Clinical trial NCT02012218: Brexpiprazole as Adjunctive Therapy With Major Depressive Disorder and an Inadequate Response to Previous Adjunctive Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder (MDD)
Keywords: Major Depressive Disorder, Depression
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Otsuka Pharmaceutical Co., Ltd.
First posted: 2013-12-16
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mean Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline and Week 6
Secondary outcomes:
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: Collaborative NeuroScience Network, Inc.
state: California
city: Temecula
country: United States
facility: Viking Clinical Research, Ltd.
state: California
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions Pharmacology
state: Florida
city: Smyrna
country: United States
facility: Carman Research
state: Georgia
city: Indianapolis
country: United States
facility: Goldpoint Clinical Research
state: Indiana
city: Lafayette
country: United States
facility: Alpine Clinic
state: Indiana
city: Baltimore
country: United States
facility: Pharmasite Research
state: Maryland
city: Boston
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: Weymouth
country: United States
facility: Coastal Research Associates, Inc.
state: Massachusetts
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine
state: Michigan
city: St. Louis
country: United States
facility: St. Louis Clinical Trials
state: Missouri
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
city: Staten Island
country: United States
facility: Behavioral Medical Research of Staten Island
state: New York
city: Raleigh
country: United States
facility: Richard H. Weisler, MD, PA
state: North Carolina
city: Dayton
country: United States
facility: Midwest Clinical Research Center MCRC
state: Ohio
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Portland
country: United States
facility: Oregon Center for Clinical Investigations, Inc.
state: Oregon
city: Salem
country: United States
facility: Oregon Center for Clinical Investigations, Inc.
state: Oregon
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Lincoln
country: United States
facility: Lincoln Research, LLC
state: Rhode Island
city: Memphis
country: United States
facility: Research Strategies of Memphis, LLC
state: Tennessee
city: Dallas
country: United States
facility: Future Search Trials of Dallas, LP
state: Texas
city: Woodstock
country: United States
facility: NeuropsychiatricAssociates
state: Vermont
city: Spokane
country: United States
facility: Frontier Institute
state: Washington
Study officials:
affiliation: Otsuka Pharmaceutical Co., Ltd Japan (OPCJ)
name: Junichi Hashimoto, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.