Major Depressive Disorder (MDD)Phase 3NCT02012218

Brexpiprazole as Adjunctive Therapy With Major Depressive Disorder and an Inadequate Response to Previous Adjunctive Therapy

A Phase 3 study testing ADT and Brexpiprazole in people with Major Depressive Disorder (MDD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 24 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The objectives of this exploratory trial are to evaluate the efficacy, safety, and subjects' subjective satisfaction when switching to adjunctive brexpiprazole in subjects with MDD who have responded inadequately to preceding adjunctive drug therapy. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Major Depressive Disorder (MDD)
What is being tested?: ADT and Brexpiprazole
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 61 participants
Where: 24 sitesUnited States
Study dates: Nov 2013to Oct 2014
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

Clinical diagnosis of MDD
In current major depressive episode of ≥ 8 weeks in duration and includes an inadequate response to at least 1 adjunctive treatment.
Positive history of at least 1 additional failure to an adequate monotherapy antidepressant treatment.
HAM-D17 total score≥ 18
Currently receiving SSRI of SNRI with adjunctive treatment for at least 6 weeks before screening.
Willing to discontinue use of all prohibited psychotropic medications

Show all 9Show fewer

Historical positive serological results for HIV, hepatitis B/C
Able to provide written informed consent prior to the initiation of any protocol-required procedures
Subjects who could potentially benefit from adjunctive treatment with Brexpiprazole

Who cannot join

Sexually active women of childbearing potential
Male subjects not practicing 2 different methods of birth control
Females who are breastfeeding and/or who have a positive pregnancy test result
Subjects who have received ECT for the current major depressive episode.
Subjects who have had an inadequate response to ECT
Current need for involuntary commitment or who have been hospitalized within 4 weeks of screening

Show all 40Show fewer

Current Axis I (DSM-IV-TR)
Current Axis II (DSM-IV-TR)
Subjects experiencing hallucinations, delusions, or any psychotic symptomatology in the current major depressive episode.
Subjects receiving new onset psychotherapy.
Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 4, Item 5, or on any of the 5 C-SSRS Suicidal Behavior Items
Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days
Hypothyroidism or hyperthyroidism
Clinically significant neurological, hepatic, renal, metabolic, haematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders
Currently treated with insulin for diabetes
Uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension
Known ischemic heart disease or history of myocardial infarction, congestive heart failure, angioplasty, stenting, or coronary artery bypass surgery
Epilepsy or history of seizures
Positive drug screen
The following laboratory test and ECG results are exclusionary:
Platelets ≤ 75,000/mm3
Hemoglobin ≤ 9 g/dL
Neutrophils, absolute ≤ 1000/mm3
AST > 2 × ULN
ALT > 2 × ULN
CPK > 3 × ULN, unless discussed with and approved by the medical monitor
Creatinine ≥ 2 mg/dL
HbA1c ≥ 7.0%
Abnormal free T4 (Note: Free T4 is measured only if result for TSH is abnormal.)
QTcF ≥ 470 msec for females and ≥ 450 msec for males
Treatment with an MAOI or EMSAM within 14 days of the Baseline visit.
Use of benzodiazepines and/or hypnotics within 7 days prior to the first dose of IMP
Use of oral neuroleptics within 7 days prior or long-acting approved atypical antipsychotics ≤ 1 full cycle plus ½ cycle prior to the first dose of IMP
Subjects who would be likely to require prohibited concomitant therapy during the trial.
Subjects who previously participated in any prior brexpiprazole trial
History of neuroleptic malignant syndrome or serotonin syndrome
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 a clinical trial within the last 180 days or who participated in more than 2 clinical trials within the past year.
Any subject who, in the opinion of the investigator or medical monitor, should not participate.

Trial locations and contacts

24 sites in 1 country.

City, postcode or hospital

24 sites in 1 country

United States24 sites

Lehigh Center for Clinical Research
Allentown, Pennsylvania, 18104
Pharmasite Research
Baltimore, Maryland, 21208
Boston Clinical Trials
Boston, Massachusetts, 02131
Center for Emotional Fitness
Cherry Hill, New Jersey, 08002
Future Search Trials of Dallas, LP
Dallas, Texas, 75231
Midwest Clinical Research Center MCRC
Dayton, Ohio, 45417-3445
Collaborative NeuroScience Network, Inc.
Garden Grove, California, 92845
Goldpoint Clinical Research
Indianapolis, Indiana, 46260
Alpine Clinic
Lafayette, Indiana, 47905
Lincoln Research, LLC
Lincoln, Rhode Island, 02865
Research Strategies of Memphis, LLC
Memphis, Tennessee, 38119
Cutting Edge Research Group
Oklahoma City, Oklahoma, 73116
Clinical Neuroscience Solutions Pharmacology
Orlando, Florida, 32806
Oregon Center for Clinical Investigations, Inc.
Portland, Oregon, 97210
Richard H. Weisler, MD, PA
Raleigh, North Carolina, 27609
Rochester Center for Behavioral Medicine
Rochester Hills, Michigan, 48307
Oregon Center for Clinical Investigations, Inc.
Salem, Oregon, 97301
Carman Research
Smyrna, Georgia, 30080
Frontier Institute
Spokane, Washington, 99204
St. Louis Clinical Trials
St Louis, Missouri, 63118
Behavioral Medical Research of Staten Island
Staten Island, New York, 10305
Viking Clinical Research, Ltd.
Temecula, California, 92591
Coastal Research Associates, Inc.
Weymouth, Massachusetts, 02190
NeuropsychiatricAssociates
Woodstock, Vermont, 05091

Other trials in United States

About this study

Official title: A Phase 3b, Multicenter, Open-label Exploratory Trial to Evaluate the Efficacy, Safety, and Subject Satisfaction With Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder and an Inadequate Response to Previous Adjunctive Therapy

Conditions: Major Depressive Disorder (MDD)
Being tested: ADT, Brexpiprazole
Keywords: Major Depressive Disorder, Depression
Medical subject headings: Depressive Disorder, Major, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ADTDrug
BrexpiprazoleDrug

Study groups in NCT02012218
Study group	Role	What they receive
ADT and Brexpiprazole	Experimental	ADT and Brexpiprazole Receives: Drug: ADT; Drug: Brexpiprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
The MADRS was used as the primary efficacy assessment of level of depression. The MADRS was administered using the Structured Interview Guide for the MADRS. Detailed instructions were provided.The MADRS consists of 10 items each, with 7 defined grades of severity (ie, 0 to 6, with 0 being the "best" rating and 6 being the "worst" rating). The MADRS total score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score least squares (LS) mean changes from baseline to Week 6 is mentioned below.
Measured: Baseline and Week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2013Oct 2014

First posted16 Dec 2013 (estimated)
Study startNov 2013
Primary completionOct 2014
Study completionOct 2014

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 (2)Papers the sponsor has linked to this study.
Other trials for Major Depressive Disorder (MDD)Studies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 61 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02012218
Sponsor's protocol ID: 331-13-001
Status last verified: Nov 2015
First submitted: 4 Dec 2013
Last updated: 29 Dec 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Weiss C, Meehan SR, Brown TM, Gupta C, Morup MF, Thase ME, McIntyre RS, Ismail Z. Effects of adjunctive brexpiprazole on calmness and life engagement in major depressive disorder: post hoc analysis of patient-reported outcomes from clinical trial exit interviews. J Patient Rep Outcomes. 2021 Dec 11;5(1):128. doi: 10.1186/s41687-021-00380-4.
PubMed 34894307
Fava M, Okame T, Matsushima Y, Perry P, Weiller E, Baker RA. Switching from Inadequate Adjunctive or Combination Treatment Options to Brexpiprazole Adjunctive to Antidepressant: An Open-Label Study on the Effects on Depressive Symptoms and Cognitive and Physical Functioning. Int J Neuropsychopharmacol. 2017 Jan 1;20(1):22-30. doi: 10.1093/ijnp/pyw087.
PubMed 27784751

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 29 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3b, Multicenter, Open-label Exploratory Trial to Evaluate the Efficacy, Safety, and Subject Satisfaction With Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder and an Inadequate Response to Previous Adjunctive Therapy
ClinicalTrials.gov ID: NCT02012218
Acronym / sponsor ID: 331-13-001
Conditions: Major Depressive Disorder (MDD)
Keywords: Major Depressive Disorder, Depression
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 61 participants (actual)
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
Collaborators: Otsuka Pharmaceutical Co., Ltd.
Study start: Nov 2013
Primary completion: Oct 2014 (actual)
Study completion: Oct 2014 (actual)
First posted: 16 Dec 2013 (estimated)
Results: Posted 8 Oct 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
ADT and Brexpiprazole	Experimental	Drug: ADT, Drug: BrexpiprazoleADT and Brexpiprazole

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Clinical diagnosis of MDD
In current major depressive episode of ≥ 8 weeks in duration and includes an inadequate response to at least 1 adjunctive treatment.
Positive history of at least 1 additional failure to an adequate monotherapy antidepressant treatment.
HAM-D17 total score≥ 18
Currently receiving SSRI of SNRI with adjunctive treatment for at least 6 weeks before screening.

Key exclusion criteria (40 listed)

Sexually active women of childbearing potential
Male subjects not practicing 2 different methods of birth control
Females who are breastfeeding and/or who have a positive pregnancy test result
Subjects who have received ECT for the current major depressive episode.
Subjects who have had an inadequate response to ECT

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
ADT	Drug	ADT and Brexpiprazole
Brexpiprazole	Drug	ADT and Brexpiprazole

Primary outcome

Mean Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Time frame: Baseline and Week 6
The MADRS was used as the primary efficacy assessment of level of depression. The MADRS was administered using the Structured Interview Guide for the MADRS. Detailed instructions were provided.The MADRS consists of 10 items each, with 7 defined grades of severity (ie, 0 to 6, with 0 being the "best" rating and 6 being the "worst" rating). The MADRS total score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score least squares (LS) mean changes from baseline to Week 6 is mentioned below.

Results and safety

Results posted to the registry on 8 Oct 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1A	12	8
Group 1B	11	10
Group 2	13	11
Group 3	19	17
Group 4	6	5

Primary outcome: Mean Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

Time frame: Baseline and Week 6. Least squares mean (Standard Error). Unit: Units on a scale

Measure	Group 1A n = 12	Group 1B n = 10	Group 2 n = 12	Group 3 n = 19	Group 4 n = 6
Value	-12.8 (2.26)	-18.4 (2.10)	-19.5 (1.99)	-19.2 (1.59)	-16.8 (2.97)

Group 1A vs Group 1B vs Group 2 vs Group 3 vs Group 4: p <0.0001, Mixed Models Analysis

Population analysed: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid post-baseline efficacy assessment.

Adverse events

Time frame: Adverse events were reported from the signing of the informed consent until the end of trial with a safety follow-up of 30 (+2 ) days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1A	0 of 12 (0%)	7 of 12 (58.3%)	Not reported
Group 1B	1 of 11 (9.1%)	8 of 11 (72.7%)	Not reported
Group 2	0 of 13 (0%)	6 of 13 (46.2%)	Not reported
Group 3	0 of 19 (0%)	15 of 19 (78.9%)	Not reported
Group 4	0 of 6 (0%)	5 of 6 (83.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34894307Weiss C, Meehan SR, Brown TM, Gupta C, Morup MF, Thase ME, McIntyre RS, Ismail Z. Effects of adjunctive brexpiprazole on calmness and life engagement in major depressive disorder: post hoc analysis of patient-reported outcomes from clinical trial exit interviews. J Patient Rep Outcomes. 2021 Dec 11;5(1):128. doi: 10.1186/s41687-021-00380-4.
Derived from this study: PubMed 27784751Fava M, Okame T, Matsushima Y, Perry P, Weiller E, Baker RA. Switching from Inadequate Adjunctive or Combination Treatment Options to Brexpiprazole Adjunctive to Antidepressant: An Open-Label Study on the Effects on Depressive Symptoms and Cognitive and Physical Functioning. Int J Neuropsychopharmacol. 2017 Jan 1;20(1):22-30. doi: 10.1093/ijnp/pyw087.

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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.

Junichi Hashimoto, PhD study director

Otsuka Pharmaceutical Co., Ltd Japan (OPCJ)

24 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ADT and Brexpiprazole in people with Major Depressive Disorder (MDD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 24 sites 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 9 inclusion and 40 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 29 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites 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 8 Oct 2015). 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?

Mean Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (time frame: Baseline and Week 6). 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 NCT02012218, which also lists 2 linked publications.

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 29 Dec 2015.