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

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ClinicalTrials.gov Identifier: NCT03538691

Recruitment Status : Recruiting

First Posted : May 28, 2018

Last Update Posted : September 3, 2018

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Sponsor:

Information provided by (Responsible Party):

Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Brexpiprazole Drug: Placebo Drug: Citalopram Hydrobromide Drug: Escitalopram Drug: Fluoxetine Drug: Paroxetine Drug: Sertraline Drug: Duloxetine Drug: Venlafaxine Extended Release Oral Capsule	Phase 3

Study Design


Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	1450 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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
Actual Study Start Date :	July 13, 2018
Estimated Primary Completion Date :	September 2022
Estimated Study Completion Date :	September 2022

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Depression

Drug Information available for: Brexpiprazole

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Brexpiprazole & Citalopram Hydrobromide Brexpiprazole: oral tablet; 2 to 3 mg/day Citalopram hydrobromide: oral tablet; 20 or 40 mg/day	Drug: Brexpiprazole Tablet Other Name: OPC-34712 Drug: Citalopram Hydrobromide Tablet Other Name: Celexa
Placebo Comparator: Placebo & Citalopram Hydrobromide Placebo: daily oral tablet Citalopram hydrobromide: oral tablet; 20 or 40 mg/day	Drug: Placebo Tablet Drug: Citalopram Hydrobromide Tablet Other Name: Celexa
Experimental: Brexpiprazole & Escitalopram Brexpiprazole: oral tablet; 2 to 3 mg/day Escitalopram: oral tablet; 10 or 20 mg/day	Drug: Brexpiprazole Tablet Other Name: OPC-34712 Drug: Escitalopram Tablet Other Name: Lexapro
Placebo Comparator: Placebo & Escitalopram Placebo: daily oral tablet Escitalopram: oral tablet; 10 or 20 mg/day	Drug: Placebo Tablet Drug: Escitalopram Tablet Other Name: Lexapro
Experimental: Brexpiprazole & Fluoxetine Brexpiprazole: oral tablet; 2 to 3 mg/day Fluoxetine: oral capsule; 20 or 40 mg/day	Drug: Brexpiprazole Tablet Other Name: OPC-34712 Drug: Fluoxetine Capsules Other Name: Prozac
Placebo Comparator: Placebo & Fluoxetine Placebo: daily oral tablet Fluoxetine: oral capsule; 20 or 40 mg/day	Drug: Placebo Tablet Drug: Fluoxetine Capsules Other Name: Prozac
Experimental: Brexpiprazole & Paroxetine Brexpiprazole: oral tablet; 2 to 3 mg/day Paroxetine: oral controlled-release tablet; 37.5 or 50 mg/day	Drug: Brexpiprazole Tablet Other Name: OPC-34712 Drug: Paroxetine Controlled-release tablets Other Name: Paxil CR
Placebo Comparator: Placebo & Paroxetine Placebo: daily oral tablet Paroxetine: oral controlled-release tablet; 37.5 or 50 mg/day	Drug: Placebo Tablet Drug: Paroxetine Controlled-release tablets Other Name: Paxil CR
Experimental: Brexpiprazole & Sertraline Brexpiprazole: oral tablet; 2 to 3 mg/day Sertraline: oral tablet; 100, 150 or 200 mg/day	Drug: Brexpiprazole Tablet Other Name: OPC-34712 Drug: Sertraline Tablet Other Name: Zoloft
Placebo Comparator: Placebo & Sertraline Placebo: daily oral tablet Sertraline: oral tablet; 100, 150 or 200 mg/day	Drug: Placebo Tablet Drug: Sertraline Tablet Other Name: Zoloft
Experimental: Brexpiprazole & Duloxetine Brexpiprazole: oral tablet; 2 to 3 mg/day Duloxetine: oral delayed-release capsule; 40 or 60 mg/day	Drug: Brexpiprazole Tablet Other Name: OPC-34712 Drug: Duloxetine Delayed-release capsule Other Name: Cymbalta
Placebo Comparator: Placebo & Duloxetine Placebo: daily oral tablet Duloxetine: oral delayed-release capsule; 40 or 60 mg/day	Drug: Placebo Tablet Drug: Duloxetine Delayed-release capsule Other Name: Cymbalta
Experimental: Brexpiprazole & Venlafaxine extended-release (XR) Brexpiprazole: oral tablet; 2 to 3 mg/day Venlafaxine XR: daily extended-release capsule; 75, 150, or 225 mg/day	Drug: Brexpiprazole Tablet Other Name: OPC-34712 Drug: Venlafaxine Extended Release Oral Capsule Extended-release capsule Other Name: Effexor XR
Placebo Comparator: Placebo & Venlafaxine extended-release (XR) Placebo: daily oral tablet Venlafaxine XR: daily extended-release capsule; 75, 150, or 225 mg/day	Drug: Placebo Tablet Drug: Venlafaxine Extended Release Oral Capsule Extended-release capsule Other Name: Effexor XR

Outcome Measures

Primary Outcome Measures :

Time-to-Relapse in symptoms of Major Depressive Disorder (MDD) [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to week 46 or early termination ]
Assessed with Montgomery Asberg Depression Rating Scale (MADRS). Scale ranges from 0 to 60 with a higher score indicating worsening symptoms of depression.
Time-to-Relapse in symptoms of Major Depressive Disorder (MDD) [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to week 46 or early termination ]
Assessed with Clinical Global Impression - Severity of Illness (CGI-S) Results. Score ranges from 1 to 7, with a score of 7 being a worse outcome than a score of 1.

Secondary Outcome Measures :

Change from Phase A baseline in Sheehan Disability Scale (SDS) mean total score at Week 46 [ Time Frame: Up to 46 weeks; from baseline visit at Day 1 to week 46 or early termination ]
When applicable, the change from phase A baseline in SDS mean total score to the last observation carried forward (week 46). Score ranges from 0 to 10, with a score of 10 being worse than a score of 0.
Time-to-Functional Relapse in symptoms of MDD [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Assessed with Sheehan Disability Scale. Score ranges from 0 to 10, with a score of 10 being worse than a score of 0.
Time-to-Relapse in symptoms of MDD [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Assessed with MADRS criteria. Scale ranges from 0 to 60 with a higher score indicating worsening symptoms of depression.
Time-to-Relapse in symptoms of MDD [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Assessed with CGI-S criteria. Score ranges from 1 to 7, with a score of 7 being a worse outcome than a score of 1.
Time-to-relapse in symptoms of MDD [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Assessed with hospitalization for depression
Time-to-Relapse in symptoms of MDD [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Assessed with lack of efficacy
Time-to-Relapse in symptoms of MDD [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Assessed with active suicidality
Percentage of subjects who relapsed based on MADRS criteria [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Scale ranges from 0 to 60 with a higher score indicating worsening symptoms of depression.
Percentage of subjects who relapsed based on CGI-S criteria [ Time Frame: Up to 26 weeks; from baseline visit to Week 46 or Early Termination ]
Score ranges from 1 to 7, with a score of 7 being a worse outcome than a score of 1.
Percentage of subjects who relapse by hospitalization for depression [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Percentage of subjects who relapsed by discontinuation due to lack of efficacy or worsening depression [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Percentage of subjects who relapsed by active suicidality [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Based upon MADRS and/or C-SSRS criteria
Percentage of subjects maintaining remission [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Mean change from randomization in MADRS total score [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Mean change from randomization in CGI-S score [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Change from randomization in each of the SDS individual item scores (LOCF) [ Time Frame: Up to 26 weeks; from baseline visit at Week 20 to Week 46 or Early Termination ]
Score ranges from 0 to 10, with a score of 10 being worse than a score of 0.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects 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.
Subjects must have reported a history for the current major depressive episode of an inadequate response to 1 or 2 adequate antidepressant treatments, and subjects must currently be taking a protocol-mandated antidepressant treatment at an adequate dose and duration, and most not have reported ≥ 50% improvement. For subjects 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 subjects 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)
Subjects with a Hamilton Rating Scale for Depression (HAM-D17) total score ≥ 18 at the screening visit, and Phase A baseline visits.
Subjects willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period.

Exclusion Criteria:

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.
Subjects who report treatment with adjunctive antipsychotic medication with an antidepressant for a minimum of 3 weeks during the current major depressive episode
Subjects who report allergies or an intolerability (lifetime treatment history) to trial-provided ADTs that have not been prescribed to the subject during the current major depressive episode.
Subjects who have received ECT for the current major depressive episode
Subjects 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. Subjects who have had transcranial magnetic stimulation during the current major depressive episode.
Subjects with a current need for involuntary commitment or who have been hospitalized within 4 weeks of screening for the current major depressive episode.
Subjects with a primary DSM-5 diagnosis of:
1. Schizophrenia Spectrum and Other Psychotic Disorders
2. Bipolar and Related Disorders
3. Obsessive Compulsive Disorders
4. Feeding and Eating Disorders
5. Neurocognitive Disorders
6. Panic Disorder
7. Post-Traumatic Stress Disorder
Subjects with a current DSM-5 diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder or intellectual disability.
Subjects experiencing hallucinations, delusions, or any psychotic symptomatology in the current major depressive episode
Subjects receiving new onset psychotherapy (individual, group, marriage or family therapy) within 42 days of screening or at any time during participation in the trial
Subjects 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
Subjects 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.
Subjects 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.
Subjects with diabetes mellitus (IDDM and non-IDDM) are ineligible for the trial unless their condition is stable and well-controlled.
Subjects with uncontrolled hypertension (DBP > 95 mmHg) or symptomatic hypotension, or orthostatic hypotension which is defined as a decrease of ≥ 30 mmHg in SBP and/or decrease of ≥ 20 mmHg in DBP after at least 3 minutes standing compared to the previous supine blood pressure OR development of symptoms.
Subjects with known ischemic heart disease or history of myocardial infarction-or congestive heart failure (whether controlled or uncontrolled)
Subjects with epilepsy or a history of seizures, except for a single seizure episode
Subjects 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 subject 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 subject or interpretation of the trial results, and participation is agreed to by the medical monitor prior to treatment.
Treatment with an 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.
Subjects who would be likely to require prohibited concomitant therapy during the trial.
Subjects who have been exposed to brexpiprazole in any prior clinical trial or has received commercial brexpiprazole (Rexulti).
Subjects with a history of neuroleptic malignant syndrome or serotonin syndrome.
Subjects with a history of true allergic response to more than one class of medications
Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
Subjects who participated in any clinical trial within the last 60 days or who participated in more than 2 clinical trials within the past year

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03538691

Contacts


Contact: Michelle Maldonado	+1(512)579-4744	michelle.maldonado@syneoshealth.com
Contact: Ananda Robes	+1(919)926-5692	ananda.robes@syneoshealth.com

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Sponsors and Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

More Information


Responsible Party:	Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:	NCT03538691 History of Changes
Other Study ID Numbers:	331-201-00079
First Posted:	May 28, 2018 Key Record Dates
Last Update Posted:	September 3, 2018
Last Verified:	August 2018


Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:


Brexpiprazole MDD

Additional relevant MeSH terms:


Disease Depressive Disorder Depression Depressive Disorder, Major Pathologic Processes Mood Disorders Mental Disorders Behavioral Symptoms Citalopram Sertraline Fluoxetine Paroxetine Venlafaxine Hydrochloride Duloxetine Hydrochloride Dexetimide	Brexpiprazole Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Serotonin Agents Physiological Effects of Drugs Antidepressive Agents, Second-Generation Antidepressive Agents Psychotropic Drugs Antiparkinson Agents Anti-Dyskinesia Agents Parasympatholytics Autonomic Agents

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