be tolerated
• Patients with a history of electroconvulsive therapy

• Patients with a diagnosis of any of the following diseases according to DSM-5

  1. Neurocognitive disorders
  2. Schizophrenia spectrum and other psychotic disorders
  3. Bipolar and related disorders
  4. Feeding and eating disorders
  5. Obsessive-compulsive disorder
  6. Panic disorder
  7. Posttraumatic stress disorder

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brexpiprazole 1mg; Tablets, Oral, 1mg once daily, 14 weeks Other Name: REXULTI	Drug: Brexpiprazole; Tablets, Oral, once daily, 14 weeks; Other Names: REXULTI
Experimental: Brexpiprazole 2mg; Tablets, Oral, 2 mg once daily, 14 weeks Other Name: REXULTI	Drug: Brexpiprazole; Tablets, Oral, once daily, 14 weeks; Other Names: REXULTI
Placebo Comparator: Placebo; Tablets, Oral, once daily, 14 weeks	Drug: Placebo; Tablets, Oral, once daily, 14 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Changes From Baseline (Week 8 of the Antidepressant Treatment Period [Phase A]) in the MADRS Total Scores at Week 6 of the Double-blind Period (Phase B).	The MADRS was a clinician-rated scale which evaluated the level of depression. The MADRS consisted of 10 items assessing apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thought. Each item was scored from 0 to 6, with higher scores indicating worse condition. Summed subscales were combined to compute a total score. Total score ranges from 0 to 60, with higher scores indicating worse condition.The mean changes were compared between antidepressant treatments and brexpiprazole as adjunctive therapy.	Baseline (the end of Phase A), at completion of administration (Week 6).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGI-I Improvement Rate at Week 6 of the Double-blind Period (Phase B)	Clinical Global Impression - Improvement (CGI-I) improvement rate: the proportion of participants who score 1 or 2 on the CGI-I scale at Week 6 of the double-blind period (Phase B). The CGI-I Scale was a clinician-rated scale which assessed the total improvement of the participant's condition compared to that at baseline. Scores range from 0 to 7:0 = Not assessed, 1= Very much improved, 2 = Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Higher scores indicated worse condition.	Baseline (the end of Phase A), at completion of administration (Week 6).

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Actual): June 6, 2022
• Study Completion (Actual): July 4, 2022

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: October 3, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; 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: 331-102-00058

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article Publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No