A Long-Term Study of Brexpiprazole in Patients With Major Depressive Disorder

A Multi-center, Open-label Trial to Assess the Long-term Safety and Efficacy of Brexpiprazole as Adjunctive Therapy in Patients With Major Depressive Disorder

This trial is a 52-week study to assess the safety of long-term use of brexpiprazole as adjunctive therapy in combination with an antidepressant.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Shirakawa, Japan
    • Nanko-kokorono clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Rollover subjects

  1. Outpatients
  2. Subjects who have completed the double-blind period of the double-blind trial and can commence the treatment period of this trial within 28 days from the completionof the double-blind period of the double-blind trial
  3. Subjects 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
  4. Subjects with a DSM-5 classification-based diagnosis of "major depressive disorder, single episode" or "major depressive disorder, recurrent episode"

• New subjects

  1. Outpatients
  2. Male and female patients ≥ 65 years of age (at the time of informed consent)
  3. Subjects 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
  4. Patients with a DSM-5 classification-based diagnosis of "major depressive disorder, single episode" or "major depressive disorder, recurrent episode" whose current episode has persisted for at least 8 weeks

Exclusion Criteria:

• Rollover subjects

  1. Female subjects who are pregnant or breastfeeding or who have positive pregnancy test (urine) results at baseline
  2. 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.
  3. Subjects who experience a change to the manic state in the antidepressant treatment period of the double-blind trial
  4. Subjects who are discovered to not meet the inclusion criteria or to fall under any of the exclusion criteria in the doubleblind trial
  5. Subjects who showed marked noncompliance with the IMP treatment in the double-blind trial (subjects whose IMP compliance rates are < 65% between prescribed visits)

• New subjects

  1. Sexually active male subjects who will not agree to practice 2different 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.
  2. Patients with a treatment history showing that all antidepressants (also including those not used for the current major depressive episode) cannot be tolerated
  3. Patients with a history of electroconvulsive therapy

  4. 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: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Brexpiprazole; 2 mg/day (starting dose 1mg/day) of Brexpiprazole will be orally administered once daily	Drug: Brexpiprazole; 2 mg/day (starting dose 1mg/day) of Brexpiprazole will be orally administered once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The frequency of Adverse Events	The incidence of the following events will be summarized: •Adverse events occurring after initiation of Interventional Medicinal Product administration	From baseline to week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean changes from baseline in Montgomery Åsberg Depression Rating Scale（MADRS) at Week 52.	The proportion of subjects who decrease MADRS total scores more than 50%. Reaction Rate and Remission Rate.The MADRS consists 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 is scored from 0 to 6, with higher scores indicating worse condition.	Baseline and Week 52
The proportion of subjects who score 1 or 2 on the Clinical Global Impression-Improvement(CGI-I) scale at Week 52	The CGI-I Scale is a clinician-rated scale which assesses the total improvement of the patient'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 indicate worse condition.	Baseline and Week 52
Mean changes from baseline in Clinical Global Impression-Severity of illness(CGI-S) at Week 52	The CGI-S Scale is a clinician-rated scale which assesses how mentally ill the patient is at the time. Scores range from 0 to 7: 0 = Not assessed, 1= Normal, not at all ill, 2 =Borderline mentally ill, 3= Mildly ill, 4= Moderately ill, 5= Markedly ill, 6= Severely ill, 7= Among the most extremely ill patients. Higher scores indicate worse condition.	Baseline and Week 52
Mean changes from baseline in Hamiliton Depression Rating Scale(HAM-D) item total scores at Week 52	The HAM-D is a clinician-rated scale which evaluates the level of depression. The HAM-D consists of 17 items such as depression mood, feeling of guilt, suicide, insomnia, work and activities, retardation, and so on. Each item is scored from 0 to 2, 3 or 4, with higher scores indicating worse condition. Summed subscales are combined to compute a total score. Total score ranges from 0 to 53 , with higher score indicating worse condition.	Baseline and Week 52
Mean changes from baseline in Sheehan Disability Scale (SDS) scores at Week 52	SDS Scale is a patient-rated scale which assesses the degree of impairment for each of 3 items ("work/school," "social life," and "family life/home responsibilities") on a 11-point scale ranging from 0 to 10 and the number of "days lost" and "days unproductive" caused by in the past week.	Baseline and Week 52

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 4, 2018
• Primary Completion (ACTUAL): March 17, 2021
• Study Completion (ACTUAL): April 13, 2021

Study Registration Dates

• First Submitted: July 29, 2018
• First Submitted That Met QC Criteria: November 7, 2018
• First Posted (ACTUAL): November 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 1, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

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: 331-102-00059

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