Brexpiprazole for Bipolar Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03427892
Recruitment Status : Completed
First Posted : February 9, 2018
Last Update Posted : April 23, 2018
Otsuka America Pharmaceutical
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

Brief Summary:

The investigators will conduct an 8-week, non-randomized, open-label study of brexpiprazole in 20 persons with bipolar I or II disorder, depressed mood state. Primary aim will be to assess if brexpiprazole is associated with a reduction in depressive symptom severity using the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary aims will include an assessment of the following in patients with bipolar disorder taking brexpiprazole: manic symptoms, cognition, safety and tolerability of brexpiprazole, and quality of life.

Subjects will be discontinued from the study if any of the following conditions occurs: change in diagnosis to other than bipolar I or II disorder, development of active suicidal or homicidal ideation with plan and intent, worsening of mood symptoms, that in the opinion of the investigators requires discontinuation, pregnancy, development of severe life-threatening medical condition, involuntary psychiatric hospitalization or incarceration.

Condition or disease Intervention/treatment Phase
Bipolar Depression Drug: Brexpiprazole Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Brexpiprazole for Bipolar Depression
Actual Study Start Date : March 1, 2017
Actual Primary Completion Date : March 15, 2018
Actual Study Completion Date : March 15, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Brexpiprazole
Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.
Drug: Brexpiprazole
Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.
Other Name: Rexulti

Primary Outcome Measures :
  1. The Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 8 weeks ]
    The Montgomery-Asberg Depression Rating Scale is used to assess depressive symptom severity. There are 10 items and each item is rated from 0 to 6 (increasing severity) based on the assessment of symptoms within the past 7 days. Scoring is assisted by descriptive anchors that serve as useful guides at 0,2,4, 8. Odd numbers (1,3,5) between the descriptive anchors are also meant to be scored. Highest possible MADRS score is 60. Lowest possible MADRS score is 0. MADRS is scored by taking the sum of the scores for each item. A higher score is indicative of more acute depressive symptoms.

Secondary Outcome Measures :
  1. Young Mania Rating Scale (YMRS) [ Time Frame: 8 weeks ]
    Young Mania Rating Scale is an observer-rated measure of mania symptomatology. It has 11 items and each items has 5 defined anchor points with increasing severity that describe the symptom characteristics. YMRS is scored by taking sum of the scores for the 11 items. A higher score indicative of more acute manic symptoms. Seven of the items are scored between 0 and 4. Four items allow for schoring between anchor points (ranging 1 to 8). Maximum score is 60 and minimum score is 0.

  2. Rey Auditoy Verbal Learning Test [ Time Frame: 8 weeks ]
    RAVLT evaluates a wide diversity of functions, including short-term auditory-verbal memory, and retention of information. A list of 15 words are read out loud in 5 trials and participants are asked to recall the words read after each trial. Each trial recall is scored from 0-15 (0 minimum-15 maximum, 1 point per correctly recalled word). Total Score is sum of scores from trial 1-5. 3 more trials of word recall are done and scored in the same way. Then, participants are asked to identify words from an earlier list of words. The number of correct words recalled is the Hits score (0 min. score - 15 max. score, 1 point per word) and sum of incorrectly recalled words are the false positive error score (score range: 0-35). A discrimination score is derived by subtracting False Positive Error from Hits (score range -35 to 15). Higher score denotes better recall.

  3. Stroop task [ Time Frame: 8 weeks ]
    The Stroop task evaluates attention, speed, and accuracy of thinking

  4. Trail Making Test (TMT) [ Time Frame: 8 weeks ]
    The Trail Making Test measures attention, speed and accuracy

  5. Systematic Assessment For Treatment Emergent Events [ Time Frame: 8 weeks ]
    The Systematic Assessment for Treatment Emergent Effects (SAFTEE) is a side effect symptom scale.

  6. Columbia Suicide Severity Rating Scale [ Time Frame: 8 weeks ]
    The Columbia Suicide Severity Rating Scale (C-SSRS) is a structured interview and rating scale used to measure suicidal thoughts and behaviors.

  7. Abnormal Involuntary Movement Scale [ Time Frame: 8 weeks ]
    The Abnormal Involuntary Movement Scale (AIMS) is an assessment of movements to determine any long-term drug induced movement disorders.There are 10 items on the scale with scores ranging from 0-4 (0 None/Normal, 1 minimal, 2 mild, 3 moderate,4 severe). 4 items assess facial and oral movements, 2 items measure extremity movements, 1 item measures trunk movements, and 3 items measure global judgments regarding symptoms assessed. A total score is the sum of scores for items assessing facial and oral movements, extremity movements, and trunk movement (scores ranging from 0-28), with 0 being the lowest score, and 28 being the highest score. A higher score is indicative of a higher severity in symptomatology.

  8. Barnes Akathisia Scale [ Time Frame: 8 weeks ]
    The Barnes Akathisia Scale (BAS) is an assessment of movements to determine any short-term drug-induced movement disorders. There are 5 items.Items 1-3 are rated from a scale of 0-3 with 0 indicating the least severity, and 3 indicating the highest severity of symptoms. Item 4 is a global assessment of symptoms assessed and the severity is assessed on a scale of 0-5, with 0 indication least severity and 5 indicating the most severity.The total score is the sum of all the item scores (scores ranging from 0-14).

  9. Simpson Angus Scale [ Time Frame: 8 weeks ]
    The Simpson Angus Scale (SAS) is an assessment of movements that also determines any short-term drug induced movement disorders. There are 10 items with each items scored on a scale of 0-4, and indicates the severity of symptoms assessed (0=least severe, 4=most severe). The total score is the sum of all 10 items.

  10. Quality of Life in Bipolar Disorder (QOLBD) [ Time Frame: 8 weeks ]
    The Quality Of Life in Bipolar Disorder measures the 12 domains of quality of life in patients with bipolar disorder.

Other Outcome Measures:
  1. high sensitivity C-Reactive Protein (hs-CRP) [ Time Frame: 8 weeks ]
    high sensitivity C-Reactive Protein values will be used to measure inflammation

  2. Pearson's or Spearman's correlation coefficients [ Time Frame: 8 weeks ]
    Correlations between outcome measures (e.g. depressive symptoms and cognition, depressive symptoms and inflammation)

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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

Inclusion Criteria:

  • Outpatient men and women ages 18-65
  • Bipolar I or II disorders, currently depressed mood state based on a SCID for DSM-5; Mixed features in DSM-5 are allowed, but those with a Young Mania Rating Scale score ≥ 15 will be excluded
  • Baseline MADRS score ≥ 20

Exclusion Criteria:

  • Mood disorders other than bipolar I or II disorders (e.g., bipolar NOS, or cyclothymic disorders, schizophrenia, schizoaffective disorder, or unipolar depression based on the SCID), other disorders, e.g. anxiety disorders, will be allowed
  • Current (last 14 days) treatment with an antipsychotic or antidepressant
  • History of neuroleptic malignant syndrome or tardive dyskinesia
  • Prior history of brexpiprazole use
  • Vulnerable populations (e.g., pregnant, nursing, cognitively impaired, incarcerated)
  • High risk for suicide defined as > 1 attempt in past 12 months that required medical attention, any attempt in the past 3 months or current suicidal ideation with plan and intent such that outpatient care is precluded
  • Severe or life-threatening medical condition, or laboratory or physical examination findings consistent with serious medical illness (e.g., dangerously abnormal electrolytes)
  • Moderate or severe hepatic or renal impairment based on medical history and laboratory analyses
  • Taking moderate or strong induces or inhibitors of CYP2D6 or CYP3A4

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 identifier (NCT number): NCT03427892

United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Otsuka America Pharmaceutical
Principal Investigator: Sherwood Brown, M.D., Ph.D. UT Southwestern Medical Center

Responsible Party: University of Texas Southwestern Medical Center Identifier: NCT03427892     History of Changes
Other Study ID Numbers: 102016-048
First Posted: February 9, 2018    Key Record Dates
Last Update Posted: April 23, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Texas Southwestern Medical Center:

Additional relevant MeSH terms:
Depressive Disorder
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents