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

Major Depressive Disorder (MDD) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02012218
• Other study ID #: 331-13-001
• Status: Completed
• Phase: Phase 3
• First received: December 4, 2013
• Last updated: November 30, 2015
• Start date: November 2013
• Est. completion date: October 2014

Study information

• Verified date: November 2015
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder (MDD)

Intervention

Drug:
• ADT

• Brexpiprazole

Locations

Country	Name	City	State
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	Pharmasite Research	Baltimore	Maryland
United States	Boston Clinical Trials	Boston	Massachusetts
United States	Center for Emotional Fitness	Cherry Hill	New Jersey
United States	Future Search Trials of Dallas, LP	Dallas	Texas
United States	Midwest Clinical Research Center MCRC	Dayton	Ohio
United States	Collaborative NeuroScience Network, Inc.	Garden Grove	California
United States	Goldpoint Clinical Research	Indianapolis	Indiana
United States	Alpine Clinic	Lafayette	Indiana
United States	Lincoln Research, LLC	Lincoln	Rhode Island
United States	Research Strategies of Memphis, LLC	Memphis	Tennessee
United States	Cutting Edge Research Group	Oklahoma City	Oklahoma
United States	Clinical Neuroscience Solutions Pharmacology	Orlando	Florida
United States	Oregon Center for Clinical Investigations, Inc.	Portland	Oregon
United States	Richard H. Weisler, MD, PA	Raleigh	North Carolina
United States	Rochester Center for Behavioral Medicine	Rochester Hills	Michigan
United States	Oregon Center for Clinical Investigations, Inc.	Salem	Oregon
United States	Carman Research	Smyrna	Georgia
United States	Frontier Institute	Spokane	Washington
United States	St. Louis Clinical Trials	St. Louis	Missouri
United States	Behavioral Medical Research of Staten Island	Staten Island	New York
United States	Viking Clinical Research, Ltd.	Temecula	California
United States	Coastal Research Associates, Inc.	Weymouth	Massachusetts
United States	NeuropsychiatricAssociates	Woodstock	Vermont

Sponsors (2)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.	Otsuka Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No