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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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ClinicalTrials.gov Identifier: NCT01727726
Recruitment Status : Completed
First Posted : November 16, 2012
Results First Posted : June 8, 2018
Last Update Posted : June 8, 2018
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

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.

Condition or disease Intervention/treatment Phase
Depressive Disorder Depression Depressive Disorder, Major Mood Disorders Mental Disorders Drug: Brexpiprazole Drug: Seroquel XR Drug: Placebo Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2182 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : December 2012
Actual Primary Completion Date : October 17, 2016
Actual Study Completion Date : November 10, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo + ADT
Matching Placebo and assigned ADT
Drug: Placebo
tablet/capsule

Experimental: Brexpiprazole + ADT
Brexpiprazole, flexible dose and assigned ADT
Drug: Brexpiprazole
tablet/capsule
Other Name: OPC-34712

Active Comparator: Seroquel XR + ADT
Seroquel XR, flexible dose and assigned ADT
Drug: Seroquel XR
tablet/capsule




Primary Outcome Measures :
  1. Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16). ]
    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 :
  1. Sheehan Disability Scale (SDS) [ Time Frame: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16). ]
    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.

  2. Change From End of Phase A in MADRS Total Score for Trial Week 2 and Week 4. [ Time Frame: Change from baseline to week 2 and week 4 in Phase B (week 10/12 and week 12/14) ]
    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.

  3. Clinical Global Impression Score [ Time Frame: From randomization to Phase B week 6 (14/16 weeks after randomization). ]
    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).

  4. MADRS Response at Week 6 [ Time Frame: Phase B week 6 (14/16 weeks after randomization). ]
    MADRS Response Rate, where response was defined as 50% reduction in MADRS Total Score, during double-blind randomized Phase B treatment.

  5. Number of Participants With MADRS [ Time Frame: Phase B week 6 (14/16 weeks after randomization). ]
    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.

  6. CGI-I Response Rate [ Time Frame: Phase B week 6 (14/16 weeks after randomization). ]
    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.

  7. Number of Participants With Adverse Events [ Time Frame: From screening (Day -28 to Day-1) upto post treatment follow-up. ]
    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.

  8. Sheehan Disability Scale (SDS) Individual Item Scores. [ Time Frame: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16). ]
    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).



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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:

  • 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.

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): NCT01727726


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Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Mary Hobart Otsuka Pharmaceutical Development & Commercialization, Inc.

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01727726     History of Changes
Other Study ID Numbers: 331-12-282
First Posted: November 16, 2012    Key Record Dates
Results First Posted: June 8, 2018
Last Update Posted: June 8, 2018
Last Verified: May 2018

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
OPC-34712
brexpiprazole
Major Depressive Disorder
Adjunctive Treatment

Additional relevant MeSH terms:
Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Mental Disorders
Psychotic Disorders
Mood Disorders
Pathologic Processes
Behavioral Symptoms
Schizophrenia Spectrum and Other Psychotic Disorders
Quetiapine Fumarate
Brexpiprazole
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Agonists
Dopamine Agents