A Trial to Evaluate the Efficacy, Safety & Tolerability of Brexpiprazole in the Maintenance Treatment of Adults With Major Depressive Disorder

NCT03538691 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 331-201-000792018-000601-22
• Study Type: interventional
• Target: 1,149
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder (MDD) is a serious medical illness associated with significant suicidal risk and marked disability. Despite the availability of numerous treatments, achievement of consistent and favorable long-term outcomes remains challenging. This study will assess the safety, efficacy and tolerability of brexpiprazole as adjunctive therapy to protocol-specific open-label antidepressant therapy.

Conditions

Major Depressive Disorder

Keywords

Brexpiprazole; MDD

Outcome Measures

Primary Outcomes (1)

• Phase C: Time-to-Relapse by Any Criteria as Defined in Blinded Addendum

  Relapse criteria included:At same visit, increase in Montgomery Asberg Depression Rating Scale\[MADRS\] total score(10 items, 0=no symptoms to 6=severe symptoms,total score=0 to 60)of 50% from randomization and Clinical Global Impression-Severity of Illness \[CGI-\](8-point scale of 0=not assessed to 7=most extremely ill)score ≥4,hospitalization for depression, discontinuation for lack of efficacy/worsening of depression, active suicidality(score of ≥4 on MADRS item10 of suicidality)or yes answered on question 4 or 5 of Columbia-Suicide Severity Rating Scale\[C-SSRS\](Suicidal Ideation \[SI\] has 5 questions: wish to be dead,non-specific active suicidal thoughts,active SI with any methods \[not plan\]without intent to act,active SI with some intent to act without specific plan,active SI with specific plan,intent)or yes answered to any question in suicidal behavior section (5 questions:preparatory acts/behavior,aborted attempt,interrupted attempt,actual attempt\[non-fatal\],completed suicide).

  Up to 14 days post last dose in Phase C (up to 28 weeks)

Secondary Outcomes (7)

• Phase C: Change From Baseline for Randomization Phase in Sheehan Disability Scale (SDS) Mean Total Score at Week 46

  Baseline and Week 46

• Phase C: Time-to-functional Relapse Based on SDS Criteria

  Up to 14 days post last dose in Phase C (up to 28 weeks)

• Phase C: Percentage of Participants Meeting Any Relapse Criteria

  Up to 26 weeks in Phase C

• Phase C: Percentage of Participants Maintaining Remission

  Weeks 21, 23, 25, 29, 33, 37, 41, 45, and 46

• Phase C: Change From Baseline for Randomization Phase in MADRS Total Score at Week 46

  Baseline and Week 46

Study Arms (4)

Phase A: Brexpiprazole + ADT

EXPERIMENTAL

Participants received brexpiprazole 2 or 3 milligrams per day (mg/day) along with protocol-specified antidepressant therapy (ADT), orally, for 6 to 8 weeks during Phase A. Participants were initially titrated to a target dose of brexpiprazole 2 mg over a 2 to 4-week period. Thereafter, participants who had not met response criteria as defined in the blinded addendum, did not have potentially dose-related adverse events (AEs), and had not achieved the maximum dose of medication had their dose increased up to 3 mg.

Drug: Brexpiprazole; Drug: Antidepressant therapy

Phase B: Brexpiprazole + ADT

EXPERIMENTAL

Eligible participants completing Phase A were enrolled in Phase B to receive brexpiprazole 2 or 3 mg/day along with protocol-specified ADT, orally, for 12 weeks.

Drug: Brexpiprazole; Drug: Antidepressant therapy

Phase C: Brexpiprazole + ADT

EXPERIMENTAL

Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.

Drug: Brexpiprazole; Drug: Antidepressant therapy

Phase C: Placebo + ADT

EXPERIMENTAL

Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.

Drug: Antidepressant therapy

Interventions

Brexpiprazole DRUG

Administered as tablets.

Also known as: OPC-34712, Rexulti

Phase A: Brexpiprazole + ADT; Phase B: Brexpiprazole + ADT; Phase C: Brexpiprazole + ADT

Antidepressant therapy DRUG

Protocol-specified oral ADTs included: citalopram hydrobromide (Celexa®) tablets, escitalopram (Lexapro®) tablets, fluoxetine (Prozac®) capsules, paroxetine (Paxil CR®) controlled-release tablets, sertraline (Zoloft®) tablets, duloxetine (Cymbalta®) delayed-release capsules, venlafaxine XR (Effexor XR®) extended-release (XR) capsules.

Phase A: Brexpiprazole + ADT; Phase B: Brexpiprazole + ADT; Phase C: Brexpiprazole + ADT; Phase C: Placebo + 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:

• Participants with both a diagnosis of recurrent major depressive disorder, and in a current major depressive episode of ≥ 8 weeks in duration, as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and confirmed by both the Mini International Neuropsychiatric Interview (MINI) and an adequate clinical psychiatric evaluation.
• Participants must have reported a history for the current major depressive episode of an inadequate response to 1 or 2 adequate antidepressant treatments, and participants must currently be taking a protocol-mandated antidepressant treatment at an adequate dose and duration, and most not have reported ≥ 50% improvement. For participants who are currently on an adequate dose of protocol-mandated antidepressant therapy (ADT), but for an inadequate duration, can use the screening period to achieve adequate duration. At Phase A baseline visit, all participants must have either 2 or 3 documented inadequate responses to antidepressant treatment in total for the current episode as defined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ).
• Participants with a Hamilton Rating Scale for Depression (HAM-D17) total score ≥ 18 at the screening visit, and Phase A baseline visits.
• Participants willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period.

You may not qualify if:

• Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving investigational medicinal product (IMP).
• Sexually active males or females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of IMP.
• Participants who report treatment with adjunctive antipsychotic medication with an antidepressant for a minimum of 3 weeks during the current major depressive episode.
• Participants who report allergies or an intolerability (lifetime treatment history) to trial-provided ADTs that have not been prescribed to the participant during the current major depressive episode.
• Participants who have received electroconvulsive therapy (ECT) for the current major depressive episode.
• Participants who have had an inadequate response to ECT at any time in the past or who have had a vagus nerve stimulation or deep brain stimulation device implanted at any time for the management of treatment-resistant depression. Participants who have had transcranial magnetic stimulation during the current major depressive episode.
• Participants with a current need for involuntary commitment or who have been hospitalized within 4 weeks of screening for the current major depressive episode.
• Participants with a primary DSM-5 diagnosis of:
• Schizophrenia Spectrum and Other Psychotic Disorders
• Bipolar and Related Disorders
• Obsessive Compulsive Disorders
• Feeding and Eating Disorders
• Neurocognitive Disorders
• Panic Disorder
• Post-Traumatic Stress Disorder

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (1)

For additional information regarding sites, contact 844-687-8522

Los Angeles, California, 90024, United States

Location

Related Publications (1)

• McIntyre RS, Sundararajan K, Behl S, Hefting N, Jin N, Brewer C, Hobart M, Thase ME. A double-blind, placebo-controlled, randomised withdrawal study of adjunctive brexpiprazole maintenance treatment for major depressive disorder. Acta Neuropsychiatr. 2024 Oct 17;37:e33. doi: 10.1017/neu.2024.32.

  PMID: 39415650 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

brexpiprazole

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Otsuka Pharmaceutical Co., LTD.

CL_OPCJ_RDA_Team@otsuka.jp

+81-3-6361-7366

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: May 29, 2018
• Study Start: July 13, 2018
• Primary Completion: July 8, 2022
• Study Completion: July 29, 2022
• Last Updated: October 12, 2023
• Results First Posted: October 12, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Locations

US (1)