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

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ClinicalTrials.gov Identifier: NCT02012218
Recruitment Status : Completed
First Posted : December 16, 2013
Results First Posted : October 8, 2015
Last Update Posted : December 29, 2015
Sponsor:
Collaborator:
Otsuka Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Major Depressive Disorder (MDD)
Interventions Drug: ADT
Drug: Brexpiprazole
Enrollment 61
Recruitment Details This trial was conducted in 61 participants in 28 trial sites, all of which were located in the United States.
Pre-assignment Details The trial consisted of a continuous 6-week open-label treatment period including an initial 2-week titration period with a 30-day (+2 days) follow-up period.
Arm/Group Title Group 1A Group 1B Group 2 Group 3 Group 4
Hide Arm/Group Description Participants who had received a prescribed number of tablets of aripiprazole (baseline/primary antidepressant therapy [ADT]) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of quetiapine IR (immediate release) or XR (extended release) (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of any Selective Serotonin Reuptake Inhibitors (SSRI), any Serotonin-norepinephrine Reuptake Inhibitors (SNRI), any tricyclic antidepressant, or Oleptro (trazodone hydrochloride) IR or XR (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of bupropion (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of stimulants such as modafinil, methylphenidate, or psychostimulant (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.
Period Title: Overall Study
Started 12 11 13 19 6
Completed 8 10 11 17 5
Not Completed 4 1 2 2 1
Reason Not Completed
Withdrawal by Subject             1             0             1             1             1
Adverse Event             1             0             0             1             0
Lost to Follow-up             0             1             1             0             0
Protocol Specified             1             0             0             0             0
Protocol Deviation             1             0             0             0             0
Arm/Group Title Group 1A Group 1B Group 2 Group 3 Group 4 Total
Hide Arm/Group Description Participants who had received a prescribed number of tablets of aripiprazole (baseline/primary antidepressant therapy [ADT]) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of quetiapine IR (immediate release) or XR (extended release) (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of any Selective Serotonin Reuptake Inhibitors (SSRI), any Serotonin-norepinephrine Reuptake Inhibitors (SNRI), any tricyclic antidepressant, or Oleptro (trazodone hydrochloride) IR or XR (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of bupropion (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of stimulants such as modafinil, methylphenidate, or psychostimulant (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Total of all reporting groups
Overall Number of Baseline Participants 12 11 13 19 6 61
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 11 participants 13 participants 19 participants 6 participants 61 participants
50.2  (8.13) 41.8  (13.57) 48.5  (12.20) 44.1  (13.64) 41.7  (13.59) 45.6  (12.44)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 13 participants 19 participants 6 participants 61 participants
Female
7
  58.3%
7
  63.6%
11
  84.6%
15
  78.9%
3
  50.0%
43
  70.5%
Male
5
  41.7%
4
  36.4%
2
  15.4%
4
  21.1%
3
  50.0%
18
  29.5%
1.Primary Outcome
Title Mean Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Hide Description 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.
Time Frame Baseline and Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid post-baseline efficacy assessment.
Arm/Group Title Group 1A Group 1B Group 2 Group 3 Group 4
Hide Arm/Group Description:
Participants who had received a prescribed number of tablets of aripiprazole (baseline/primary antidepressant therapy [ADT]) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.
Participants who had received a prescribed number of tablets of quetiapine IR (immediate release) or XR (extended release) (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.
Participants who had received a prescribed number of tablets of any Selective Serotonin Reuptake Inhibitors (SSRI), any Serotonin-norepinephrine Reuptake Inhibitors (SNRI), any tricyclic antidepressant, or Oleptro (trazodone hydrochloride) IR or XR (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.
Participants who had received a prescribed number of tablets of bupropion (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.
Participants who had received a prescribed number of tablets of stimulants such as modafinil, methylphenidate, or psychostimulant (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.
Overall Number of Participants Analyzed 12 10 12 19 6
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-12.8  (2.26) -18.4  (2.10) -19.5  (1.99) -19.2  (1.59) -16.8  (2.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1A, Group 1B, Group 2, Group 3, Group 4
Comments The null hypothesis of zero in mean change from baseline in MADRS total score at Week 6 was tested for each treatment group at significance level of 0.05 (2-sided).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-values were calculated according to testing a null hypothesis of zero mean change.
Method Mixed Models Analysis
Comments This analysis was conducted using a mixed model repeated measures analysis on observed case data.
Time Frame Adverse events were reported from the signing of the informed consent until the end of trial with a safety follow-up of 30 (+2 ) days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group 1A Group 1B Group 2 Group 3 Group 4
Hide Arm/Group Description Participants who had received a prescribed number of tablets of aripiprazole (baseline/primary antidepressant therapy [ADT]) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of quetiapine IR (immediate release) or XR (extended release) (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of any Selective Serotonin Reuptake Inhibitors (SSRI), any Serotonin-norepinephrine Reuptake Inhibitors (SNRI), any tricyclic antidepressant, or Oleptro (trazodone hydrochloride) IR or XR (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of bupropion (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period. Participants who had received a prescribed number of tablets of stimulants such as modafinil, methylphenidate, or psychostimulant (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.
All-Cause Mortality
Group 1A Group 1B Group 2 Group 3 Group 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Group 1A Group 1B Group 2 Group 3 Group 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   1/11 (9.09%)   0/13 (0.00%)   0/19 (0.00%)   0/6 (0.00%) 
Musculoskeletal and connective tissue disorders           
Rhabdomyolysis * 1  0/12 (0.00%)  1/11 (9.09%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1A Group 1B Group 2 Group 3 Group 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/12 (58.33%)   8/11 (72.73%)   6/13 (46.15%)   15/19 (78.95%)   5/6 (83.33%) 
Cardiac disorders           
Atrioventricular block first degree * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  0/19 (0.00%)  1/6 (16.67%) 
Eye disorders           
Vision blurred * 1  1/12 (8.33%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Gastrointestinal disorders           
Dry mouth * 1  2/12 (16.67%)  0/11 (0.00%)  1/13 (7.69%)  2/19 (10.53%)  0/6 (0.00%) 
Diarrhoea * 1  0/12 (0.00%)  0/11 (0.00%)  1/13 (7.69%)  3/19 (15.79%)  0/6 (0.00%) 
Abdominal distension * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  0/19 (0.00%)  1/6 (16.67%) 
Constipation * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Nausea * 1  0/12 (0.00%)  0/11 (0.00%)  1/13 (7.69%)  0/19 (0.00%)  0/6 (0.00%) 
Oesophagitis * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
General disorders           
Fatigue * 1  1/12 (8.33%)  0/11 (0.00%)  2/13 (15.38%)  3/19 (15.79%)  3/6 (50.00%) 
Infections and infestations           
Upper respiratory tract infection * 1  1/12 (8.33%)  1/11 (9.09%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Nasopharyngitis * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  0/19 (0.00%)  1/6 (16.67%) 
Sinusitis * 1  0/12 (0.00%)  1/11 (9.09%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Viral infection * 1  0/12 (0.00%)  1/11 (9.09%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications           
Fall * 1  0/12 (0.00%)  1/11 (9.09%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Head injury * 1  0/12 (0.00%)  1/11 (9.09%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Ligament sprain * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Investigations           
Weight increased * 1  0/12 (0.00%)  1/11 (9.09%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Weight decreased * 1  0/12 (0.00%)  0/11 (0.00%)  1/13 (7.69%)  0/19 (0.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders           
Increased appetite * 1  1/12 (8.33%)  1/11 (9.09%)  1/13 (7.69%)  2/19 (10.53%)  0/6 (0.00%) 
Dyslipidaemia * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Food craving * 1  0/12 (0.00%)  0/11 (0.00%)  1/13 (7.69%)  0/19 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders           
Back pain * 1  1/12 (8.33%)  0/11 (0.00%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Muscle rigidity * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Musculoskeletal chest pain * 1  1/12 (8.33%)  0/11 (0.00%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Tendonitis * 1  0/12 (0.00%)  1/11 (9.09%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Nervous system disorders           
Akathisia * 1  2/12 (16.67%)  0/11 (0.00%)  0/13 (0.00%)  3/19 (15.79%)  0/6 (0.00%) 
Headache * 1  1/12 (8.33%)  1/11 (9.09%)  1/13 (7.69%)  1/19 (5.26%)  1/6 (16.67%) 
Somnolence * 1  0/12 (0.00%)  0/11 (0.00%)  1/13 (7.69%)  2/19 (10.53%)  1/6 (16.67%) 
Disturbance in attention * 1  0/12 (0.00%)  0/11 (0.00%)  2/13 (15.38%)  0/19 (0.00%)  0/6 (0.00%) 
Poor quality sleep * 1  0/12 (0.00%)  1/11 (9.09%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Sedation * 1  0/12 (0.00%)  0/11 (0.00%)  1/13 (7.69%)  0/19 (0.00%)  1/6 (16.67%) 
Tension headache * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  2/19 (10.53%)  0/6 (0.00%) 
Aphasia * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Cognitive disorder * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Dizziness * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Extrapyramidal disorder * 1  1/12 (8.33%)  0/11 (0.00%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Glabellar reflex abnormal * 1  0/12 (0.00%)  0/11 (0.00%)  1/13 (7.69%)  0/19 (0.00%)  0/6 (0.00%) 
Lethargy * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Paraesthesia * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Memory impairment * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  0/19 (0.00%)  1/6 (16.67%) 
Psychiatric disorders           
Restlessness * 1  0/12 (0.00%)  1/11 (9.09%)  2/13 (15.38%)  2/19 (10.53%)  0/6 (0.00%) 
Insomnia * 1  0/12 (0.00%)  1/11 (9.09%)  2/13 (15.38%)  1/19 (5.26%)  0/6 (0.00%) 
Anxiety * 1  1/12 (8.33%)  1/11 (9.09%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Initial insomnia * 1  0/12 (0.00%)  1/11 (9.09%)  0/13 (0.00%)  0/19 (0.00%)  1/6 (16.67%) 
Agitation * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Depressive symptom * 1  0/12 (0.00%)  0/11 (0.00%)  1/13 (7.69%)  0/19 (0.00%)  0/6 (0.00%) 
Disinhibition * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Distractibility * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Middle insomnia * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Renal and urinary disorders           
Urinary retention * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Reproductive system and breast disorders           
Menstrual disorder * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Epistaxis * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Increased upper airway secretion * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Nasal congestion * 1  1/12 (8.33%)  0/11 (0.00%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Yawning * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders           
Acne * 1  0/12 (0.00%)  0/11 (0.00%)  0/13 (0.00%)  1/19 (5.26%)  0/6 (0.00%) 
Dermatitis contact * 1  0/12 (0.00%)  1/11 (9.09%)  0/13 (0.00%)  0/19 (0.00%)  0/6 (0.00%) 
Intertrigo * 1  0/12 (0.00%)  0/11 (0.00%)  1/13 (7.69%)  0/19 (0.00%)  0/6 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Global Medical Affairs
Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.
Phone: 800 562-3974
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT02012218     History of Changes
Other Study ID Numbers: 331-13-001
First Submitted: December 4, 2013
First Posted: December 16, 2013
Results First Submitted: September 4, 2015
Results First Posted: October 8, 2015
Last Update Posted: December 29, 2015