Back to resultsA Study of Flexible-dose Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial
Primary Purpose
Depressive Disorder, Depression, Depressive Disorder, Major
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Brexpiprazole
Seroquel XR
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Depressive Disorder focused on measuring OPC-34712, brexpiprazole, Major Depressive Disorder, Adjunctive Treatment
Eligibility Criteria
Inclusion Criteria:
- Male and female outpatients 18 to 65 years of age, inclusive, at the time of informed consent.
- Subjects with both a diagnosis of MDD, and in a current major depressive episode, as defined by DSM-IV-TR criteria
- 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 during screening prior to receiving trial medication
- Subject has a current Axis I (DSM-IV-TR) diagnosis of: dementia, Schizophrenia, Bipolar, Eating disorder , Obsessive-compulsive disorder, Panic disorder, Posttraumatic stress disorder
- Subjects experiencing hallucinations, delusions or any psychotic symptomatology in the current major depressive episode.
- Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days
- Subjects currently treated with insulin for diabetes.
- Subjects with uncontrolled hypertension
- Subjects with known ischemic heart disease or history of myocardial infarction, congestive heart failure, angioplasty, stenting, or coronary artery bypass Surgery
- Subjects with a positive drug screen for cocaine, marijuana, or other illicit drugs
- Inability to swallow tablets or tolerate oral medication
- Abnormal laboratory test results, vital signs and ECG results
- Subjects who previously participated in any prior brexpiprazole clinical trial.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Active Comparator
Arm Label
Placebo + ADT
Brexpiprazole + ADT
Seroquel XR + ADT
Arm Description
Matching Placebo and assigned ADT
Brexpiprazole, flexible dose and assigned ADT
Seroquel XR, flexible dose and assigned ADT
Outcomes
Primary Outcome Measures
Montgomery Asberg Depression Rating Scale (MADRS)
To determine the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy by assessment of MADRS total score. The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.
Secondary Outcome Measures
Sheehan Disability Scale (SDS)
To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale is a measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains ( work/social life/family life/home responsibilities). 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. Scores of 5 and above are associated with significant functional impairment. Additionally, SDS included 2 questions related to productivity losses due to the psychiatric symptoms and impairment.
Change From End of Phase A in MADRS Total Score for Trial Week 2 and Week 4.
Change from end of Phase A in MADRS Total Score. The MADRS was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.
Clinical Global Impression Score
Mean change from end of Phase A in Clinical Global Impression - Severity of Illness scale (CGI-S) score and Improvement scale (CGI-I) during double-blind randomized Phase B treatment. CGI-S score assessed how mentally ill the patient was at that time. CGI-S score is calculated from 0 to 7 (0 indicates not assessed 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and7 indicated among the most extremely ill patient). CGI-I score is compared to his/her condition at baseline, how much has the patient changed. CGI-I score is calculated from 0 to 7 (0 indicates not assessed and 7 indicates very much worse).
MADRS Response at Week 6
MADRS Response Rate, where response was defined as 50% reduction in MADRS Total Score, during double-blind randomized Phase B treatment.
Number of Participants With MADRS
MADRS Remission Rate, where remission was defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score, for every trial week visit during double-blind randomized Phase B treatment.
CGI-I Response Rate
CGI-I Response rate, where response was defined as a CGI-I score of 1 or 2 (very much improved or much improved), during double-blind randomized Phase B treatment.
Number of Participants With Adverse Events
To evaluate the safety and tolerability of brexpiprazole (flexible dose) as adjunctive therapy to ADT in the proposed subject population with MDD as AE variables.
Sheehan Disability Scale (SDS) Individual Item Scores.
To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale (a self rated questionnaire) was used for measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains (work/school work, social life/leisure activities and family life/home responsibilities). All domains were rated on a score scale ranged from 0 (no impairment) to 10 (most severe). Score of 5 and above indicated significant functional impairment. A total score was addition of the 3 individual scores and the total score ranged from 0 (no impairment) to 30 (most severe).
Full Information
NCT ID
NCT01727726
First Posted
October 31, 2012
Last Updated
May 10, 2018
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01727726
Brief Title
A Study of Flexible-dose Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial
Official Title
A Phase 3, Multicenter, Randomized, Double-blind, Placebo and Active Comparator Controlled Trial of Flexible-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
October 17, 2016 (Actual)
Study Completion Date
November 10, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To compare the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy to an assigned open label antidepressant therapy (ADT) in the proposed subject population with MDD.
Detailed Description
This is a trial designed to assess the safety and efficacy of brexpiprazole (flexible dose) as adjunctive therapy to an assigned known anti-depressant in depressed subjects. The trial consists of a continuous 18-week double-blind treatment period with a 30-day follow-up. Subjects who complete all trial visits through the Week 18 visit may be offered entry into an optional open-label rollover trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder, Depression, Depressive Disorder, Major, Mood Disorders, Mental Disorders
Keywords
OPC-34712, brexpiprazole, Major Depressive Disorder, Adjunctive Treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2182 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo + ADT
Arm Type
Placebo Comparator
Arm Description
Matching Placebo and assigned ADT
Arm Title
Brexpiprazole + ADT
Arm Type
Experimental
Arm Description
Brexpiprazole, flexible dose and assigned ADT
Arm Title
Seroquel XR + ADT
Arm Type
Active Comparator
Arm Description
Seroquel XR, flexible dose and assigned ADT
Intervention Type
Drug
Intervention Name(s)
Brexpiprazole
Other Intervention Name(s)
OPC-34712
Intervention Description
tablet/capsule
Intervention Type
Drug
Intervention Name(s)
Seroquel XR
Intervention Description
tablet/capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
tablet/capsule
Primary Outcome Measure Information:
Title
Montgomery Asberg Depression Rating Scale (MADRS)
Description
To determine the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy by assessment of MADRS total score. The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.
Time Frame
Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).
Secondary Outcome Measure Information:
Title
Sheehan Disability Scale (SDS)
Description
To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale is a measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains ( work/social life/family life/home responsibilities). 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. Scores of 5 and above are associated with significant functional impairment. Additionally, SDS included 2 questions related to productivity losses due to the psychiatric symptoms and impairment.
Time Frame
Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).
Title
Change From End of Phase A in MADRS Total Score for Trial Week 2 and Week 4.
Description
Change from end of Phase A in MADRS Total Score. The MADRS was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.
Time Frame
Change from baseline to week 2 and week 4 in Phase B (week 10/12 and week 12/14)
Title
Clinical Global Impression Score
Description
Mean change from end of Phase A in Clinical Global Impression - Severity of Illness scale (CGI-S) score and Improvement scale (CGI-I) during double-blind randomized Phase B treatment. CGI-S score assessed how mentally ill the patient was at that time. CGI-S score is calculated from 0 to 7 (0 indicates not assessed 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and7 indicated among the most extremely ill patient). CGI-I score is compared to his/her condition at baseline, how much has the patient changed. CGI-I score is calculated from 0 to 7 (0 indicates not assessed and 7 indicates very much worse).
Time Frame
From randomization to Phase B week 6 (14/16 weeks after randomization).
Title
MADRS Response at Week 6
Description
MADRS Response Rate, where response was defined as 50% reduction in MADRS Total Score, during double-blind randomized Phase B treatment.
Time Frame
Phase B week 6 (14/16 weeks after randomization).
Title
Number of Participants With MADRS
Description
MADRS Remission Rate, where remission was defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score, for every trial week visit during double-blind randomized Phase B treatment.
Time Frame
Phase B week 6 (14/16 weeks after randomization).
Title
CGI-I Response Rate
Description
CGI-I Response rate, where response was defined as a CGI-I score of 1 or 2 (very much improved or much improved), during double-blind randomized Phase B treatment.
Time Frame
Phase B week 6 (14/16 weeks after randomization).
Title
Number of Participants With Adverse Events
Description
To evaluate the safety and tolerability of brexpiprazole (flexible dose) as adjunctive therapy to ADT in the proposed subject population with MDD as AE variables.
Time Frame
From screening (Day -28 to Day-1) upto post treatment follow-up.
Title
Sheehan Disability Scale (SDS) Individual Item Scores.
Description
To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale (a self rated questionnaire) was used for measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains (work/school work, social life/leisure activities and family life/home responsibilities). All domains were rated on a score scale ranged from 0 (no impairment) to 10 (most severe). Score of 5 and above indicated significant functional impairment. A total score was addition of the 3 individual scores and the total score ranged from 0 (no impairment) to 30 (most severe).
Time Frame
Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female outpatients 18 to 65 years of age, inclusive, at the time of informed consent.
Subjects with both a diagnosis of MDD, and in a current major depressive episode, as defined by DSM-IV-TR criteria
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 during screening prior to receiving trial medication
Subject has a current Axis I (DSM-IV-TR) diagnosis of: dementia, Schizophrenia, Bipolar, Eating disorder , Obsessive-compulsive disorder, Panic disorder, Posttraumatic stress disorder
Subjects experiencing hallucinations, delusions or any psychotic symptomatology in the current major depressive episode.
Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days
Subjects currently treated with insulin for diabetes.
Subjects with uncontrolled hypertension
Subjects with known ischemic heart disease or history of myocardial infarction, congestive heart failure, angioplasty, stenting, or coronary artery bypass Surgery
Subjects with a positive drug screen for cocaine, marijuana, or other illicit drugs
Inability to swallow tablets or tolerate oral medication
Abnormal laboratory test results, vital signs and ECG results
Subjects who previously participated in any prior brexpiprazole clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary Hobart
Organizational Affiliation
Otsuka Pharmaceutical Development & Commercialization, Inc.
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Phoenix
State/Province
Arizona
Country
United States
City
Little Rock
State/Province
Arkansas
Country
United States
City
Bellflower
State/Province
California
Country
United States
City
Beverly Hills
State/Province
California
Country
United States
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92626
Country
United States
City
Glendale
State/Province
California
Country
United States
City
Irvine
State/Province
California
Country
United States
City
Redlands
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
Upland
State/Province
California
Country
United States
City
Gainesville
State/Province
Florida
Country
United States
City
Jacksonville Beach
State/Province
Florida
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Leesburg
State/Province
Florida
Country
United States
City
Melbourne
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33015
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33145
Country
United States
City
Oakland Park
State/Province
Florida
Country
United States
City
Orange City
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Decatur
State/Province
Georgia
Country
United States
City
Lake Charles
State/Province
Louisiana
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Belmont
State/Province
Massachusetts
Country
United States
City
Roslindale
State/Province
Massachusetts
Country
United States
City
Watertown
State/Province
Massachusetts
ZIP/Postal Code
02472
Country
United States
City
Creve Coeur
State/Province
Missouri
Country
United States
City
Lebanon
State/Province
New Hampshire
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10168
Country
United States
City
Columbus
State/Province
Ohio
Country
United States
City
Dayton
State/Province
Ohio
Country
United States
City
Edmond
State/Province
Oklahoma
ZIP/Postal Code
73013
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Salem
State/Province
Oregon
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Murray
State/Province
Utah
Country
United States
City
Herndon
State/Province
Virginia
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Bellevue
State/Province
Washington
Country
United States
City
Kirkland
State/Province
Washington
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Brown Deer
State/Province
Wisconsin
Country
United States
City
Penticton
State/Province
British Columbia
Country
Canada
City
Dijon
Country
France
City
Douai
Country
France
City
Elancourt
Country
France
City
Jarnac
Country
France
City
Montepellier
Country
France
City
Orvault
Country
France
City
Achim
Country
Germany
City
Mittweida
Country
Germany
City
Stralsund
Country
Germany
City
Wuerzburg
Country
Germany
City
Belchatow
Country
Poland
City
Bydgoszcz
Country
Poland
City
Gdynia
Country
Poland
City
Kielce
Country
Poland
City
Lublin
Country
Poland
City
Tuszyn
Country
Poland
City
Wroclaw
Country
Poland
City
Arkhangelsk
ZIP/Postal Code
163530
Country
Russian Federation
City
Moscow
ZIP/Postal Code
107076
Country
Russian Federation
City
Moscow
ZIP/Postal Code
127083
Country
Russian Federation
City
Saint-Petersburg
ZIP/Postal Code
190020
Country
Russian Federation
City
Saint-Petersburg
ZIP/Postal Code
191040
Country
Russian Federation
City
Saint-Petersburg
ZIP/Postal Code
192019
Country
Russian Federation
City
Saint-Petersburg
ZIP/Postal Code
199034
Country
Russian Federation
City
Smolensk
Country
Russian Federation
City
Tonnelniy
Country
Russian Federation
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
City
Belgrade
Country
Serbia
City
Kragujevac
Country
Serbia
City
Nis
Country
Serbia
City
Novi Knezevac
Country
Serbia
12. IPD Sharing Statement
Citations:
PubMed Identifier
31577867
Citation
Newcomer JW, Eriksson H, Zhang P, Meehan SR, Weiss C. Changes in Metabolic Parameters and Body Weight in Patients With Major Depressive Disorder Treated With Adjunctive Brexpiprazole: Pooled Analysis of Phase 3 Clinical Studies. J Clin Psychiatry. 2019 Oct 1;80(6):18m12680. doi: 10.4088/JCP.18m12680.
Results Reference
derived
PubMed Identifier
30508090
Citation
Hobart M, Zhang P, Weiss C, Meehan SR, Eriksson H. Adjunctive Brexpiprazole and Functioning in Major Depressive Disorder: A Pooled Analysis of Six Randomized Studies Using the Sheehan Disability Scale. Int J Neuropsychopharmacol. 2019 Mar 1;22(3):173-179. doi: 10.1093/ijnp/pyy095.
Results Reference
derived
Learn more about this trial
A Study of Flexible-dose Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial
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