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Brexpiprazole (OPC-34712) as an Adjunctive Treatment in Adults With Major Depressive Disorder and Anxiety Symptoms

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ClinicalTrials.gov Identifier: NCT02013531
Recruitment Status : Completed
First Posted : December 17, 2013
Results First Posted : March 29, 2016
Last Update Posted : March 29, 2016
Sponsor:
Collaborator:
Otsuka Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary:
The purpose of this study is to investigate the efficacy and safety of flexibly dosed adjunctive brexpiprazole treatment in subjects with major depressive disorder and anxiety symptoms, who are experiencing an inadequate selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI) response.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Anxiety Drug: Brexpiprazole Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Protocol 331-13-002: An Exploratory, Multicenter, Open-label, Flexible-dose Trial of Brexpiprazole (OPC-34712) as an Adjunctive Treatment in Adults With Major Depressive Disorder and Anxiety Symptoms
Study Start Date : November 2013
Actual Primary Completion Date : May 2014
Actual Study Completion Date : June 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Experimental: Brexpiprazole
Up to 3 mg/day, once daily dose, tablets, orally
Drug: Brexpiprazole
Treatment (6 weeks) - Up to 3mg/day, once daily dose, tablets, orally




Primary Outcome Measures :
  1. Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline, Week 6 ]
    The MADRS is utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale 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. The possible Total scores are from 0 to 60, with higher values indicating worse outcome.


Secondary Outcome Measures :
  1. Mean Change in Clinical Global Impression-Severity (CGI-S) Total Score [ Time Frame: Baseline, Week 6 ]
    The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 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.

  2. Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 6. [ Time Frame: Baseline, Week 6 ]
    The improvement of each participants condition was rated for each participant using the CGI-I. The study physician rated the participants total improvement whether or not it was due entirely to drug treatment. To perform this assessment, the study physician answered the following question: "Compared to his/her condition at baseline, how much has the participant changed?" Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared with the participants condition at Baseline prior to the first dose of study medication.

  3. Percentage of Participants With CGI-I Response Rate [ Time Frame: Week 1 to Week 6 ]
    The improvement of each participants condition was rated for each participant using the CGI-I. The study physician rated the participants total improvement whether or not it was due entirely to drug treatment. To perform this assessment, the study physician answered the following question: "Compared to his/her condition at baseline, how much has the participant changed?" Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared with the participants condition at Baseline prior to the first dose of study medication.

  4. Percentage of Participants With a MADRS Response [ Time Frame: Week 6 ]
    MADRS response rate, where response is defined as ≥ 50% reduction in respective total scores from Baseline to Week 6. The MADRS consists of 10 items, all rated on a 0 to 6 scale 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. The possible Total scores are from 0 to 60, higher values indicate worse outcome.

  5. Percentage of Participants With a MADRS Remission [ Time Frame: Week 6 ]
    MADRS remission rate, where remission is defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score from Baseline to Week 6. The MADRS consists of 10 items, all rated on a 0 to 6 scale 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. The possible Total scores are from 0 to 60, higher values indicate worse outcome.

  6. Mean Change From Baseline in Hamilton Depression Rating Scale (HAM-D17) Total Score [ Time Frame: Baseline, Week 6 ]
    The HAM-D17 was utilized as an assessment of a participants level of depression and was administered utilizing the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D). Detailed instructions for administration of this structured interview were provided in the SIGH-D. The HAM-D17 was administered at the following visits: screening, Baseline, and Week 6/ Early termination (ET). HAM-D17 is a 17-item questionnaire with a total score of 0 to 52 with higher scores indicating more depressive symptoms.

  7. Mean Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score [ Time Frame: Baseline, Week 6 ]
    The HAM-A was utilized for the evaluation of anxiety symptoms and was administered using the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A). Detailed instructions for administration of this structured interview were provided in the SIGH-A. The HAM-A was administered at the following visits: screening, Baseline, Weeks 1, 2, 3, 4, and 6/ET. HAM-A is a 14-item scale with each item is scored on a scale from 0 (not present) to 4 (very severe) with a total score of 0 to 56, with higher scores indicating severe anxiety symptoms.

  8. Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Score [ Time Frame: Baseline, Week 6 ]
    The SDS was a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. The SDS was a visual analogue scale that used spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the 3 domains. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0 = not at all to 10 = extremely. Scores of 5 and above were associated with significant functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).

  9. Mean Change From Baseline in Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score [ Time Frame: Baseline, Week 6 ]
    The MGH-CPFQ was a participant-rated scale designed to assess cognitive and executive dysfunction including symptoms of fatigue in mood and anxiety disorders. The MGH-CPFQ consisted of 7 items, each rated on a scale from 1 (greater than normal functioning) to 6 (poorer than normal functioning). The total score of the 7 items ranged from 7 to 42, with higher scores indicative of a worse outcome. The MGH-CPFQ was administered at the following visits: Baseline and Week 6/ET.

  10. Mean Change From Baseline in Kellner Symptom Questionnaire (KSQ) [ Time Frame: Baseline, Week 6 ]
    KSQ is a subject-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility and somatization. The questionnaire contains 92 items of which 68 items indicate symptoms and 24 items are antonyms of some of the symptoms that indicate well-being. The maximum score for each symptom subscale is 17, the well-being subscales 6 and for the total scale scores 23. A higher score indicates more distress than a lower score. The total subscale scores will be unevaluable if less than 19 of the 23 items are recorded. If 19 to 22 of the 23 items are recorded, the total subscale score is the mean of the recorded items multiplied by 23 and then rounded to the first decimal place. The total score will be unevaluable if less than 76 of the 92 items are recorded. If 76 to 91 of the 92 items and no less than 19 of the 23 items of each subscale are recorded, the total score will be the mean of the recorded items multiplied by 92 and then rounded to the first decimal place.

  11. Mean Change From Baseline in Go/No-Go Task for P-inhibition Failures [ Time Frame: Baseline, Week 6 ]
    Executive function and working memory were assessed for the Go/No-go Task using computer-based and paper-pencil neuropsychological instruments. These instruments focused on measuring impulse inhibition. The instrument was administered at the following visits: Baseline and Week 6/ET.

  12. Mean Change From Baseline in Go/No-Go Task for Mean Reaction Time [ Time Frame: Baseline, Week 6 ]
    Executive function and working memory were assessed for the Go/No-go Task using computer-based and paper-pencil neuropsychological instruments. These instruments focused on measuring impulse inhibition. The instrument was administered at the following visits: Baseline and Week 6/ET.

  13. Mean Change From Baseline in Delay Discounting Task - Monetary Choice Questionnaire (MCQ) Score [ Time Frame: Baseline, Week 6 ]
    Delay discounting was a participant-completed task is an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consists of 27 choices between immediate and delayed rewards. The participant chooses repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (for example, "would you prefer $27 today or $50 in 21 days?") The answers provide an estimate of the participant's discounting rate; higher discounting rates indicate greater impulsivity. A total score is not computed for all 27 questions.

  14. Mean Change From Baseline in Delay and Probability Discounting Task (DPDT) Scores [ Time Frame: Baseline, Week 6 ]
    The experiential discounting task (EDT) was a subject-completed computerized task designed to measure delay discounting, an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The participant chose between different amounts of money available at different delays or with different chances (probability to get the money). At the end of the session, one of the choices was selected at random, and the participant received whatever they chose in response of that question (immediate, delayed, or probabilistic amount). Formula for h-value: value = A / (1 + hO) p is probability of reward and O is odds against. The value of h indicates how the value of a reward and the probability of its occurrence decreases. The data are computerized and reflect delay discounting and impulsivity (higher discounting and higher probability discounting shows greater impulsivity). A total score is not computed for this task.

  15. Mean Change From Baseline to Week 6 in the Number of Impulsive Choices in the Delayed Reward Task (DRT) [ Time Frame: Baseline, Week 6 ]
    Delay discounting was a participant-completed task considered as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. During a training session, a single button with letter A or B appeared on the screen. The participant had to wait until the letter began to flash, and press the button only once. An amount of money was added to a counter and another single button appeared. During the test session, both buttons with letters A and B appeared on the screen. The participant had to choose one of the letters that remained; the other disappeared. The participant had to wait until the letter began to flash and then press the button again. An amount of money was added to the counter, and both letters appeared again. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). A total score was not calculated for this task.

  16. Mean Change From Baseline in Food Delay Discounting Task [ Time Frame: Baseline, Week 6 ]
    Delay discounting was a participant-completed task considered as an index of impulsive behavior. The participant chooses between a reward they could have today and another that they could get after a specified amount of time. The participant would not receive the rewards, but was asked to make decisions as though he or she were really going to receive them. AUC is defined as area under the concentration-time curve; AUC for food is presented below. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). To calculate the AUC, the "X-axis" is "days", "Y-axis" is "Food value", the actual area underneath the curve was calculated by summing the results for each delay and present value pair: x2 −x1[(y1 + y2)/2], where x1 and x2 are successive delays and y1 and y2 are the present values associated with those delays. The AUC can range from 1 (no discounting) to 0 (maximum discounting).

  17. Mean Change From Baseline in Money Delay Discounting Task [ Time Frame: Baseline, Week 6 ]
    Delay discounting was a participant-completed task considered as an index of impulsive behavior. The participant chose between a reward they could have today and another that they could get after a specified amount of time. The participant would not receive the rewards, but was asked to make decisions as though he or she were really going to receive them. AUC is defined as area under the concentration-time curve; AUC for money is presented below. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). To calculate the AUC, the "X-axis" is "days", "Y-axis" is "Money value", the actual area underneath the curve was calculated by summing the results for each delay and present value pair: x2 −x1[(y1 + y2)/2], where x1 and x2 are successive delays and y1 and y2 are the present values associated with those delays. The AUC can range from 1 (no discounting) to 0 (maximum discounting).

  18. Mean Change From Baseline in Barratt Impulsiveness Scale 11-item (BIS-11) Total Score [ Time Frame: Baseline, Week 6 ]
    The BIS-11 was a participant-rated scale designed to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provided information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, non-planning impulsiveness, and attentional impulsiveness). The total score ranged from 30 to 120, with higher scores indicating impulsive personality traits. The BIS-11 was administered at the following visits: Baseline and Week 6/ET.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Main Inclusion Criteria:

  • Have a diagnosis of a single or recurrent, nonpsychotic episode of MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and confirmed by both the Mini International Neuropsychiatric Interview (M.I.N.I.) and an adequate clinical psychiatric evaluation.
  • Have a treatment history of an inadequate ADT response to at least 1 ADT (but not > 3) for the current episode.
  • Have received a single, trial-approved, SSRI or SNRI at an adequate dose for

    ≥ 6 weeks prior to screening.

  • Are 18 to 65 years old at the time of consent (inclusive, and outpatients only).
  • Have a Hamilton Depression Rating Scale (HAM-D)-17-item Total Score ≥ 18 at screening and baseline.
  • Have a Hamilton Anxiety Rating Scale (HAM-A) Total Score ≥ 20 at screening and baseline.

Main Exclusion Criteria:

Subjects with any of the following current Axis I DSM-IV-TR diagnoses:

  • delirium
  • dementia
  • amnestic
  • other cognitive disorders
  • schizophrenia
  • schizoaffective disorder
  • other psychotic disorders
  • bipolar I disorder,
  • bipolar II disorder
  • bipolar disorder not otherwise specified (NOS)
  • eating disorders
  • anorexia nervosa
  • bulimia
  • obsessive compulsive disorder
  • post-traumatic stress disorder

Subjects with any of the following current Axis II DSM-IV-TR diagnoses:

  • borderline, antisocial
  • paranoid
  • schizoid
  • schizotypal
  • histrionic personality disorders
  • mental retardation.

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): NCT02013531


Locations
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United States, Arizona
Tuscon, Arizona, United States, 85712
United States, California
Garden Grove, California, United States, 92845
Oceanside, California, United States, 92056
Temecula, California, United States, 92591
United States, Florida
Gainesville, Florida, United States, 32607
Jacksonville, Florida, United States, 32256
Miami, Florida, United States, 33145
United States, Georgia
Atlanta, Georgia, United States, 30308
United States, Indiana
Lafayette, Indiana, United States, 47905
United States, Maryland
Baltimore, Maryland, United States, 21208
United States, Massachusetts
Boston, Massachusetts, United States, 02131
Haverhill, Massachusetts, United States, 01830
United States, Michigan
Rochester Hills, Michigan, United States, 48307
United States, New York
New York, New York, United States, 10168
Staten Island, New York, United States, 10305
United States, Oregon
Salem, Oregon, United States, 97301
United States, Pennsylvania
Allentown, Pennsylvania, United States, 18104
United States, Texas
Arlington, Texas, United States, 76012
Austin, Texas, United States, 78731
United States, Vermont
Woodstock, Vermont, United States, 05091
United States, Virginia
Richmond, Virginia, United States, 23230
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Otsuka Pharmaceutical Co., Ltd.
Investigators
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Study Director: Junichi Hashimoto, PhD Otsuka Pharmaceutical Co., Ltd Japan (OPCJ)

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT02013531     History of Changes
Other Study ID Numbers: 331-13-002
First Posted: December 17, 2013    Key Record Dates
Results First Posted: March 29, 2016
Last Update Posted: March 29, 2016
Last Verified: February 2016

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
schizophrenia
Major depressive disorder
Anxiety Symptoms
Mental Disorders
Psychotic Disorders
emotional withdrawal
antipsychotic

Additional relevant MeSH terms:
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Depressive Disorder
Depression
Depressive Disorder, Major
Disease
Anxiety Disorders
Pathologic Processes
Mental Disorders
Mood Disorders
Behavioral Symptoms
Brexpiprazole
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents