Major Depressive DisorderPhase 3NCT03538691
A Trial to Evaluate the Efficacy, Safety & Tolerability of Brexpiprazole in the Maintenance Treatment of Adults With Major Depressive Disorder
A Phase 3 study testing Brexpiprazole and Antidepressant therapy in people with Major Depressive Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Brexpiprazole and Antidepressant therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,149 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jul 2018to 29 Jul 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 36Show fewer
- 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
- Participants with a current DSM-5 diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder or intellectual disability.
- Participants experiencing hallucinations, delusions, or any psychotic symptomatology in the current major depressive episode.
- Participants receiving new onset psychotherapy (individual, group, marriage or family therapy) within 42 days of screening or at any time during participation in the trial.
- Participants who have met DSM-5 criteria for substance use disorder (moderate or severe) within the past 60 days; including alcohol and benzodiazepines, but excluding nicotine.
- Participants with hypothyroidism or hyperthyroidism (unless condition has been stabilized with medications for at least the past 90 days) and/or an abnormal result for free T4 at screening.
- Participants who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders such as any history of myocardial infarction, congestive heart failure, HIV seropositive status/acquired immunodeficiency syndrome, chronic hepatitis B or C.
- Participants with diabetes mellitus (IDDM and non-IDDM) are ineligible for the trial unless their condition is stable and well-controlled.
- Participants with uncontrolled hypertension (DBP > 95 millimetres of mercury [mmHg]) or symptomatic hypotension, or orthostatic hypotension which is defined as a decrease of ≥ 30 mmHg in systolic blood pressure (SBP) and/or decrease of ≥ 20 mmHg in diastolic blood pressure (DBP) after at least 3 minutes standing compared to the previous supine blood pressure OR development of symptoms.
- Participants with known ischemic heart disease or history of myocardial infarction-or congestive heart failure (whether controlled or uncontrolled).
- Participants with epilepsy or a history of seizures, except for a single seizure episode.
- Participants with a positive drug screen for cocaine or other drugs of abuse (excluding known prescription stimulants and other medications and marijuana). Detectable levels of alcohol, marijuana, barbiturates, or opiates in the drug screen are not exclusionary if, in the investigator's documented opinion, the participant does not meet DSM-5 criteria for moderate to severe substance use disorder and the positive test does not signal a clinical condition that would impact the safety of the participant or interpretation of the trial results, and participation is agreed to by the medical monitor prior to treatment.
- Treatment with a monoamine oxidase inhibitor (MAOI) within 14 day prior to the first dose of IMP in Phase A.
- Use of benzodiazepines and/or hypnotics (including non-benzodiazepine sleep aids) within 7 days prior to first dose of IMP in Phase A.
- Use of varenicline within 5 days prior to the first dose of IMP in Phase A.
- Use of oral (or immediate release intramuscular) neuroleptics within 7 days prior or long-acting approved neuroleptics ≤ 1 full cycle plus 1/2 cycle prior to the first dose of IMP in Phase A.
- Participants who would be likely to require prohibited concomitant therapy during the trial.
- Participants who have been exposed to brexpiprazole in any prior clinical trial or has received commercial brexpiprazole (Rexulti).
- Participants with a history of neuroleptic malignant syndrome or serotonin syndrome.
- Participants with a history of true allergic response to more than one class of medications.
- Prisoners or participants who are compulsorily detained for treatment of either a psychiatric or physical illness.
- Participants who participated in any clinical trial within the last 60 days or who participated in more than 2 clinical trials within the past year.
Trial locations and contacts
1 site in 1 country.
United States1 site
For additional information regarding sites, contact 844-687-8522
Los Angeles, California, 90024
About this study
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole as Adjunctive Therapy in the Maintenance Treatment of Adults With Major Depressive Disorder
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
- Being tested
- Brexpiprazole, Antidepressant therapy
- Keywords
- Brexpiprazole, MDD
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrexpiprazoleDrug
Also called OPC-34712, Rexulti
Administered as tablets.
Antidepressant therapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Antidepressant therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0=not at all, to 10=extremely. The SDS total score is the mean of the 3 item responses. The SDS total score ranges from 0 to 10, with higher scores indicating greater functional impairment. Baseline was defined as the last available assessment value between Week 14 and Week 20 in Phase B for this outcome measure. Analysis of covariance (ANCOVA) model was used for analysis.
Measured: Baseline and Week 46
Phase C: Time-to-functional Relapse Based on SDS Criteria
Time-to-functional relapse was based on a 30% increase in the SDS mean total score from Phase C Baseline, at least one SDS sub-score at 4 or greater, and an SDS total score ≥7 when all 3 sub-scores were available. The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0=not at all, to 10=extremely. Higher scores of 5 and above are associated with significant functional impairment.
Measured: Up to 14 days post last dose in Phase C (up to 28 weeks)
Phase C: Percentage of Participants Meeting Any Relapse Criteria
Relapse criteria included: At the same visit, increase in MADRS total score (10 items,7-point scale of 0=no symptoms to 6=severe symptoms, total score of 0 to 60) of 50% from randomization and CGI-S (8-point scale ranging from 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 item 10 of suicidality) or answer of yes on question 4 or 5 of C-SSRS (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 answer of yes to any question in suicidal behavior section (5 questions: preparatory acts/behavior, aborted attempt, interrupted attempt, actual attempt [non-fatal], completed suicide). Percentage of participants were rounded off to single decimal point.
Measured: Up to 26 weeks in Phase C
Phase C: Percentage of Participants Maintaining Remission
Participants maintaining remission was defined as MADRS total score ≤10. The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants were rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression.
Measured: 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
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants were rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A positive change from Baseline indicates worsening of symptoms. Baseline was defined as the last available assessment value in Phase B for this outcome measure. ANCOVA model was used for analysis.
Measured: Baseline and Week 46
Phase C: Change From Baseline for Randomization Phase in CGI-S Score at Week 46
The CGI -S was used to rate the severity of illness for each participant on an 8-point scale ranging from 0 to 7 where 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, and 7=among the most extremely ill participants. A positive change from Baseline indicates worsening of illness. Baseline was defined as the last available assessment value in Phase B for this outcome measure. ANCOVA model was used for analysis.
Measured: Baseline and Week 46
Phase C: Change From Baseline for Randomization Phase in Each of the SDS Individual Item Scores at Week 46
The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0=not at all, to 10=extremely. Higher scores of 5 and above are associated with significant functional impairment. A positive change from Baseline indicates worsening of symptoms impacting each area. Baseline was defined as the last available assessment value between Week 14 and Week 20 in Phase B for this outcome measure. ANCOVA model was used for analysis.
Measured: Baseline and Week 46
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2018
- Study start13 Jul 2018
- Primary completion8 Jul 2022
- Study completion29 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,149 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03538691
- Sponsor's protocol ID
- 331-201-00079
- Other IDs
- 2018-000601-22, 2018
- Status last verified
- Oct 2023
- First submitted
- 13 Apr 2018
- Last updated
- 12 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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. Small studies with less than 25 participants are excluded from data sharing.
Publications
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.
PubMed 39415650
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole as Adjunctive Therapy in the Maintenance Treatment of Adults With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT03538691
- Acronym / sponsor ID
- 331-201-00079
- Conditions
- Major Depressive Disorder
- Keywords
- Brexpiprazole, MDD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,149 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Jul 2018 (actual)
- Primary completion
- 8 Jul 2022 (actual)
- Study completion
- 29 Jul 2022 (actual)
- First posted
- 29 May 2018 (actual)
- Results
- Posted 12 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase A: Brexpiprazole + ADT | Experimental | Drug: Brexpiprazole, Drug: Antidepressant therapyParticipants 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. |
| Phase B: Brexpiprazole + ADT | Experimental | Drug: Brexpiprazole, Drug: Antidepressant therapyEligible 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. |
| Phase C: Brexpiprazole + ADT | Experimental | Drug: Brexpiprazole, Drug: Antidepressant therapyEligible 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. |
| Phase C: Placebo + ADT | Experimental | Drug: Antidepressant therapyEligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (36 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrexpiprazoleAlso: OPC-34712, RexultiAdministered as tablets. | Drug | Phase A: Brexpiprazole + ADT, Phase B: Brexpiprazole + ADT, Phase C: Brexpiprazole + ADT |
| Antidepressant therapyProtocol-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. | Drug | Phase A: Brexpiprazole + ADT, Phase B: Brexpiprazole + ADT, Phase C: Brexpiprazole + ADT, Phase C: Placebo + ADT |
Primary outcome
Phase C: Time-to-Relapse by Any Criteria as Defined in Blinded Addendum
Time frame: Up to 14 days post last dose in Phase C (up to 28 weeks)
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).
7 secondary outcomes
Phase C: Change From Baseline for Randomization Phase in Sheehan Disability Scale (SDS) Mean Total Score at Week 46
Time frame: Baseline and Week 46
Phase C: Time-to-functional Relapse Based on SDS Criteria
Time frame: Up to 14 days post last dose in Phase C (up to 28 weeks)
Phase C: Percentage of Participants Meeting Any Relapse Criteria
Time frame: Up to 26 weeks in Phase C
Phase C: Percentage of Participants Maintaining Remission
Time frame: 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
Time frame: Baseline and Week 46
Phase C: Change From Baseline for Randomization Phase in CGI-S Score at Week 46
Time frame: Baseline and Week 46
Phase C: Change From Baseline for Randomization Phase in Each of the SDS Individual Item Scores at Week 46
Time frame: Baseline and Week 46
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39415650McIntyre 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.
- Individual participant dataSharing planned: Yes. 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. Small studies with less than 25 participants are excluded from data sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brexpiprazole and Antidepressant therapy in people with Major Depressive Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase C: Time-to-Relapse by Any Criteria as Defined in Blinded Addendum (time frame: Up to 14 days post last dose in Phase C (up to 28 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03538691, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2023; AzTrials last refreshed its copy on 7 Nov 2026.