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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder (MDD)
• Intervention / Treatment: Drug: ADT; Drug: Brexpiprazole

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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
• 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

Exclusion Criteria:

• 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
• 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:

  1. Platelets ≤ 75,000/mm3
  2. Hemoglobin ≤ 9 g/dL
  3. Neutrophils, absolute ≤ 1000/mm3
  4. AST > 2 × ULN
  5. ALT > 2 × ULN
  6. CPK > 3 × ULN, unless discussed with and approved by the medical monitor
  7. Creatinine ≥ 2 mg/dL
  8. HbA1c ≥ 7.0%
  9. Abnormal free T4 (Note: Free T4 is measured only if result for TSH is abnormal.)
  10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADT and Brexpiprazole	Drug: ADT; Drug: Brexpiprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Week 6

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: Otsuka Pharmaceutical Co., Ltd.

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: December 4, 2013
• First Submitted That Met QC Criteria: December 10, 2013
• First Posted (Estimate): December 16, 2013

Study Record Updates

• Last Update Posted (Estimate): December 29, 2015
• Last Update Submitted That Met QC Criteria: November 30, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Major Depressive Disorder, Depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Dopamine Agonists; Dopamine Agents; Brexpiprazole
• Other Study ID Numbers: 331-13-001