| Trial | Outcome |
|---|
| NCT00797966 (14) [back to overview] | Change From End of Phase A (Week 8 Visit) in Mean CGI-S Score for Every Study Week Visit in Phase B Other Than the Week 14 Visit. |
| NCT00797966 (14) [back to overview] | Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Q-LES-Q-SF Item 16 Score (Overall Life Satisfaction). |
| NCT00797966 (14) [back to overview] | Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Q-LES-Q-SF Item 15 Score (Satisfaction With Medication). |
| NCT00797966 (14) [back to overview] | Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. |
| NCT00797966 (14) [back to overview] | Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Depression Rating Scale (HAM-D17) Score. |
| NCT00797966 (14) [back to overview] | Clinical Global Impression-Improvement Scale (CGI-I) Score at Each Study Week Visit in Phase B. |
| NCT00797966 (14) [back to overview] | Percentage of Participants With CGI-I Response From End of Phase A (Week 8 Visit). |
| NCT00797966 (14) [back to overview] | Percentage of Participants With MADRS Response From End of Phase A (Week 8 Visit). |
| NCT00797966 (14) [back to overview] | Percentage of Participants With MADRS Remission From End of Phase A (Week 8 Visit). |
| NCT00797966 (14) [back to overview] | Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score. |
| NCT00797966 (14) [back to overview] | Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Score (the Mean of 3 Individual Item Scores). |
| NCT00797966 (14) [back to overview] | Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. |
| NCT00797966 (14) [back to overview] | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than the Week 14 Visit. |
| NCT00797966 (14) [back to overview] | Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Quality of Life, Enjoyment, and Satisfaction Questionnaire - Short Form (QLES-Q-SF) Subscale Score - the Overall General Subscore (Sum of First 14 Items). |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in the Rapid Visual Information Processing (RVP) A Prime Test Score as Measured by CANTAB to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in SST Median Reaction Time Score on Go Trials as Measured by CANTAB to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in Sleep Improvement Measured by ISI for Item 2 Score (Difficulty Staying Asleep) to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in Sleep Improvement Measured by Insomnia Severity Index (ISI) Total Score to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in RVP Total False Alarms Score as Measured by CANTAB to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in the Stop Signal Task (SST) Stop Signal Reaction Time (SSRT) Score as Measured by CANTAB to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in the SWM Within Errors 4-8 Boxes Test Score as Measured by CANTAB to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) Total Score to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score to Each Timepoint in Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in CAARS-S:SV Inattentive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B |
| NCT01074294 (33) [back to overview] | Mean Change From Baseline (End of Phase A) in the CAARS-O:SV ADHD Symptoms Total Score (18 Items) to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in CAARS-S:SV ADHD Index Score (12 Items) to Each Timepoint in Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in WRAADDS Attention + Organization Subscale Score to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in CAARS-O:SV Inattentive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in CAARS-O:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Symptoms Total Score (18 Items) to Each Time Point in Phase B Other Than Week 11 |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Index Score (12 Items) to Each Time Point in Phase B |
| NCT01074294 (33) [back to overview] | Change From End of Phase A (Week 5 Visit) to End of Phase B (Week 11 Visit) in WRAADDS Hyperactivity + Impulsivity Subscale Score to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in WRAADDS Temper + Mood Lability + Emotional Over-reactivity Subscale Score to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in CAARS-S:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in the SST Proportion of Successful Stops Score as Measured by CANTAB to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in the Spatial Working Memory (SWM) Between Errors 4-8 Boxes Test Score as Measured by Cambridge Neuropsychological Test Automated Battery (CANTAB) to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in the RVP Median Response Latency Score as Measured by CANTAB to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in the SWM Strategy 6-8 Boxes Test Score as Measured by CANTAB to End of Phase B |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) to Weeks 7 and 9 in ISI Total Score |
| NCT01074294 (33) [back to overview] | Change From Baseline (End of Phase A) in Conners' Adult ADHD Rating Scale-Self-Report: Screening Version (CAARS-S:SV) ADHD Symptoms Total Score (18 Items) to Each Timepoint in Phase B |
| NCT01074294 (33) [back to overview] | Percentage of Participants With CGI-I Response Rate in Phase B |
| NCT01074294 (33) [back to overview] | Mean CGI-I Score at Each Timepoint in Phase B |
| NCT01074294 (33) [back to overview] | Percentage of Participants With CAARS-O:SV ADHD Symptoms Remission Rate in Phase B |
| NCT01074294 (33) [back to overview] | Percentage of Participants With CAARS-O:SV ADHD Symptoms Response Rate in Phase B |
| NCT01074294 (33) [back to overview] | Percentage of Participants With CAARS-S:SV ADHD Symptoms Remission Rate in Phase B |
| NCT01074294 (33) [back to overview] | Percentage of Participants With CAARS-S:SV ADHD Symptoms Response Rate in Phase B |
| NCT01074294 (33) [back to overview] | Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B |
| NCT01396421 (16) [back to overview] | Clinical Global Impression- Improvement Scale (CGI-I) Score at Week 6 |
| NCT01396421 (16) [back to overview] | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. |
| NCT01396421 (16) [back to overview] | Mean Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. |
| NCT01396421 (16) [back to overview] | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score |
| NCT01396421 (16) [back to overview] | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score |
| NCT01396421 (16) [back to overview] | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score |
| NCT01396421 (16) [back to overview] | Mean Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) |
| NCT01396421 (16) [back to overview] | Response Rate at Week 6 |
| NCT01396421 (16) [back to overview] | Mean Change From Baseline to Week 6 Positive and Negative Syndrome Scale (PANSS) Total Score. |
| NCT01396421 (16) [back to overview] | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. |
| NCT01396421 (16) [back to overview] | Change From Baseline to Week 6 in PANSS Marder Anxiety Depression Score |
| NCT01396421 (16) [back to overview] | Change From Baseline to Week 6 in PANSS Marder Disorganised Thought Score |
| NCT01396421 (16) [back to overview] | Change From Baseline to Week 6 in PANSS Marder Factor Score - Negative Symptoms Score |
| NCT01396421 (16) [back to overview] | Change From Baseline to Week 6 in PANSS Marder Factor Score - Positive Symptoms Score |
| NCT01396421 (16) [back to overview] | Change From Baseline to Week 6 in PANSS Marder Uncontrolled Hostility/Excitement Score |
| NCT01396421 (16) [back to overview] | Discontinuation Rate for Lack of Efficacy at Week 6 |
| NCT01668797 (29) [back to overview] | Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C. |
| NCT01668797 (29) [back to overview] | Percentage of Participants Who Discontinued Due to All Causes |
| NCT01668797 (29) [back to overview] | Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance Phase |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PSP Scale Score - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in Personal and Social Performance (PSP) Scale Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PEC Score - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Mean Change From Baseline in GAF Scale Score - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis |
| NCT01668797 (29) [back to overview] | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis |
| NCT01668797 (29) [back to overview] | Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis |
| NCT01670279 (10) [back to overview] | Mean Change From Baseline to Study Completion in Simpson-Angus Scale (SAS) Total Score |
| NCT01670279 (10) [back to overview] | Number of AEs Reported. |
| NCT01670279 (10) [back to overview] | Incidence of Physical Examination Evaluation of Potential Clinical Significance |
| NCT01670279 (10) [back to overview] | Number of Participants Who Tolerated Brexpiprazole |
| NCT01670279 (10) [back to overview] | Change From Baseline to Study Completion in C-SSRS Score. |
| NCT01670279 (10) [back to overview] | Incidence of ECG Evaluations of Potential Clinical Significance |
| NCT01670279 (10) [back to overview] | Incidence of Laboratory Values of Potential Clinical Significance |
| NCT01670279 (10) [back to overview] | Incidence of Vital Signs of Potential Clinical Significance |
| NCT01670279 (10) [back to overview] | Mean Change From Baseline to Study Completion in Abnormal Involuntary Movement Scale (AIMS) Rating Score. |
| NCT01670279 (10) [back to overview] | Mean Change From Baseline to Study Completion in Barnes Akathisia Global Score |
| NCT01727726 (9) [back to overview] | CGI-I Response Rate |
| NCT01727726 (9) [back to overview] | Sheehan Disability Scale (SDS) Individual Item Scores. |
| NCT01727726 (9) [back to overview] | MADRS Response at Week 6 |
| NCT01727726 (9) [back to overview] | Montgomery Asberg Depression Rating Scale (MADRS) |
| NCT01727726 (9) [back to overview] | Number of Participants With MADRS |
| NCT01727726 (9) [back to overview] | Sheehan Disability Scale (SDS) |
| NCT01727726 (9) [back to overview] | Change From End of Phase A in MADRS Total Score for Trial Week 2 and Week 4. |
| NCT01727726 (9) [back to overview] | Clinical Global Impression Score |
| NCT01727726 (9) [back to overview] | Number of Participants With Adverse Events |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PANSS Positive Subscale Score |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PANSS Negative Subscale Score |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PANSS Total Score |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PSP Total Score |
| NCT01810380 (18) [back to overview] | Discontinuation Due to Lack of Efficacy During the Study |
| NCT01810380 (18) [back to overview] | PSP Domain D: Disturbing and Aggressive Behaviours at Week 6 |
| NCT01810380 (18) [back to overview] | PSP Functional Remission Rate at Week 6 |
| NCT01810380 (18) [back to overview] | PSP Functional Response Rate at Week 6 |
| NCT01810380 (18) [back to overview] | Response Rate at Week 6 |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thoughts |
| NCT01810380 (18) [back to overview] | CGI-I Score at Week 6 |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in CGI-S Score |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PANSS Excited Component Score |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PANSS General Psychopathology Subscale Score |
| NCT01810380 (18) [back to overview] | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety/Depression |
| NCT01810783 (1) [back to overview] | Safety and Tolerability |
| NCT01837797 (2) [back to overview] | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) |
| NCT01837797 (2) [back to overview] | Number of Adverse Events |
| NCT01838681 (18) [back to overview] | Full Remission During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Response at Week 6 During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Total Time in Remission During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Time to Full Remission During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Full Remission Sustained During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Remission at Week 24 in the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Remission at Week 6 During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Response at Week 24 During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Change From Randomisation to Week 24 in SDS Total Score During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Change From Randomisation to Week 6 in CGI-S Score During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Change From Randomisation to Week 6 in MADRS Total Score During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Change From Randomisation to Week 6 in Q-LES-Q (SF) Total Score During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Change From Randomisation to Week 6 in SDS Total Score During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Full Functional Remission During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Full Global Score Remission During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Change From Randomisation to Week 24 in CGI-S Score During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Change From Randomisation to Week 24 in MADRS Total Score During the Randomised Treatment Period |
| NCT01838681 (18) [back to overview] | Change From Randomisation to Week 24 in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q (SF)) Total Score During the Randomised Treatment Period |
| NCT01854944 (17) [back to overview] | Mean Change From Baseline in Clinical Global Impression-Improvement (CGI-I) Score |
| NCT01854944 (17) [back to overview] | Peak (Maximal) Concentration of Drug in Plasma (Cmax) for Brexpiprazole and Its Metabolite DM-3411 |
| NCT01854944 (17) [back to overview] | Change in Percentage 5-HT2A Receptor Occupancy |
| NCT01854944 (17) [back to overview] | Change in Percentage 5-HT1A Receptor Occupancy |
| NCT01854944 (17) [back to overview] | Change in Occupancy at Serotonin Transporter (SERT) |
| NCT01854944 (17) [back to overview] | Area Under the Concentration-time Curve (AUCτ) During a Dosing Interval at Steady-state for Brexpiprazole and Its Metabolite DM-3411 |
| NCT01854944 (17) [back to overview] | Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score |
| NCT01854944 (17) [back to overview] | Apparent Clearance of Drug From Plasma After Extravascular Administration (CL/F; Only Brexpiprazole) |
| NCT01854944 (17) [back to overview] | Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score |
| NCT01854944 (17) [back to overview] | Change in Percentage Dopamine D2/D3 Receptor Occupancy |
| NCT01854944 (17) [back to overview] | Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score |
| NCT01854944 (17) [back to overview] | Time to Maximum (Peak) Plasma Concentration (Tmax) for Brexpiprazole and Its Metabolite DM-3411 |
| NCT01854944 (17) [back to overview] | Percentage of Participants Who Reported at Least One Occurrence of Suicidality, Suicidal Behavior and Suicidal Ideation on the Columbia-Suicide Severity Rating Scale (C-SSRS) |
| NCT01854944 (17) [back to overview] | Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score |
| NCT01854944 (17) [back to overview] | Mean Change From Baseline in Positive and Negative Symptom Scale (PANSS) Total Score |
| NCT01854944 (17) [back to overview] | Mean Change From Baseline in PANSS Negative Subscale Score |
| NCT01854944 (17) [back to overview] | Mean Change From Baseline in PANNS Positive Subscale Score |
| NCT01862640 (2) [back to overview] | Change From Baseline In The Clinical Global Impression-Severity Of Illness (CGI-S) Score, As Related To Symptoms Of Agitation After 12 Weeks Of Brexpiprazole Treatment |
| NCT01862640 (2) [back to overview] | Change From Baseline In The Cohen-Mansfield Agitation Inventory (CMAI) Total Score After 12 Weeks Of Brexpiprazole Treatment |
| NCT01922258 (2) [back to overview] | Change From Baseline to Week 12/Early Termination in the Cohen-Mansfield Agitation Inventory (CMAI) Total Score |
| NCT01922258 (2) [back to overview] | Change in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Symptoms of Agitation |
| NCT01942733 (26) [back to overview] | Percentage of MADRS Responders at Week 8 |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 on Number of Awakenings (NAW) as Assessed by Actigraphy (ACT) |
| NCT01942733 (26) [back to overview] | Change From Baseline to Week 8 in ISI Total Score |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 in Circadian and Biological Rhythm |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography (Continued) |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 on Sleep Quality as Assessed by Actigraphy (ACT) Parameters |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Parameters |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) |
| NCT01942733 (26) [back to overview] | Change From Baseline to Week 8 on BL-VAS-s (Morning) Score |
| NCT01942733 (26) [back to overview] | Change From Baseline to Week 8 on BL-VAS-s Scores (Noon) |
| NCT01942733 (26) [back to overview] | Change From Baseline to Week 8 on ESS Total Score |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 in Number of Lapses as Assessed Using a PVT Device |
| NCT01942733 (26) [back to overview] | Change From Baseline to Week 8 in CPFQ Total Score |
| NCT01942733 (26) [back to overview] | Change From Baseline to Week 8 in CGI-S Score |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 on Sleep Efficiency (SE) as Assessed by Actigraphy (ACT) |
| NCT01942733 (26) [back to overview] | CGI-I Score at Week 8 |
| NCT01942733 (26) [back to overview] | Change From Baseline to Week 8 in MADRS Total Score |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 in Response Speed as Assessed Using a PVT Device |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Number of Awakenings (PSG NAW) |
| NCT01942733 (26) [back to overview] | Change From Baseline to Week 8 in BRIAN Total Score |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Sleep Efficiency (PSG SE) |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Number of Awakenings (NAW) |
| NCT01942733 (26) [back to overview] | Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Sleep Efficiency (SE) |
| NCT01942733 (26) [back to overview] | Percentage of MADRS Remitters at Week 8 |
| NCT01942733 (26) [back to overview] | Change From Baseline to Week 8 on BL-VAS-s (Evening) Score |
| NCT01942785 (26) [back to overview] | Change From Week 6 to Week 10 in BIS-11 Total Score |
| NCT01942785 (26) [back to overview] | Change From Week 6 to Week 10 in CGI-S Score |
| NCT01942785 (26) [back to overview] | Change From Week 6 to Week 10 in Delay Discounting - MCQ Scores |
| NCT01942785 (26) [back to overview] | Change From Week 6 to Week 10 in KSQ Anger-hostility Subscore |
| NCT01942785 (26) [back to overview] | Change From Week 6 to Week 10 in KSQ Depression Subscore |
| NCT01942785 (26) [back to overview] | Change From Week 6 to Week 10 in SIS Item 1 Score |
| NCT01942785 (26) [back to overview] | Change From Week 6 to Week 10 in SIS Total Score |
| NCT01942785 (26) [back to overview] | CGI-I Score at Week 6 Patients With a Pre-defined Baseline BIS-11 Total Score |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in CGI-S Score in Patients With a Pre-defined Baseline BIS-11 Total Score |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in Delay Discounting - Log-transformed EDT DPDT Scores |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in MADRS Total Score in Patients With a Pre-defined Baseline BIS-11 Total Score |
| NCT01942785 (26) [back to overview] | Shift From Baseline to Week 6 in Anger Attacks (AAQ) |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in IDS-C30 Total Score |
| NCT01942785 (26) [back to overview] | CGI-I Score at Week 6 |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in BIS-11 Total Score |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in CGI-S Score |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in CPFQ Total Score |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in Delay Discounting - EDT DRT Score |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in Delay Discounting - Log-transformed MCQ Scores |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in IDS-C30 Item 6 Score |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in KSQ Anger-hostility Subscore |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in KSQ Depression Subscore |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in KSQ Total Score |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in MADRS Total Score |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in SIS Item 1 Score |
| NCT01942785 (26) [back to overview] | Change From Baseline to Week 6 in SIS Total Score |
| NCT01944969 (3) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events |
| NCT01944969 (3) [back to overview] | Number of Withdrawals |
| NCT01944969 (3) [back to overview] | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) |
| NCT01987960 (2) [back to overview] | Global Clinical Impression Severity of Illness (CGI-S) Score |
| NCT01987960 (2) [back to overview] | PTSD Symptoms Using CAPS-2 Total Score |
| NCT02012218 (1) [back to overview] | Mean Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Delay and Probability Discounting Task (DPDT) Scores |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Go/No-Go Task for Mean Reaction Time |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Go/No-Go Task for P-inhibition Failures |
| NCT02013531 (19) [back to overview] | Percentage of Participants With CGI-I Response Rate |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Food Delay Discounting Task |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Barratt Impulsiveness Scale 11-item (BIS-11) Total Score |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Hamilton Depression Rating Scale (HAM-D17) Total Score |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Kellner Symptom Questionnaire (KSQ) |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Money Delay Discounting Task |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Score |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline to Week 6 in the Number of Impulsive Choices in the Delayed Reward Task (DRT) |
| NCT02013531 (19) [back to overview] | Mean Change in Clinical Global Impression-Severity (CGI-S) Total Score |
| NCT02013531 (19) [back to overview] | Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 6. |
| NCT02013531 (19) [back to overview] | Percentage of Participants With a MADRS Remission |
| NCT02013531 (19) [back to overview] | Percentage of Participants With a MADRS Response |
| NCT02013531 (19) [back to overview] | Mean Change From Baseline in Delay Discounting Task - Monetary Choice Questionnaire (MCQ) Score |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in the Number of Impulsive Choices in the Delayed Reward Task (DRT) |
| NCT02013609 (20) [back to overview] | Percentage of Participants With MADRS Remission |
| NCT02013609 (20) [back to overview] | Percentage of Participants With MADRS Response |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Go/No-Go Task (Mean Reaction Time) |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Go/No-Go Task (P-inhibition Failure) |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Sheehan Disability Scale (SDS) Single Item Sub-scores |
| NCT02013609 (20) [back to overview] | Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 12 |
| NCT02013609 (20) [back to overview] | Number of Participants With CGI-I Response |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Delay and Probability Discounting Task (DPDT) |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline in Delay Discounting Task - Monetary Choice Questionnaire (MCQ) k Value |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline in Food Delay Discounting Task (DDT) |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline in Money Delay Discounting Task |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Barratt Impulsiveness Scale 11-Item (BIS-11) Total Score |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Clinical Global Impression-Severity (CGI-S) Total Score |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Hamilton Depression Rating Scale (HAM-D17) Total Score |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Kellner Symptom Questionnaire (KSQ) Total Score |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Sheehan Disability Scale (SDS) 3-item Total/Summed Score |
| NCT02013609 (20) [back to overview] | Mean Change From Baseline to Week 12 in Social Adaptation Self-evaluation Scale (SASS) Total Score |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Delay Discounting Task - Monetary Choice Questionnaire (MCQ) Scores |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Food Delay Discounting Task |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Money Delay Discounting Task |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Personal and Social Performance (PSP) Total Score |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Pittsburgh Sleep Quality Index (PSQI) Total Score |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Positive and Negative Syndrome Scale (PANSS) Total Score |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Delay and Probability Discounting Task (DPDT) - Experiential Discounting Task Scores |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Specific Levels of Functioning (SLOF) Total Score |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 Scores of the Following Negative Scale Items: Active Social Avoidance, Emotional Withdrawal, Passive/Apathetic Social Withdrawal, and Difficulty in Abstract Thinking |
| NCT02013622 (17) [back to overview] | CGI-I Response Rate |
| NCT02013622 (17) [back to overview] | Mean Clinical Global Impression-Improvement (CGI-I) Score |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Treatment Satisfaction Questionnaire for Medication (TSQM) Total Score |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Go/No-Go Task (P-inhibition Failures) |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Go/No-Go Task (Mean Reaction Time) |
| NCT02013622 (17) [back to overview] | Change From Baseline to Week 16 in the Mean Number of Impulsive Choices in the Delayed Reward Task (DRT) |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Barratt Impulsiveness Scale (BIS) 11-Item |
| NCT02013622 (17) [back to overview] | Mean Change From Baseline to Week 16 in Clinical Global Impression-Severity (CGI-S) Score |
| NCT02054702 (12) [back to overview] | Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score |
| NCT02054702 (12) [back to overview] | Change From Baseline to Week 6 in Specific Levels of Functioning Scale (SLOF) Total Score |
| NCT02054702 (12) [back to overview] | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score |
| NCT02054702 (12) [back to overview] | Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11 Item) Total Score |
| NCT02054702 (12) [back to overview] | Change From Baseline in Cognitive Test Battery Scores of Identification Task |
| NCT02054702 (12) [back to overview] | Change From Baseline in Cognitive Test Battery Scores of Groton Maze Learning (GML) |
| NCT02054702 (12) [back to overview] | Change From Baseline in Cognitive Test Battery Scores of Detection Task |
| NCT02054702 (12) [back to overview] | Change From Baseline in Cognitive Test Battery of Early Phase Battery Score |
| NCT02054702 (12) [back to overview] | Change From Baseline in Cognitive Test Battery Composite Score |
| NCT02054702 (12) [back to overview] | Change From Baseline in Cognitive Test Battery Scores of One Card Learning Task |
| NCT02054702 (12) [back to overview] | Response Rate by Study Week |
| NCT02054702 (12) [back to overview] | Mean Change in Clinical Global Impression-Improvement (CGI-I) Score at Week 6 |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 6 in Stop Signal Reaction Time Task (SSRT) Task Behavior |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 6 in Go/No-go Task Behavior |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 3 in SSRT Task Behavior |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 3 in Go/No-go Task Behavior |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 3 in fMRI BOLD Activation Score in the Right VLPFC, Scanned by fMRI During Performance of Tasks Associated With Impulsivity (SSRT Task, Go/No-go Task) |
| NCT02194933 (24) [back to overview] | Change From Baseline Brain Activation in the VLPFC Based on Change From Baseline to Week 6 in fMRI BOLD Activation Score in the Right VLPFC During Performance of the SSRT Task |
| NCT02194933 (24) [back to overview] | Clinical Global Impression - Improvement Scale (CGI-I) Score at Week 6 |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 3 in BIS-11 |
| NCT02194933 (24) [back to overview] | CGI-I Score at Week 3 |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 6 in PANSS Positive Subscale Score |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 6 in PANSS Negative Subscale Score |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 6 in Monetary Choice Questionnaire (MCQ) Score |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 6 in Continuous Performance Task (CPT) Behavior |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11) |
| NCT02194933 (24) [back to overview] | Change From Baseline Brain Activation in the Ventrolateral Prefrontal Cortex (VLPFC) Based on Change From Baseline to Week 6 in fMRI Blood Oxygen-level Dependent (BOLD) Activation Score in the Right VLPFC During Performance of the Go/No-go Task |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 3 in PANSS Total Score |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 3 in PANSS Positive Subscale Score |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 3 in PANSS Negative Subscale Score |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 3 in MCQ Score |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 3 in CGI-S Score |
| NCT02194933 (24) [back to overview] | Change From Baseline to Week 3 in CPT Behavior |
| NCT02196506 (4) [back to overview] | Change in the Sheehan Disability Scale (SDS) From Baseline to End of Treatment |
| NCT02196506 (4) [back to overview] | Change From End of Phase A to End of Phase B in MADRS Total Score for the Subpopulation With <25% Improvement From Baseline of Phase A to End of Phase A in MADRS Total Score |
| NCT02196506 (4) [back to overview] | Change From End of Phase A to End of Phase B in MADRS Total Score for the Subpopulations With Anxious Distress as Specified in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). |
| NCT02196506 (4) [back to overview] | Change in the Montgomery-Asberg Depression |
| NCT02400346 (1) [back to overview] | Number of Patients With Treatment-Emergent Adverse Events |
| NCT02875080 (2) [back to overview] | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞) of OPC-34712 |
| NCT02875080 (2) [back to overview] | Maximum Plasma Concentration (Cmax) of OPC-34712 |
| NCT03033069 (1) [back to overview] | Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score |
| NCT03149991 (11) [back to overview] | Safety and Tolerability Outcomes: 12-lead Electrocardiogram (ECG) - Number of Participants With Abnormal ECGs |
| NCT03149991 (11) [back to overview] | Change From Baseline on Symptoms of Depression Questionnaire (SDQ) |
| NCT03149991 (11) [back to overview] | Safety and Tolerability Outcomes: Treatment-emergent Adverse Events (Number of Participants Reporting) |
| NCT03149991 (11) [back to overview] | Safety and Tolerability Outcomes: Treatment-emergent Adverse Events (Average Number Per Person Per Group) |
| NCT03149991 (11) [back to overview] | Long-term Sustained Response, as Measured by Achieving a 50% Reduction on the Montgomery-Asberg Depression Rating Scale (MADRS) on Day 28 (Number and Percentage of Participants Achieving Sustained Response Reported) |
| NCT03149991 (11) [back to overview] | Safety and Tolerability Outcomes: Number of Participants With Abnormal Vital Signs (Elevated Heart Rate) |
| NCT03149991 (11) [back to overview] | Safety and Tolerability Outcomes: Suicidal Ideation and Behavior |
| NCT03149991 (11) [back to overview] | Safety and Tolerability Outcomes: Number of Participants With Abnormal Laboratory Test Results |
| NCT03149991 (11) [back to overview] | Safety and Tolerability Outcomes: 12-lead Electrocardiogram (ECG) - Total Number of Abnormal ECGs |
| NCT03149991 (11) [back to overview] | Safety and Tolerability Outcomes: Number of Participants With Abnormal Vital Signs (Elevated Blood Pressure) |
| NCT03149991 (11) [back to overview] | Efficacy on Secondary Outcome Variables |
| NCT03198078 (22) [back to overview] | Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score |
| NCT03198078 (22) [back to overview] | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score |
| NCT03198078 (22) [back to overview] | Change From Baseline to Week 6 in Clinical Global Impression Severity (CGI-S) Scale Score |
| NCT03198078 (22) [back to overview] | Mean Change From Baseline in Height |
| NCT03198078 (22) [back to overview] | Mean Change From Baseline in Waist Circumference |
| NCT03198078 (22) [back to overview] | Number of Participants With Treatment-emergent AEs (TEAEs), Serious TEAEs, and TEAEs Graded by Severity |
| NCT03198078 (22) [back to overview] | Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale |
| NCT03198078 (22) [back to overview] | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters |
| NCT03198078 (22) [back to overview] | Number of Participants With Potentially Clinically Relevant Laboratory Test Values |
| NCT03198078 (22) [back to overview] | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs |
| NCT03198078 (22) [back to overview] | Number of Participants With Adverse Events (AEs) and Trial Discontinuation Due to AEs |
| NCT03198078 (22) [back to overview] | Change From Baseline to Week 6 in PANSS Positive and Negative Sub-Scales Scores |
| NCT03198078 (22) [back to overview] | Percentage of Participants Achieving Remission |
| NCT03198078 (22) [back to overview] | Number of Participants With At Least One Occurrence of Suicidal Behavior or Suicidal Ideation as Recorded on Columbia-Suicide Severity Rating Scale (C-SSRS) |
| NCT03198078 (22) [back to overview] | Mean Clinical Global Impression Improvement (CGI-I) Scale Score at Week 6 |
| NCT03198078 (22) [back to overview] | Change From Baseline to Week 6 in Children's Global Assessment Scale (CGAS) Total Score |
| NCT03198078 (22) [back to overview] | Change From Baseline in Simpson Angus Scale (SAS) Total Score |
| NCT03198078 (22) [back to overview] | Number of Participants With Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) |
| NCT03198078 (22) [back to overview] | Mean Change From Baseline in Weight |
| NCT03198078 (22) [back to overview] | Percentage of Participants Achieving Response |
| NCT03198078 (22) [back to overview] | Mean Change From Baseline in Body Mass Index (BMI) |
| NCT03198078 (22) [back to overview] | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score |
| NCT03257865 (2) [back to overview] | Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3 |
| NCT03257865 (2) [back to overview] | Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3 |
| NCT03259555 (2) [back to overview] | Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3 |
| NCT03259555 (2) [back to overview] | Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3 |
| NCT03287869 (1) [back to overview] | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity |
| NCT03418675 (11) [back to overview] | Sheehan Disability Scale (SDS) |
| NCT03418675 (11) [back to overview] | Self Report Version of Zanarini Scale |
| NCT03418675 (11) [back to overview] | Quality of Life Inventory (QOLI) |
| NCT03418675 (11) [back to overview] | MINI International Neuropsychiatric Interview |
| NCT03418675 (11) [back to overview] | Borderline Evaluation of Severity Over Time (BEST) |
| NCT03418675 (11) [back to overview] | Columbia Suicide Severity Rating Scale (CSSRS) |
| NCT03418675 (11) [back to overview] | Hamilton Depression Rating Scale (HAM-D) |
| NCT03418675 (11) [back to overview] | Hamilton Anxiety Rating Scale (HAM-A) |
| NCT03418675 (11) [back to overview] | Barratt Impulsiveness Scale (BIS) |
| NCT03418675 (11) [back to overview] | Zanarini Rating Scale for Borderline Personality Disorder |
| NCT03418675 (11) [back to overview] | Symptom Checklist-90 Revised |
| NCT03427892 (13) [back to overview] | Stroop Task |
| NCT03427892 (13) [back to overview] | High Sensitivity C-Reactive Protein (Hs-CRP) |
| NCT03427892 (13) [back to overview] | Quality of Life in Bipolar Disorder (QOLBD) |
| NCT03427892 (13) [back to overview] | Rey Auditoy Verbal Learning Test |
| NCT03427892 (13) [back to overview] | Simpson Angus Scale |
| NCT03427892 (13) [back to overview] | Systematic Assessment For Treatment Emergent Events |
| NCT03427892 (13) [back to overview] | The Inventory of Depressive Symptomatology Self-Report (IDS-SR30) |
| NCT03427892 (13) [back to overview] | The Montgomery-Asberg Depression Rating Scale (MADRS) |
| NCT03427892 (13) [back to overview] | Abnormal Involuntary Movement Scale |
| NCT03427892 (13) [back to overview] | Barnes Akathisia Scale |
| NCT03427892 (13) [back to overview] | Columbia Suicide Severity Rating Scale |
| NCT03427892 (13) [back to overview] | Young Mania Rating Scale (YMRS) |
| NCT03427892 (13) [back to overview] | Trail Making Test (TMT) |
| NCT03538691 (8) [back to overview] | Phase C: Change From Baseline for Randomization Phase in Sheehan Disability Scale (SDS) Mean Total Score at Week 46 |
| NCT03538691 (8) [back to overview] | Phase C: Percentage of Participants Meeting Any Relapse Criteria |
| NCT03538691 (8) [back to overview] | Phase C: Time-to-functional Relapse Based on SDS Criteria |
| NCT03538691 (8) [back to overview] | Phase C: Time-to-Relapse by Any Criteria as Defined in Blinded Addendum |
| NCT03538691 (8) [back to overview] | Phase C: Change From Baseline for Randomization Phase in Each of the SDS Individual Item Scores at Week 46 |
| NCT03538691 (8) [back to overview] | Phase C: Change From Baseline for Randomization Phase in MADRS Total Score at Week 46 |
| NCT03538691 (8) [back to overview] | Phase C: Percentage of Participants Maintaining Remission |
| NCT03538691 (8) [back to overview] | Phase C: Change From Baseline for Randomization Phase in CGI-S Score at Week 46 |
| NCT03548584 (9) [back to overview] | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period |
| NCT03548584 (9) [back to overview] | Change From Baseline to Week 12 in CMAI Subscale Scores |
| NCT03548584 (9) [back to overview] | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period |
| NCT03548584 (9) [back to overview] | Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation |
| NCT03548584 (9) [back to overview] | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period |
| NCT03548584 (9) [back to overview] | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period |
| NCT03548584 (9) [back to overview] | Change From Baseline to Week 12 in the CMAI Total Score |
| NCT03548584 (9) [back to overview] | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period |
| NCT03548584 (9) [back to overview] | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period |
| NCT03557931 (8) [back to overview] | Number of Participants With Clinically Significant Differences in Simpson Angus Scale (SAS) Values |
| NCT03557931 (8) [back to overview] | Number of Participants With Adverse Event (AE) |
| NCT03557931 (8) [back to overview] | Number of Participants With Clinically Significant Differences in Barnes Akathisia Rating Scale (BARS) Values |
| NCT03557931 (8) [back to overview] | Concentration at Trough Level (Ctrough) for ASP4345 |
| NCT03557931 (8) [back to overview] | Number of Participants With Clinically Significant Differences in Columbia-Suicide Severity Rating Scale (C-SSRS) Values |
| NCT03557931 (8) [back to overview] | Change From Baseline to Week 12/EoT in University of California San Diego Performance-based Skills Assessment-2 Extended Range (UPSA-2-ER) Total Score |
| NCT03557931 (8) [back to overview] | Change From Baseline to Week 12/End of Treatment (EoT) in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score |
| NCT03557931 (8) [back to overview] | Number of Participants With Clinically Significant Differences in Abnormal Involuntary Movement Scale (AIMS) Values |
| NCT03594123 (1) [back to overview] | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity |
| NCT03902574 (2) [back to overview] | Maximum (Peak) Plasma Concentration (Cmax) of Brexpiprazole |
| NCT03902574 (2) [back to overview] | Area Under the Concentration-time Curve Calculated to the Last Observable Concentration at Time t (AUCt) of Brexpiprazole |
Change From End of Phase A (Week 8 Visit) in Mean CGI-S Score for Every Study Week Visit in Phase B Other Than the Week 14 Visit.
CGI-S items are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale from 1 through 7. CGI-S was assessed at screening, baseline and each subsequent visit from Week 1 through Week 14. (NCT00797966)
Timeframe: Week 8 to each of Week 9, 10, 11, 12 and 13.
| Intervention | Units on a scale (Mean) |
|---|
| Week 9 (N=62,117,116,121) | Week 10 (N=62,119,118,126) | Week 11 (N=62,119,118,126) | Week 12 (N=62,119,118,126) | Week 13 (N=62,119,118,126) |
|---|
| OPC-34712 0.15 mg Fixed Dose | -0.21 | -0.42 | -0.53 | -0.76 | -0.74 |
,| OPC-34712 0.5 ± 0.25 mg Low Dose | -0.26 | -0.39 | -0.53 | -0.66 | -0.78 |
,| OPC-34712 1.5 ± 0.5 mg High Dose | -0.33 | -0.61 | -0.69 | -0.86 | -0.88 |
,| Placebo | -0.21 | -0.40 | -0.47 | -0.52 | -0.59 |
Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Q-LES-Q-SF Item 16 Score (Overall Life Satisfaction).
The Q-LES-Q (Short Form) is a self-report measure designed to enable physicians to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. According to the scoring system suggested for this questionnaire, item 16 (Overall Life Satisfaction) will yield a separate subscore. (NCT00797966)
Timeframe: Week 8 to Week 14
| Intervention | Units on a scale (Mean) |
|---|
| OPC-34712 0.15 mg Fixed Dose | 0.30 |
| OPC-34712 0.5 ± 0.25 mg Low Dose | 0.30 |
| OPC-34712 1.5 ± 0.5 mg High Dose | 0.35 |
| Placebo | 0.28 |
Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Q-LES-Q-SF Item 15 Score (Satisfaction With Medication).
The Q-LES-Q (Short Form) is a self-report measure designed to enable physicians to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. According to the scoring system suggested for this questionnaire, item 15 (Satisfaction with Medication) will yield a separate subscore. (NCT00797966)
Timeframe: Week 8 to Week 14
| Intervention | Units on a scale (Mean) |
|---|
| OPC-34712 0.15 mg Fixed Dose | 0.02 |
| OPC-34712 0.5 ± 0.25 mg Low Dose | 0.01 |
| OPC-34712 1.5 ± 0.5 mg High Dose | 0.02 |
| Placebo | 0.00 |
Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Clinical Global Impression - Severity of Illness Scale (CGI-S) Score.
CGI-S items are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale from 1 through 7. CGI-S was assessed at screening, baseline and each subsequent visit from Week 1 through Week 14. (NCT00797966)
Timeframe: Week 8 to Week 14
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| OPC-34712 0.15 mg Fixed Dose | -0.83 |
| OPC-34712 0.5 ± 0.25 mg Low Dose | -0.81 |
| OPC-34712 1.5 ± 0.5 mg High Dose | -1.06 |
| Placebo | -0.71 |
Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Depression Rating Scale (HAM-D17) Score.
"The HAM-D17 is utilized as a secondary assessment of a participant's level of depression. The HAM-D (17-Item) consists of 17 items. Eight items are rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) are rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 is the best rating and the highest score (2 or 4) is the worst rating. The possible total scores are from 0 to 52." (NCT00797966)
Timeframe: Week 8 to Week 14
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| OPC-34712 0.15 mg Fixed Dose | -5.77 |
| OPC-34712 0.5 ± 0.25 mg Low Dose | -5.28 |
| OPC-34712 1.5 ± 0.5 mg High Dose | -6.59 |
| Placebo | -5.23 |
Clinical Global Impression-Improvement Scale (CGI-I) Score at Each Study Week Visit in Phase B.
CGI-I items are: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) will be set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. CGI-I was assessed at each visit in Phase B, and improvement is judged with respect to the participant's condition at baseline. CGI-I was also assessed at each visit in Phase B, but in that phase improvement is judged with respect to the partcipant's condition at the end of Phase A. (NCT00797966)
Timeframe: Week 8 to each of Week 9, 10, 11, 12, 13 and 14.
| Intervention | Units on a scale (Mean) |
|---|
| Week 9 (N=62, 117, 116, 121) | Week 10 (N=62, 119, 118, 126) | Week 11 (N=62, 119, 118, 126) | Week 12 (N=62, 119, 118, 126) | Week 13 (N=62, 119, 118, 126) | Week 14 (N=62, 119, 118, 126) |
|---|
| OPC-34712 0.15 mg Fixed Dose | 3.39 | 3.16 | 2.94 | 2.87 | 2.85 | 2.74 |
,| OPC-34712 0.5 ± 0.25 mg Low Dose | 3.30 | 3.19 | 3.02 | 2.90 | 2.76 | 2.78 |
,| OPC-34712 1.5 ± 0.5 mg High Dose | 3.20 | 2.95 | 2.80 | 2.70 | 2.64 | 2.52 |
,| Placebo | 3.31 | 3.11 | 2.94 | 2.95 | 2.90 | 2.83 |
Percentage of Participants With CGI-I Response From End of Phase A (Week 8 Visit).
CGI-I response is defined as CGI-I of 1 [very much improved] or 2 [much improved]. (NCT00797966)
Timeframe: Week 9, 10, 11, 12, 13 and 14.
| Intervention | percentage of participants (Number) |
|---|
| Week 9 (N=62, 117, 116, 121) | Week 10 (N=62, 119, 118, 126) | Week 11 (N=62, 119, 118, 126) | Week 12 (N=62, 119, 118, 126) | Week 13 (N=62, 119, 118, 126) | Week 14 (N=62, 119, 118, 126) |
|---|
| OPC-34712 0.15 mg Fixed Dose | 16.1 | 25.8 | 32.3 | 35.5 | 37.1 | 38.7 |
,| OPC-34712 0.5 ± 0.25 mg Low Dose | 11.1 | 17.6 | 29.4 | 33.6 | 37.0 | 37.0 |
,| OPC-34712 1.5 ± 0.5 mg High Dose | 14.7 | 24.6 | 35.6 | 42.4 | 49.2 | 52.5 |
,| Placebo | 14.9 | 27.0 | 29.4 | 31.7 | 33.3 | 41.3 |
Percentage of Participants With MADRS Response From End of Phase A (Week 8 Visit).
A MADRS response was defined as >/= 50% reduction in MADRS Total Score from end of Phase A (Week 8 visit). (NCT00797966)
Timeframe: Week 8 to each of Week 9, 10, 11, 12, 13 and 14.
| Intervention | Percentage of participants (Number) |
|---|
| Week 9 (N=61, 117, 116, 121) | Week 10 (N=62, 119, 118, 126) | Week 11 (N=62, 119, 118, 126) | Week 12 (N=62, 119, 118, 126) | Week 13 (N=62, 119, 118, 126) | Week 14 (N=62, 119, 118, 126) |
|---|
| OPC-34712 0.15 mg Fixed Dose | 4.92 | 8.06 | 19.4 | 30.6 | 24.2 | 27.4 |
,| OPC-34712 0.5 ± 0.25 mg Low Dose | 6.84 | 8.40 | 15.1 | 15.1 | 22.7 | 20.2 |
,| OPC-34712 1.5 ± 0.5 mg High Dose | 2.59 | 11.0 | 18.6 | 25.4 | 25.4 | 34.7 |
,| Placebo | 8.26 | 9.52 | 13.5 | 11.9 | 18.3 | 19.8 |
Percentage of Participants With MADRS Remission From End of Phase A (Week 8 Visit).
A MADRS remission was defined as MADRS Total Score /= 50% reduction in MADRS Total Score from end of Phase A (Week 8 visit). (NCT00797966)
Timeframe: Week 8 to each of Week 9, 10, 11, 12, 13 and 14.
| Intervention | Percentage of participants (Number) |
|---|
| Week 9 (N=61, 117, 116, 121) | Week 10 (N=62, 119, 118, 126) | Week 11 (N=62, 119, 118, 126) | Week 12 (N=62, 119, 118, 126) | Week 13 (N=62, 119, 118, 126) | Week 14 (N=62, 119, 118, 126) |
|---|
| OPC-34712 0.15 mg Fixed Dose | 3.28 | 8.06 | 12.9 | 21.0 | 19.4 | 22.6 |
,| OPC-34712 0.5 ± 0.25 mg Low Dose | 1.71 | 5.04 | 10.1 | 10.1 | 16.8 | 15.1 |
,| OPC-34712 1.5 ± 0.5 mg High Dose | 1.72 | 10.2 | 14.4 | 19.5 | 15.3 | 23.7 |
,| Placebo | 4.13 | 8.73 | 11.1 | 10.3 | 15.1 | 13.5 |
Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score.
"The MADRS is utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale 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. The possible Total scores are from 0 to 60. The MADRS Total Score was unevaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items were recorded, the MADRS Total Score was the mean of the recorded items multiplied by 10 and then rounded to the first decimal place." (NCT00797966)
Timeframe: Week 8 to Week 14
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| OPC-34712 0.15 mg Fixed Dose | -6.62 |
| OPC-34712 0.5 ± 0.25 mg Low Dose | -6.46 |
| OPC-34712 1.5 ± 0.5 mg High Dose | -8.23 |
| Placebo | -6.09 |
Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Score (the Mean of 3 Individual Item Scores).
The Sheehan Disability Scale (SDS) is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable. (NCT00797966)
Timeframe: Week 8 to Week 14
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| OPC-34712 0.15 mg Fixed Dose | -0.84 |
| OPC-34712 0.5 ± 0.25 mg Low Dose | -0.80 |
| OPC-34712 1.5 ± 0.5 mg High Dose | -1.27 |
| Placebo | -0.61 |
Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score.
"The IDS-SR is a 30-item self-report measure used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorders. The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. The IDS-SR Total Score is the sum of ratings of 28 item scores. The possible IDS-SR Total Score ranges from 0 to 84. The IDS-SR Total Score was un-evaluable if less than 23 of the 28 items are recorded. If the number of items was at least 23 and at most 27, the IDS-SR Total Score will be the mean of the recorded items multiplied by 28 and then rounded to the first decimal place." (NCT00797966)
Timeframe: Week 8 to each of Week 9, 10, 11, 12, 13 and 14
| Intervention | Units on a scale (Mean) |
|---|
| Week 9 (N=61, 117,116,121) | Week 10 (N=62, 119, 118, 126) | Week 11 (N=62, 119, 118, 126) | Week 12 (N=62, 119, 118, 126) | Week 13 (N=62, 119, 118, 126) | Week 14 (N=62, 119, 118, 126) |
|---|
| OPC-34712 0.15 mg Fixed Dose | -0.98 | -2.13 | -3.58 | -5.11 | -5.34 | -5.55 |
,| OPC-34712 0.5 ± 0.25 mg Low Dose | -1.88 | -2.58 | -3.41 | -3.77 | -5.22 | -4.96 |
,| OPC-34712 1.5 ± 0.5 mg High Dose | -2.04 | -4.08 | -4.82 | -5.77 | -5.65 | -6.74 |
,| Placebo | -0.98 | -1.62 | -2.09 | -2.07 | -2.37 | -3.08 |
Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than the Week 14 Visit.
"The MADRS is utilized as the primary efficacy assessment of a patient's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale 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. The possible Total scores are from 0 to 60. The MADRS Total Score was unevaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items were recorded, the MADRS Total Score was the mean of the recorded items multiplied by 10 and then rounded to the first decimal place." (NCT00797966)
Timeframe: Week 8 to each of Week 9, 10, 11, 12 and 13.
| Intervention | Units on a scale (Mean) |
|---|
| Week 9 (N=61,117,116,121) | Week 10 (N=62,119,118,126) | Week 11 (N=62,119,118,126) | Week 12 (N=62,119,118,126) | Week 13 (N=62,119,118,126) |
|---|
| OPC-34712 0.15 mg Fixed Dose | -2.13 | -3.69 | -5.53 | -6.97 | -6.90 |
,| OPC-34712 0.5 ± 0.25 mg Low Dose | -3.00 | -3.78 | -5.71 | -6.31 | -6.76 |
,| OPC-34712 1.5 ± 0.5 mg High Dose | -2.75 | -4.97 | -5.88 | -7.01 | -7.18 |
,| Placebo | -2.48 | -3.64 | -4.40 | -4.41 | -5.47 |
Change From Baseline (End of Phase A) in Sleep Improvement Measured by ISI for Item 2 Score (Difficulty Staying Asleep) to End of Phase B
The ISI is self-report instrument that has been validated specifically for measuring the perceived severity of insomnia. The scale was composed of a total of 7 items based on self-report questionnaire based on several indicators assessing the perceived severity of difficulties initiating sleep, staying asleep, and early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Each item was rated on a scale from 0 (none) to 4 (higher score indicating greater impairment/concern). A total score ranging from 0 to 28 was calculated from the sum of the individual item scores, higher scores indicate increased severity of insomnia. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -0.04 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -0.37 |
Change From Baseline (End of Phase A) in Sleep Improvement Measured by Insomnia Severity Index (ISI) Total Score to End of Phase B
The ISI is self-report instrument that has been validated specifically for measuring the perceived severity of insomnia. The scale was composed of a total of 7 items based on self-report questionnaire based on several indicators assessing the perceived severity of difficulties initiating sleep, staying asleep, and early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Each item was rated on a scale from 0 (none) to 4 (higher score indicating greater impairment/concern). A total score ranging from 0 to 28 was calculated from the sum of the individual item scores, higher scores indicate increased severity of insomnia. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -1.05 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -1.62 |
Change From Baseline (End of Phase A) in RVP Total False Alarms Score as Measured by CANTAB to End of Phase B
RVP task tested continuous performance and visual sustained attention. In center of computer screen, digits from 2- 9 appear inside a white box in pseudorandom order at a rate of 100 digits per minute. Participants must touch press pad when they detect a series of target digit sequences (e.g., 2-4-6, 4-6-8, 3-5-7) which appeared at a rate of 9 sequences every 100 numbers. Data from RVP task were summarized in 3 ways: RVP A prime, RVP median response latency, and RVP total false alarms. False alarms were determined from number of times that participants responded outside response window of a target sequence during assessed part of test. Observed range for Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant is -26.0 to 13.00 (change from baseline) and for Phase B (Double-blind Randomization Phase): Placebo + Stimulant is -25.0 to 144.0 (change from baseline). Lower scores indicate better performance. ANCOVA model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 0.12 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | 0.58 |
Change From Baseline (End of Phase A) in the Stop Signal Task (SST) Stop Signal Reaction Time (SSRT) Score as Measured by CANTAB to End of Phase B
In SST, an arrow pointing either left or right is displayed on computer screen. Participant responded to arrow by pressing corresponding button (i.e., left or right) on press pad. If an audio tone is presented when arrow is displayed, participant inhibited response. Proportion of successful stops, and median reaction time on Go trials was measured. SST SSRT was an estimate of length of time between go stimulus and stop stimulus at which participant was able to successfully inhibit response on 50% of trials and calculated from SST reaction time on Go trials measure and SST stop signal delay (SSD) 50% measure as [reaction time on Go trials] - [SSD (50%)], where SSD (50%) measure was calculated as arithmetic mean of measured SSD, or failed stop reaction time, from completed assessment stop trials. Observed change from baseline range for Phase B: Brexpiprazole + Stimulant: -204 to 237.0 and for Phase B: Placebo + Stimulant: -176 to 113.0. Lower scores indicate better performance. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 13.41 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -4.10 |
Change From Baseline (End of Phase A) in the SWM Within Errors 4-8 Boxes Test Score as Measured by CANTAB to End of Phase B
Assessments were performed with CANTAB. SWM test assesses cognitive domain of executive function (high-level thinking and decision making). Participants search for colored tokens hidden inside boxes on screen by touching them. Critical instruction is that once a token has been found inside a box, there was never be a token hidden inside that box again, so participants must not return to a box where a token has been found. Within Errors 4-8 Boxes, which measured number of times a participant revisited a box that had already been found to be empty during the same search. Value was reported as total number of errors for 4-, 6-, and 8-box stages. Observed range for Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant is -8.00 to 6.00 (change from baseline) and for Phase B (Double-blind Randomization Phase): Placebo + Stimulant is -10.0 to 23.00 (change from baseline). A lower score reflects better performance. LOCF method was used to impute missing data. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 0.00 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | 0.30 |
Change From Baseline (End of Phase A) in Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) Total Score to End of Phase B
WRAADDS is used to measure the severity of symptoms in adults with ADHD. This structured interview consists of 28 items in 7 psychopathologic domains, which were rated by a clinical expert on a 0 to 2-point Likert scale. The psychopathologic 7 domains are inattention (6 items), impulsivity (3 items), and hyperactivity (3 items), disorganization (5 items), temper (3 items), affective lability (4 items), and emotional over-reactivity (4 items). The scale rated individual items from 0 to 2 (0=not present, 1=mild, 2=clearly present) and summarized each of the 7 categories on a 0-to-4 scale (0=none, 1=mild, 2=moderate, 3=quite a bit, 4=very much). The WRAADDS total score is defined as sum of all 28 item sub scores (range 0 - 56), higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The analysis of covariance (ANCOVA) method was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -3.93 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -3.84 |
Change From Baseline (End of Phase A) in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score to Each Timepoint in Phase B
The CGI-S is performed to rate the severity of a participant's condition on an 8-point scale ranging from 0 to 7 where 0=not assessed, 1=normal, not at all ill, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7 = among the most extremely ill participants. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change at Week 6 | Change at Week 7 | Change at Week 8 | Change at Week 9 | Change at Week 10 | Change at Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -0.75 | -0.92 | -1.03 | -1.16 | -1.17 | -1.31 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -0.71 | -0.88 | -0.97 | -1.10 | -1.28 | -1.37 |
Change From Baseline (End of Phase A) in CAARS-S:SV Inattentive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
The CAARS-S:SV is a self-reported 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). The Inattentive Symptoms Subscale is (9 items) scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 27, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change at Week 6 | Change at Week 7 | Change at Week 8 | Change at Week 9 | Change at Week 10 | Change at Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -0.87 | -1.64 | -2.08 | -2.08 | -2.43 | -2.54 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -1.16 | -1.62 | -1.93 | -2.42 | -2.84 | -3.10 |
Mean Change From Baseline (End of Phase A) in the CAARS-O:SV ADHD Symptoms Total Score (18 Items) to End of Phase B
The CAARS-O:SV is a 30 items scale with 3 subscales: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Inattentive Symptoms (9 items), DSM- IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for a total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The Mixed model repeated measures (MMRM) model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -9.02 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -9.71 |
Change From Baseline (End of Phase A) in CAARS-S:SV ADHD Index Score (12 Items) to Each Timepoint in Phase B
The CAARS-S:SV is a 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). The ADHD Index Subscale is (12 items) scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 36, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change at Week 6 | Change at Week 7 | Change at Week 8 | Change at Week 9 | Change at Week 10 | Change at Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -1.09 | -1.86 | -2.69 | -3.07 | -3.42 | -4.05 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -1.16 | -2.13 | -2.43 | -3.00 | -3.56 | -3.90 |
Change From Baseline (End of Phase A) in WRAADDS Attention + Organization Subscale Score to End of Phase B
WRAADDS is used to measure the severity of symptoms in adults with ADHD. This structured interview consists of 28 items in 7 psychopathologic domains, which were rated by a clinical expert on a 0 to 2-point Likert scale. The psychopathologic 7 domains are inattention (6 items), impulsivity (3 items), and hyperactivity (3 items), disorganization (5 items), temper (3 items), affective lability (4 items), and emotional over-reactivity (4 items). The scale rated individual items from 0 to 2 (0=not present, 1=mild, 2=clearly present). The score for attention + organization subscale score ranges from 0-22, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The ANCOVA method was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -1.47 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -1.42 |
Change From Baseline (End of Phase A) in CAARS-O:SV Inattentive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
The CAARS-O:SV is a 30 items scale with 3 subscales DSM-IV Inattentive Symptoms (9 items), DSM-IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). The inattentive symptoms subscale (9 items) is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 27, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change at Week 6 | Change at Week 7 | Change at Week 8 | Change at Week 9 | Change at Week 10 | Change at Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -2.00 | -2.94 | -3.14 | -3.74 | -3.95 | -4.58 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -2.43 | -3.20 | -3.42 | -4.04 | -4.85 | -4.86 |
Change From Baseline (End of Phase A) in CAARS-O:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
The CAARS-O:SV is a 30 items scale with 3 subscales DSM-IV Inattentive Symptoms (9 items), DSM-IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). The hyperactive/impulsive Symptoms Subscale is (9 items) scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 27, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change at Week 6 | Change at Week 7 | Change at Week 8 | Change at Week 9 | Change at Week 10 | Change at Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -1.88 | -2.66 | -3.29 | -3.90 | -3.83 | -4.51 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -2.11 | -2.94 | -3.48 | -4.01 | -4.17 | -4.80 |
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Symptoms Total Score (18 Items) to Each Time Point in Phase B Other Than Week 11
The CAARS-O:SV is a 30 items scale with 3 subscales DSM-IV Inattentive Symptoms (9 items), DSM-IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Weeks 6, 7, 8, 9 and 10
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change at Week 6 | Change at Week 7 | Change at Week 8 | Change at Week 9 | Change at Week 10 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -3.82 | -5.54 | -6.37 | -7.58 | -7.71 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -4.62 | -6.21 | -6.99 | -8.14 | -9.11 |
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Index Score (12 Items) to Each Time Point in Phase B
The CAARS-S:SV is a 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). The ADHD index score (12 items) is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 36, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change at Week 6 | Change at Week 7 | Change at Week 8 | Change at Week 9 | Change at Week 10 | Change at Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -2.06 | -3.47 | -4.01 | -4.32 | -4.65 | -5.60 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -2.20 | -3.38 | -3.80 | -4.78 | -5.23 | -5.94 |
Change From End of Phase A (Week 5 Visit) to End of Phase B (Week 11 Visit) in WRAADDS Hyperactivity + Impulsivity Subscale Score to End of Phase B
WRAADDS is used to measure the severity of symptoms in adults with ADHD. This structured interview consists of 28 items in 7 psychopathologic domains, which were rated by a clinical expert on a 0 to 2-point Likert scale. The psychopathologic 7 domains are inattention (6 items), impulsivity (3 items), and hyperactivity (3 items), disorganization (5 items), temper (3 items), affective lability (4 items), and emotional over-reactivity (4 items). The scale rated individual items from 0 to 2 (0=not present, 1=mild, 2=clearly present). The score for hyperactivity + impulsivity subscale score ranges from 0-12, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The ANCOVA model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -1.27 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -1.01 |
Change From Baseline (End of Phase A) in WRAADDS Temper + Mood Lability + Emotional Over-reactivity Subscale Score to End of Phase B
WRAADDS is used to measure the severity of symptoms in adults with ADHD. This structured interview consists of 28 items in 7 psychopathologic domains, which were rated by a clinical expert on a 0 to 2-point Likert scale. The psychopathologic 7 domains are inattention (6 items), impulsivity (3 items), and hyperactivity (3 items), disorganization (5 items), temper (3 items), affective lability (4 items), and emotional over-reactivity (4 items). The scale rated individual items from 0 to 2 (0=not present, 1=mild, 2=clearly present). The score for temper + mood Lability + emotional over-reactivity subscale score ranges from 0-22, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The ANCOVA model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -1.24 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -1.35 |
Change From Baseline (End of Phase A) in CAARS-S:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
The CAARS-S:SV is a 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). The Hyperactive/Impulsive Symptoms Subscale is (9 items) scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 27, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change at Week 6 | Change at Week 7 | Change at Week 8 | Change at Week 9 | Change at Week 10 | Change at Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -0.91 | -1.38 | -2.09 | -2.18 | -2.21 | -2.86 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -1.06 | -1.88 | -2.20 | -2.87 | -3.33 | -3.31 |
Change From Baseline (End of Phase A) in the SST Proportion of Successful Stops Score as Measured by CANTAB to End of Phase B
SST measures participants ability to inhibit a response. An arrow pointing either left or right is displayed on computer screen. Participant responded to arrow by pressing corresponding button (i.e., left or right) on press pad. If an audio tone is presented when arrow is displayed, participant inhibited his/her response. Proportion of successful stops, and median reaction time on Go trials was measured. The proportion of successful stops is calculated as the number of times that the participant stopped successfully, divided by the total number of stop signals. Observed range for Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant: -0.40 to 0.40 (change from baseline) and for Phase B (Double-blind Randomization Phase): Placebo + Stimulant: -0.38 to 0.38 (change from baseline). Higher scores indicate a positive outcome for proportion of successful stops. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -0.01 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | 0.01 |
Change From Baseline (End of Phase A) in the Spatial Working Memory (SWM) Between Errors 4-8 Boxes Test Score as Measured by Cambridge Neuropsychological Test Automated Battery (CANTAB) to End of Phase B
ADHD was measured with the CANTAB. SWM test was one of the tasks of CANTAB, SWM measured the ability to retain spatial information and to manipulate remembered items in working memory. This test was sensitive measure of executive dysfunction. Participants search for colored tokens hidden inside boxes on screen by touching them. The critical instruction was that once token has been found inside box, no token was hidden inside that box again, so participants must not return to box where a token was found. The key measurement of the SWM task is the SWM Between Errors 4-8 Boxes, which measured the total number of times a participant revisits a box in which a token has previously been found is measured for the 4, 6, and 8-box stages. Total scores ranged from 0-153. A lower score indicated better performance. The ANCOVA model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 0.10 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -0.31 |
Change From Baseline (End of Phase A) in the SWM Strategy 6-8 Boxes Test Score as Measured by CANTAB to End of Phase B
The SWM test assesses the cognitive domain of executive function (high-level thinking and decision making). SWM task was SWM Strategy 6-8 Boxes, in which the total number of distinct boxes used by the participant to begin a new search for a token within the same problem was measured for the 6- and 8-box stages. The SWM strategy index of executive function represented the number of times a participant began a search with a different box. Participant was asked to find tokens in on-screen boxes and move them. Difficulty ranged from 4 to 8 box assessments. Strategy score was the number of unique boxes the participant searched in 6 and 8 box trials. 6 box trial scores ranged from 1 (1 box searched for all 6 tokens) to 6 (6 boxes searched for 6 tokens). 8 box trial score ranged from 1 (1 box searched) to 8 (8 boxes searched for 8 tokens). Total of the 2 trial scores ranged from 2 to 14. A lower score reflects better performance. The ANCOVA method was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 0.15 |
| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -0.12 |
Change From Baseline (End of Phase A) to Weeks 7 and 9 in ISI Total Score
The ISI is self-report instrument that has been validated specifically for measuring the perceived severity of insomnia. The scale was composed of a total of 7 items based on self-report questionnaire based on several indicators assessing the perceived severity of difficulties initiating sleep, staying asleep, and early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Each item was rated on a scale from 0 (none) to 4 (higher score indicating greater impairment/concern). A total score ranging from 0 to 28 was calculated from the sum of the individual item scores, higher scores indicate increased severity of insomnia. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 7 and 9
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change at Week 7 | Change at Week 9 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -0.81 | -0.99 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -0.83 | -1.48 |
Change From Baseline (End of Phase A) in Conners' Adult ADHD Rating Scale-Self-Report: Screening Version (CAARS-S:SV) ADHD Symptoms Total Score (18 Items) to Each Timepoint in Phase B
The CAARS-S:SV is a self-reported 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the Inattentive Symptoms and Hyperactive/Impulsive Symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis. (NCT01074294)
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change at Week 6 | Change at Week 7 | Change at Week 8 | Change at Week 9 | Change at Week 10 | Change at Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | -1.75 | -3.01 | -4.15 | -4.24 | -4.63 | -5.38 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | -2.16 | -3.47 | -4.08 | -5.23 | -6.11 | -6.33 |
Percentage of Participants With CGI-I Response Rate in Phase B
Response was defined as a CGI-I score of 1 or 2 (very much improved or much improved). The CGI-I permits a global evaluation of the participant's improvement over time. The CGI-I is a 8-point scale ranging from 0 to 7 where 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse and 7=very much worse. The Cochran-Mantel-Haenszel model was used for analysis. (NCT01074294)
Timeframe: Weeks 6, 7, 8, 9, 10 and 11
| Intervention | percentage of participants (Number) |
|---|
| Week 6 | Week 7 | Week 8 | Week 9 | Week 10 | Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 18.3 | 23.5 | 31.4 | 37.9 | 40.5 | 44.4 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | 15.4 | 17.9 | 30.8 | 41.0 | 39.7 | 44.9 |
Mean CGI-I Score at Each Timepoint in Phase B
The CGI-I permits a global evaluation of the participant's improvement over time. The CGI-I is a 8-point scale ranging from 0 to 7 where 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse and 7=very much worse. The CGI-I is completed by the clinician and assesses the participant's improvement relative to the symptoms at Baseline. The Cochran-Mantel-Haenszel model was used for analysis. (NCT01074294)
Timeframe: Weeks 6, 7, 8, 9, 10 and 11
| Intervention | score on a scale (Mean) |
|---|
| Week 6 | Week 7 | Week 8 | Week 9 | Week 10 | Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 3.19 | 3.04 | 2.93 | 2.82 | 2.80 | 2.68 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | 3.12 | 3.08 | 2.88 | 2.81 | 2.76 | 2.69 |
Percentage of Participants With CAARS-O:SV ADHD Symptoms Remission Rate in Phase B
Remission was defined as CAARS-O:SV ADHD Symptoms Total Score (18 items) of ≤ 18 and a ≥ 30% reduction in CAARS-O:SV ADHD Symptoms Total Score (18 items) from end of Phase A (Week 5 visit). An 18-item ADHD Symptoms Total Score consisted of the combined score for the Inattentive Symptoms and Hyperactive/Impulsive Symptoms subscales. The CAARS-O:SV was designed to measure a cross-section of ADHD-related symptoms and behaviors in adults using observer and self-report scales. Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for a total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. The Cochran-Mantel-Haenszel model was used for analysis. (NCT01074294)
Timeframe: Weeks 6, 7, 8, 9, 10 and 11
| Intervention | percentage of participants (Number) |
|---|
| Week 6 | Week 7 | Week 8 | Week 9 | Week 10 | Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 7.19 | 12.4 | 19.0 | 20.9 | 25.5 | 27.5 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | 6.41 | 12.8 | 19.2 | 23.1 | 28.2 | 33.3 |
Percentage of Participants With CAARS-O:SV ADHD Symptoms Response Rate in Phase B
Response was defined as ≥ 30% reduction in CAARS-O:SV ADHD Symptoms Total Score (18 items) from end of Phase A (Week 5 visit). An 18-item ADHD Symptoms Total Score consisted of the combined score for the Inattentive Symptoms and Hyperactive/Impulsive Symptoms subscales. The CAARS-O:SV was designed to measure a cross-section of ADHD-related symptoms and behaviors in adults using observer and self-report scales. Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for a total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. (NCT01074294)
Timeframe: Weeks 6, 7, 8, 9, 10 and 11
| Intervention | percentage of participants (Number) |
|---|
| Week 6 | Week 7 | Week 8 | Week 9 | Week 10 | Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 15.0 | 24.2 | 28.8 | 35.9 | 37.9 | 45.1 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | 12.8 | 24.4 | 33.3 | 41.0 | 44.9 | 50.0 |
Percentage of Participants With CAARS-S:SV ADHD Symptoms Remission Rate in Phase B
Remission was defined as CAARS-S:SV ADHD Symptoms Total Score (18 items) of ≤ 18 and a ≥ 30% reduction in CAARS-S:SV ADHD Symptoms Total Score (18 items) from end of Phase A (Week 5 visit). The CAARS-S:SV is a 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the Inattentive Symptoms and Hyperactive/Impulsive Symptoms subscales is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. The Cochran-Mantel-Haenszel model was used for analysis. (NCT01074294)
Timeframe: Weeks 6, 7, 8, 9, 10 and 11
| Intervention | percentage of participants (Number) |
|---|
| Week 6 | Week 7 | Week 8 | Week 9 | Week 10 | Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 8.50 | 12.4 | 15.7 | 20.9 | 20.9 | 24.2 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | 7.69 | 12.8 | 15.4 | 20.5 | 19.2 | 25.6 |
Percentage of Participants With CAARS-S:SV ADHD Symptoms Response Rate in Phase B
Response was defined as ≥ 30% reduction in CAARS-S:SV ADHD Symptoms Total Score (18 items) from end of Phase A (Week 5 visit). The CAARS-S:SV is a 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the Inattentive Symptoms and Hyperactive/Impulsive Symptoms subscales is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. The Cochran-Mantel-Haenszel model was used for analysis. (NCT01074294)
Timeframe: Weeks 6, 7, 8, 9, 10 and 11
| Intervention | percentage of participants (Number) |
|---|
| Week 6 | Week 7 | Week 8 | Week 9 | Week 10 | Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 11.8 | 18.3 | 21.6 | 29.4 | 25.5 | 31.4 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | 12.8 | 15.4 | 21.8 | 29.5 | 32.1 | 37.2 |
Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B
The ISI is self-report instrument that has been validated specifically for measuring the perceived severity of insomnia. The scale was composed of a total of 7 items based on self-report questionnaire based on several indicators assessing the perceived severity. difficulties initiating sleep, staying asleep, and early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Each item was rated on a scale from 0 (none) to 4 (higher score indicating greater impairment/concern). A negative change from Baseline indicates improvement. The Cochran-Mantel-Haenszel model was used for analysis. (NCT01074294)
Timeframe: Baseline [(end of Phase A (Week 5)] to Weeks 7, 9 and 11
| Intervention | percentage of participants (Number) |
|---|
| Difficulty Falling Asleep: Week 7 | Difficulty Falling Asleep: Week 9 | Difficulty Falling Asleep: Week 11 | Difficulty Staying Asleep: Week 7 | Difficulty Staying Asleep: Week 9 | Difficulty Staying Asleep: Week 11 | Waking Up Too Early: Week 7 | Waking Up Too Early: Week 9 | Waking Up Too Early: Week 11 |
|---|
| Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant | 33.6 | 33.3 | 35.3 | 26.8 | 25.3 | 24.7 | 28.2 | 30.7 | 29.3 |
,| Phase B (Double-blind Randomization Phase): Placebo + Stimulant | 32.4 | 37.7 | 39.0 | 35.1 | 33.8 | 37.7 | 25.7 | 26.0 | 28.6 |
Clinical Global Impression- Improvement Scale (CGI-I) Score at Week 6
The participant's overall improvement was rated using the CGI-I. The rater or study physician rated the participant's total improvement whether or not it was due entirely to drug treatment. All responses were compared with the participant's condition at screening/baseline. Response choices were: 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. (NCT01396421)
Timeframe: Week 6
| Intervention | Units on a scale (Mean) |
|---|
| Brexpiprazole 4mg | 2.94 |
| Brexpiprazole 2mg | 2.94 |
| Brexpiprazole 0.25mg | 3.37 |
| Placebo | 3.48 |
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score.
"The severity of illness was rated using the CGI-S. To perform this assessment, the rater or study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0=not assessed; 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participant." (NCT01396421)
Timeframe: Baseline to Week 1, 2, 3, 4 and 5
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 1 | Week 2 | Week 3 | Week 4 | Week 5 |
|---|
| Brexpiprazole 0.25mg | -0.11 | -0.18 | -0.33 | -0.58 | -0.73 |
,| Brexpiprazole 2mg | -0.16 | -0.43 | -0.60 | -0.73 | -1.03 |
,| Brexpiprazole 4mg | -0.16 | -0.46 | -0.72 | -0.96 | -1.08 |
,| Placebo | -0.14 | -0.30 | -0.51 | -0.54 | -0.69 |
Mean Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score.
"The severity of illness was rated using the CGI-S which is the key secondary endpoint. To perform this assessment, the rater or study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0=not assessed; 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participant." (NCT01396421)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 4 mg | -1.20 |
| Brexpiprazole 2 mg | -1.15 |
| Brexpiprazole 0.25 mg | -0.85 |
| Placebo | -0.82 |
Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score
The PEC consists of 5 PANSS items (excitement [P4], hostility [P7], tension [G4], uncooperativeness [G8], and poor impulse control [G14]). Each rated on a scale of 1 (absent) to 7 (extreme). The PEC for participants was calculated as the sum of the rating assigned to each of the 5 items, and ranged from 5 to 35 with a higher score indicating greater severity of symptoms. (NCT01396421)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 4mg | -2.75 |
| Brexpiprazole 2mg | -2.87 |
| Brexpiprazole 0.25mg | -1.99 |
| Placebo | -1.64 |
Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score
For each symptom construct of the PANSS Negative Subscale, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The symptom constructs were as follows: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale Score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. (NCT01396421)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 4mg | -3.65 |
| Brexpiprazole 2mg | -4.02 |
| Brexpiprazole 0.25mg | -3.31 |
| Placebo | -2.24 |
Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score
For each symptom construct of the PANSS Positive Subscale, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The symptom constructs were as follows: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale Score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. (NCT01396421)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 4mg | -6.78 |
| Brexpiprazole 2mg | -6.57 |
| Brexpiprazole 0.25mg | -5.46 |
| Placebo | -4.35 |
Response Rate at Week 6
Response rate was defined as improvement in mean change of ≥30% from baseline in PANSS Total Score at Week 6 or CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6. (NCT01396421)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|
| Brexpiprazole 4mg | 46.07 |
| Brexpiprazole 2mg | 47.78 |
| Brexpiprazole 0.25mg | 39.08 |
| Placebo | 30.34 |
Mean Change From Baseline to Week 6 Positive and Negative Syndrome Scale (PANSS) Total Score.
The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). (NCT01396421)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 4mg | -19.65 |
| Brexpiprazole 2 mg | -20.73 |
| Brexpiprazole 0.25 mg | -14.90 |
| Placebo | -12.01 |
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score.
The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). (NCT01396421)
Timeframe: Baseline to Week 1, 2, 3, 4, 5
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 1 | Week 2 | Week 3 | Week 4 | Week 5 |
|---|
| Brexpiprazole 0.25mg | -2.52 | -3.28 | -5.71 | -8.86 | -11.87 |
,| Brexpiprazole 2mg | -4.87 | -8.86 | -11.08 | -14.06 | -17.90 |
,| Brexpiprazole 4mg | -4.38 | -9.51 | -12.78 | -16.50 | -18.61 |
,| Placebo | -2.87 | -5.11 | -7.64 | -8.89 | -10.75 |
Change From Baseline to Week 6 in PANSS Marder Anxiety Depression Score
The PANSS Marder Factor score - Anxiety/Depression Score consists of 4 PANSS items (anxiety [G2], guilt feelings [G3], tension [G4], depression [G6]). The PANSS Marder Factor score - Anxiety/Depression Score for participants was calculated as the sum of the rating assigned to each of the 4 items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. (NCT01396421)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 4mg | -3.40 |
| Brexpiprazole 2mg | -3.70 |
| Brexpiprazole 0.25mg | -3.27 |
| Placebo | -3.05 |
Change From Baseline to Week 6 in PANSS Marder Disorganised Thought Score
The PANSS Marder Factor score -Disorganized Thought Score consists of 7 PANSS items (conceptual disorganization [P2], difficulty in abstract thinking [N5], mannerisms and posturing [G5], disorientation [G10], poor attention [G11], disturbance of violation [G13], preoccupation [G15]). The PANSS Marder Factor score - Disorganized Thought Score for participants was calculated as the sum of the rating assigned to each of the 7 items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. (NCT01396421)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 4mg | -3.72 |
| Brexpiprazole 2mg | -3.94 |
| Brexpiprazole 0.25mg | -2.69 |
| Placebo | -1.97 |
Change From Baseline to Week 6 in PANSS Marder Factor Score - Negative Symptoms Score
The PANSS Marder Factor score - Negative Symptoms Score consists of 7 PANSS items (blunted effect [N1], emotional withdrawal [N2], poor rapport [N3], passive/apathetic social withdrawal [N4], lack of spontaneity and conversation flow [N6], motor retardation [G7], active social avoidance [G16]). The PANSS Marder Factor score - Negative Symptoms Score for participants was calculated as the sum of the rating assigned to each of the 7 items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. (NCT01396421)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 4mg | -4.10 |
| Brexpiprazole 2mg | -4.48 |
| Brexpiprazole 0.25mg | -3.66 |
| Placebo | -2.80 |
Change From Baseline to Week 6 in PANSS Marder Factor Score - Positive Symptoms Score
The PANSS Marder Factor score - Positive Symptoms Score consists of 8 PANSS items (delusions [P1], hallucinatory behaviour [P3], grandiosity [P5], suspiciousness [P6], stereotyped thinking [N7], somatic concern [G1], unusual thought content [G9], lack of judgment and insight [G10]. Each was rated on a scale of 1 (absent) to 7 (extreme). The PANSS Marder Factor score - Positive Symptoms Score for participants was calculated as the sum of the rating assigned to each of the 8 items, and ranged from 8 to 42 with a higher score indicating greater severity of symptoms. (NCT01396421)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 4mg | -7.23 |
| Brexpiprazole 2mg | -7.37 |
| Brexpiprazole 0.25mg | -5.78 |
| Placebo | -4.89 |
Change From Baseline to Week 6 in PANSS Marder Uncontrolled Hostility/Excitement Score
The PANSS Marder Factor score - Uncontrolled Hostility/Excitement Score consists of 4 PANSS items (excitement [P4], hostility [P7], uncooperativeness [G8], poor impulse control [G14]). The PANSS Marder Factor score - Uncontrolled Hostility/Excitement Score for participants was calculated as the sum of the rating assigned to each of the 4 items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. (NCT01396421)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 4mg | -1.90 |
| Brexpiprazole 2mg | -1.91 |
| Brexpiprazole 0.25mg | -1.15 |
| Placebo | -0.82 |
Discontinuation Rate for Lack of Efficacy at Week 6
(NCT01396421)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|
| Brexpiprazole 4mg | 3.93 |
| Brexpiprazole 2mg | 9.44 |
| Brexpiprazole 0.25mg | 8.05 |
| Placebo | 10.11 |
Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.
"The primary efficacy variable was time to impending relapse from randomization, as assessed by Clinical Global Impression of Improvement (CGI-I) score ≥5, Positive and Negative Syndrome Scale (PANSS) scores for hostility or uncooperativeness ≥5, or ≥20% increase in PANSS Total Score. Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score >4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content).OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of yes to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.The measure type, number is Hazard Ratio." (NCT01668797)
Timeframe: From randomization to time of exacerbation of psychotic symptoms/impending relapse - up to 52 weeks
| Intervention | Days (Number) |
|---|
| Brexpiprazole | 0.292 |
| Placebo | 3.420 |
Percentage of Participants Who Discontinued Due to All Causes
Analysis of the percentage of participants who discontinued due to all causes was based on all participants who have been randomized and taken one dose of IMP in the Double-blind Maintenance phase. The trial was completed by sponsor when efficacy was demonstrated at the first pre-specified interim analysis (45 impending relapse events) performed by an independent (unblinded) statistician. (NCT01668797)
Timeframe: Baseline to Week 52
| Intervention | Percentage of particpants (Number) |
|---|
| Brexpiprazole | 34.38 |
| Placebo | 54.81 |
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance Phase
"Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score > 4 with an absolute increase of ≥ 2 on that specific item or an increase on any of the following individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual though content) to a score of >4 and an absolute increase of ≥ 4 on the combined 4 PANSS items. OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Current suicidal behavior as assessed by the C-SSRS (ie, an answer of yes to any of the questions on the suicidal behavior section of the C-SSRS 5) Violent or aggressive behavior resulting in clinically significant self-injury to another person, or property damage." (NCT01668797)
Timeframe: Baseline and Week 52/Early Termination
| Intervention | percentage of participants (Number) |
|---|
| Brexpiprazole | 13.54 |
| Placebo | 38.46 |
Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis
PANSS consisted of three subscales: a total of 30 symptom constructs. For each construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | 0.30 | 0.38 | 0.49 | 0.97 | 0.99 |
,| Placebo | 1.25 | 2.24 | 3.23 | 3.91 | 4.17 |
Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis
PANSS consisted of three subscales: a total of 30 symptom constructs. For each construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | 0.17 | -0.06 | -0.84 | -0.97 | -1.21 |
,| Placebo | 1.28 | 1.81 | 0.72 | 0.91 | 1.50 |
Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase
"Participants were assessed for stability using the following criteria:1) Outpatient status AND 2) Positive and Negative Syndrome Scale (PANSS) Total Score ≤ 70 AND 3) A score of ≤ 4 (moderate) on each of the following PANSS items (possible scores of 1 to 7 for each item): conceptual disorganization, suspiciousness hallucinatory behavior, unusual thought content, AND 4) Clinical Global Impression - Severity of Illness scale(CGI-S) score ≤ 4 (moderately ill) AND 5) No current suicidal behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS), defined as the following: An answer of no to each question on the Suicidal Behavior section of the C-SSRS AND an answer of no to Questions 4 and 5 on the Suicidal Ideation section of the C-SSRS, if completed, AND 6) No evidence of aggressive or violent behavior resulting in clinically significant self-injury, injury to another person, property damage." (NCT01668797)
Timeframe: Weeks 6, 12, 24, 36 and 52
| Intervention | percentage of participants (Number) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) | Last Visit (N= 96, 104) |
|---|
| Brexpiprazole | 92.59 | 93.15 | 96.00 | 93.94 | 86.67 | 79.17 |
,| Placebo | 86.90 | 86.76 | 94.44 | 83.33 | 88.89 | 56.73 |
Mean Change From Baseline in PSP Scale Score - LOCF Analysis
The PSP is a validated clinician-rated scale that measures personal and social functioning in four domains: socially useful activities (e.g., work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment in each of these domains is rated as absent, mild, manifest, marked, severe, or very severe. These ratings are then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment to determine the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 are considered to have mild functional difficulty. Scores of 31 to 70 represent manifest disabilities of various degrees and ratings of 1 to 30 indicate minimal functioning that requires intense support and/or supervision.The PSP score ranges from 0 to 100, with higher scores indicating higher levels of social functioning. (NCT01668797)
Timeframe: Baseline and Weeks 24 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 24 | Week 52 |
|---|
| Brexpiprazole | 15.20 | 15.06 |
,| Placebo | 11.41 | 10.31 |
Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | 0.79 | 0.84 | -1.88 | -2.71 | 0.61 |
,| Placebo | 4.09 | 6.15 | 2.89 | 3.33 | 6.92 |
Mean Change From Baseline in PEC Score - LOCF Analysis
The PEC score consisted of five PANSS items: excitement (P4), hostility (P7), tension (G4), uncooperativeness (G8), and poor impulse control (G14). Each of the items were rated on a scale of 1 (absent) to 7 (extreme). The PEC scores ranged from 5 (not present) to 35 (extremely severe). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | 0.38 | 0.73 | 0.78 | 0.89 | 0.82 |
,| Placebo | 0.81 | 1.36 | 1.86 | 2.23 | 2.35 |
Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | 0.51 | 1.55 | 1.58 | 2.49 | 3.25 |
,| Placebo | 3.56 | 6.60 | 9.17 | 10.51 | 11.20 |
Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS negative subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | -0.04 | -0.22 | -0.78 | -1.03 | 1.30 |
,| Placebo | 0.65 | 0.55 | 0.18 | 0.02 | 0.87 |
Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS negative subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | -0.12 | -0.17 | -0.08 | -0.14 | 0.39 |
,| Placebo | 0.63 | 1.06 | 1.47 | 1.44 | 1.63 |
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis
Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | 0.19 | 0.33 | -0.26 | -0.13 | -0.20 |
,| Placebo | 0.55 | 0.82 | 0.81 | 0.94 | 0.94 |
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis
Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | 0.32 | 0.52 | 0.50 | 0.57 | 0.49 |
,| Placebo | 0.65 | 0.94 | 1.31 | 1.63 | 1.75 |
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis
Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | -0.10 | -0.18 | -0.82 | -1.35 | -1.62 |
,| Placebo | 1.24 | 1.83 | 0.77 | 0.93 | 1.78 |
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis
Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | 0.05 | 0.10 | 0.25 | 0.60 | 0.58 |
,| Placebo | 1.13 | 2.03 | 3.08 | 3.69 | 4.02 |
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis
Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | 0.02 | -0.01 | -0.71 | -0.80 | 1.37 |
,| Placebo | 0.68 | 0.80 | 0.46 | 0.70 | 1.06 |
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis
Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | -0.24 | -0.15 | -0.09 | -0.07 | 0.34 |
,| Placebo | 0.61 | 1.09 | 1.50 | 1.56 | 1.57 |
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis
Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | -0.18 | -0.44 | -1.26 | -1.31 | -0.37 |
,| Placebo | 0.32 | 0.69 | 0.27 | 0.17 | -0.30 |
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis
Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | -0.32 | -0.19 | -0.29 | 0.00 | 0.29 |
,| Placebo | 0.33 | 1.19 | 1.76 | 1.95 | 1.97 |
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis
Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The anxiety/depression factor score is the sum of score from the 4 items on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | 0.19 | 0.54 | 0.61 | 0.46 | 0.04 |
,| Placebo | 0.66 | 0.78 | 0.58 | 0.71 | 0.28 |
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis
Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The anxiety/depression factor score is the sum of score from the 4 items on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | 0.19 | 0.86 | 1.07 | 1.09 | 1.17 |
,| Placebo | 0.85 | 1.41 | 1.64 | 1.79 | 1.88 |
Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis
The PEC score consisted of five PANSS items: excitement (P4), hostility (P7), tension (G4), uncooperativeness (G8), and poor impulse control (G14). Each of the items were rated on a scale of 1 (absent) to 7 (extreme). The PEC scores ranged from 5 (not present) to 35 (extremely severe). (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | 0.32 | 0.50 | -0.06 | 0.10 | -0.04 |
,| Placebo | 0.74 | 1.16 | 0.45 | 1.25 | 1.00 |
Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis
The GAF is a clinician-rated scale that assesses the participant's psychological, social, and occupational functioning on a hypothetical continuum of mental health-illness using a scale that ranges from 1 to 100 score, where lower values indicate worst outcome. From among 10 descriptive anchors, investigators will choose the anchor which is the most representative of the participant's level of functioning at the time of the assessment and will assign a single score within the point range given for the selected anchor. (NCT01668797)
Timeframe: Baseline and Weeks 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | 1.59 | 3.74 | 4.71 | 5.72 |
,| Placebo | -0.03 | 1.09 | 0.21 | -0.16 |
Mean Change From Baseline in GAF Scale Score - LOCF Analysis
The GAF is a clinician-rated scale that assesses the participant's psychological, social, and occupational functioning on a hypothetical continuum of mental health-illness using a scale that ranges from 1 to 100 score, where lower values indicate worst outcome. From among 10 descriptive anchors, investigators will choose the anchor which is the most representative of the participant's level of functioning at the time of the assessment and will assign a single score within the point range given for the selected anchor. (NCT01668797)
Timeframe: Baseline and Weeks 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | 0.44 | 0.85 | 0.97 | 0.55 |
,| Placebo | -3.44 | -4.51 | -5.84 | -6.01 |
Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis
The rater or investigator would rate the participant's total improvement whether or not it is due entirely to study treatment. During Phase B, responses were compared to the participant's condition at Baseline of Phase B (for participants who entered Phase B directly after screening) or to the End of Phase A visit (for participants who participated in Phase A). During Phase C, responses were compared to the participant's condition at the End of Phase B visit. Response choices include: 0 = Not assessed, 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, and 7 = Very much worse. (NCT01668797)
Timeframe: Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | 3.68 | 3.66 | 3.67 | 3.71 | 3.77 |
,| Placebo | 4.00 | 4.10 | 4.30 | 4.39 | 4.40 |
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis
"The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants." (NCT01668797)
Timeframe: Baseline, Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 (N= 81, 84) | Week 12 (N= 73, 68) | Week 24 (N= 50, 36) | Week 36 (N= 33, 24) | Week 52 (N= 15, 9) |
|---|
| Brexpiprazole | -0.01 | -0.01 | -0.16 | -0.31 | -0.23 |
,| Placebo | 0.26 | 0.37 | 0.21 | 0.25 | 0.28 |
Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis
"The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants." (NCT01668797)
Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Week 6 | Week 12 | Week 24 | Week 36 | Week 52 |
|---|
| Brexpiprazole | -0.08 | -0.04 | -0.03 | -0.00 | 0.02 |
,| Placebo | 0.17 | 0.32 | 0.47 | 0.56 | 0.55 |
Mean Change From Baseline to Study Completion in Simpson-Angus Scale (SAS) Total Score
EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The SAS is a rating scale used to measure EPS. The SAS scale consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40. (NCT01670279)
Timeframe: End of Titration, Day 15, Day 29, Early Termination and Last visit
| Intervention | Units on a scale (Mean) |
|---|
| End of Titration (N= 6, 6, 4) | Day 15 (N= 0, 5, 2) | Day 29 (N=6, 0, 2) | Early Termination (N= 0, 1, 1) | Last visit (N= 6, 6, 5) |
|---|
| Brexpiprazole-Cohort 1 | -0.3 | NA | -0.3 | NA | -0.2 |
,| Brexpiprazole-Cohort 2 | -0.5 | 0.2 | NA | -1.0 | 0.0 |
,| Placebo | -1.0 | -1.5 | 0.0 | 0.0 | -0.6 |
Number of AEs Reported.
The AEs were one of the primary parameters to measure the safety and tolerability of individual participants. The AEs were captured for all participants from the time the ICF was signed until the end of the trial. AEs were measured throughout the 14-day titration and 28-day fixed dose phase until follow-up (30 [±2] days after last dose of study medication). (NCT01670279)
Timeframe: Throughout the study, up to 119 days
| Intervention | Events (Number) |
|---|
| Adverse events | Treatment emergent adverse events (TEAEs) | Serious adverse events |
|---|
| Brexpiprazole-Cohort 1 | 12 | 6 | 0 |
,| Brexpiprazole-Cohort 2 | 33 | 6 | 0 |
,| Placebo | 5 | 3 | 0 |
Incidence of Physical Examination Evaluation of Potential Clinical Significance
The physical examination evaluation was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in the following body systems: head, ears, eyes, nose, and throat; thorax; abdomen; urogenital; extremities; neurological; and skin and mucosae. (NCT01670279)
Timeframe: Physical examination was performed at Screening, check-in, and discharge
| Intervention | Participants (Number) |
|---|
| Brexpiprazole-Cohort 1 | 0 |
| Brexpiprazole-Cohort 2 | 0 |
| Placebo | 0 |
Number of Participants Who Tolerated Brexpiprazole
Safety and tolerability of brexpiprazole was noted to be primary outcome measure. Brexpiprazole was judged to be tolerated if at least 6 out of 8 (75%) of the participants in a test cohort tolerated the dose after 14 days of QD dosing at the end of the fixed dose phase based on the blinded data. Dose toleration was defined as follows: during the course of the trial, the participants did not experience any moderate or severe adverse events (AEs) or potentially clinically relevant changes from Baseline in laboratory values, vital signs, electrocardiogram (ECG) tracings, Columbia-Suicide Severity Rating Scale (C-SSRS), or extrapyramidal symptom (EPS) ratings, which were assessed as possibly related to the study drug, and would have warranted a dose decrease or discontinuation of the study drug. The safety and tolerability of brexpiprazole was defined by parameters: AEs, laboratory values, vital signs, ECG, C-SSRS, or EPS ratings, the results of each of the parameters reported separately. (NCT01670279)
Timeframe: 45 Days
| Intervention | participants (Number) |
|---|
| Brexpiprazole-Cohort 1 | 6 |
| Brexpiprazole-Cohort 2 | 7 |
| Placebo | 5 |
Change From Baseline to Study Completion in C-SSRS Score.
The C-SSRS was one of the primary parameters to measure the safety and tolerability of individual participants. Suicidality was monitored during the trial using the C-SSRS. This scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicide events and suicidal ideation and a post-baseline evaluation that focuses on suicidality since the last trial visit. (NCT01670279)
Timeframe: Baseline, End of Titration, Fixed dose Day 14 and 28, Day 15 and 29, Early Termination, Last Visit
| Intervention | Participants (Number) |
|---|
| Suicidality | Suicidal behaviour | Suicidal ideation |
|---|
| Brexpiprazole-Cohort 1 | 0 | 0 | 0 |
,| Brexpiprazole-Cohort 2 | 0 | 0 | 0 |
,| Placebo | 0 | 0 | 0 |
Incidence of ECG Evaluations of Potential Clinical Significance
The measurement of ECG was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, and QTcF that were identified based on pre-defined criteria. (NCT01670279)
Timeframe: Titratrion Day 1 and 7, Fixed dose Day 1, 14, 28, Early Termination
| Intervention | Participants (Number) |
|---|
| Supraventricular premature beat | Ventricular premature beat | Left bundle-branch block | Myocardial ischemia | Symmetrical T-wave inversions | Increase in QTcB | Increase in QTcF |
|---|
| Brexpiprazole-Cohort 1 | 0 | 3 | 0 | 1 | 1 | 1 | 1 |
,| Brexpiprazole-Cohort 2 | 2 | 0 | 0 | 0 | 1 | 3 | 2 |
,| Placebo | 1 | 1 | 1 | 0 | 0 | 2 | 2 |
Incidence of Laboratory Values of Potential Clinical Significance
The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria. (NCT01670279)
Timeframe: Titration Day 7, Fixed dose Day 14 and 28 and Last Visit
| Intervention | Participants (Number) |
|---|
| Cholesterol, fasting | Glucose | LDL direct, fasting | Triglycerides, fasting | Uric acid | Hematocrit | Prolactin |
|---|
| Brexpiprazole-Cohort 1 | 0 | 0 | 0 | 2 | 0 | 0 | 2 |
,| Brexpiprazole-Cohort 2 | 1 | 0 | 0 | 1 | 0 | 2 | 0 |
,| Placebo | 1 | 1 | 1 | 3 | 1 | 1 | 0 |
Incidence of Vital Signs of Potential Clinical Significance
The vital signs were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in heart rate, systolic and diastolic blood pressure, respiratory rate and weight that were identified based on pre-defined criteria. (NCT01670279)
Timeframe: Baseline, Titration Day 1, 2, 7, 8, Fixed Days 1, 2, 14, 15, 28, 29, Early Termination and Last Visit.
| Intervention | Participants (Number) |
|---|
| Weight increase | Supine hypotension, decrease |
|---|
| Brexpiprazole-Cohort 1 | 2 | 1 |
,| Brexpiprazole-Cohort 2 | 0 | 0 |
,| Placebo | 0 | 0 |
Mean Change From Baseline to Study Completion in Abnormal Involuntary Movement Scale (AIMS) Rating Score.
EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The AIMS Scale was an EPS rating scale. The AIMS is a 12 item scale. The first 10 items are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28. (NCT01670279)
Timeframe: End of Titration, Day 15, Day 29, Early Termination and Last visit
| Intervention | Units on a scale (Mean) |
|---|
| End of Titration (N= 6, 6, 4) | Day 15 (N= 0, 5, 2) | Day 29 (N= 6, 0, 2) | Early Termination (N= 0, 1, 1) | Last Visit (N= 6, 6, 5) |
|---|
| Brexpiprazole-Cohort 1 | 0.0 | NA | 0.0 | NA | 0.0 |
,| Brexpiprazole-Cohort 2 | 0.2 | 0.0 | NA | 0.0 | 0.0 |
,| Placebo | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
Mean Change From Baseline to Study Completion in Barnes Akathisia Global Score
EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The Barnes Akathisia Rating Scale was an EPS rating scale. The Barnes Akathisia Rating Scale was used to assess the presence and severity of akathisia. This scale consists of 4 items. Only the 4th item, the Global Clinical Assessment of Akathisia, was evaluated in this trial. This item is rated on a 6 point scale, with 0 being best (absent) and 5 being worst (severe akathisia). (NCT01670279)
Timeframe: End of Titration, Day 15, Day 29, Early Termination and Last visit
| Intervention | Units on a scale (Mean) |
|---|
| End of Titration (N= 6, 6, 4) | Day 15 (N= 0, 5, 2) | Day 29 (N= 6, 0, 2) | Early Termination (N= 0, 1, 1) | Last visit (N= 6, 6, 5) |
|---|
| Brexpiprazole-Cohort 1 | -0.2 | NA | 0.0 | NA | 0.0 |
,| Brexpiprazole-Cohort 2 | 0.0 | 0.0 | NA | 0.0 | 0.0 |
,| Placebo | -0.5 | -0.5 | -0.5 | 0.0 | -0.4 |
CGI-I Response Rate
CGI-I Response rate, where response was defined as a CGI-I score of 1 or 2 (very much improved or much improved), during double-blind randomized Phase B treatment. (NCT01727726)
Timeframe: Phase B week 6 (14/16 weeks after randomization).
| Intervention | Participants (Count of Participants) |
|---|
| Brexpiprazole + ADT | 100 |
| Seroquel XR + ADT | 48 |
| Placebo + ADT | 79 |
Sheehan Disability Scale (SDS) Individual Item Scores.
To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale (a self rated questionnaire) was used for measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains (work/school work, social life/leisure activities and family life/home responsibilities). All domains were rated on a score scale ranged from 0 (no impairment) to 10 (most severe). Score of 5 and above indicated significant functional impairment. A total score was addition of the 3 individual scores and the total score ranged from 0 (no impairment) to 30 (most severe). (NCT01727726)
Timeframe: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Work/School Score | Social Life Score | Family Life Score |
|---|
| Brexpiprazole + ADT | -0.59 | -1.03 | -1.02 |
,| Placebo + ADT | -0.74 | -0.70 | -0.67 |
,| Seroquel XR + ADT | -0.22 | -0.26 | -0.34 |
MADRS Response at Week 6
MADRS Response Rate, where response was defined as 50% reduction in MADRS Total Score, during double-blind randomized Phase B treatment. (NCT01727726)
Timeframe: Phase B week 6 (14/16 weeks after randomization).
| Intervention | Participants (Count of Participants) |
|---|
| Brexpiprazole + ADT | 20 |
| Seroquel XR + ADT | 8 |
| Placebo + ADT | 14 |
Montgomery Asberg Depression Rating Scale (MADRS)
To determine the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy by assessment of MADRS total score. The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression. (NCT01727726)
Timeframe: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole + ADT | -6.04 |
| Seroquel XR + ADT | -4.86 |
| Placebo + ADT | -4.57 |
Number of Participants With MADRS
MADRS Remission Rate, where remission was defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score, for every trial week visit during double-blind randomized Phase B treatment. (NCT01727726)
Timeframe: Phase B week 6 (14/16 weeks after randomization).
| Intervention | Participants (Count of Participants) |
|---|
| Brexpiprazole + ADT | 13 |
| Seroquel XR + ADT | 2 |
| Placebo + ADT | 9 |
Sheehan Disability Scale (SDS)
To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale is a measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains ( work/social life/family life/home responsibilities). The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. Scores of 5 and above are associated with significant functional impairment. Additionally, SDS included 2 questions related to productivity losses due to the psychiatric symptoms and impairment. (NCT01727726)
Timeframe: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole + ADT | -0.97 |
| Seroquel XR + ADT | -0.32 |
| Placebo + ADT | -0.74 |
Change From End of Phase A in MADRS Total Score for Trial Week 2 and Week 4.
Change from end of Phase A in MADRS Total Score. The MADRS was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression. (NCT01727726)
Timeframe: Change from baseline to week 2 and week 4 in Phase B (week 10/12 and week 12/14)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Phase B Week 2 | Phase B Week 4 |
|---|
| Brexpiprazole + ADT | -2.57 | -4.39 |
,| Placebo + ADT | -1.04 | -3.22 |
,| Seroquel XR + ADT | -2.26 | -3.30 |
Clinical Global Impression Score
Mean change from end of Phase A in Clinical Global Impression - Severity of Illness scale (CGI-S) score and Improvement scale (CGI-I) during double-blind randomized Phase B treatment. CGI-S score assessed how mentally ill the patient was at that time. CGI-S score is calculated from 0 to 7 (0 indicates not assessed 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and7 indicated among the most extremely ill patient). CGI-I score is compared to his/her condition at baseline, how much has the patient changed. CGI-I score is calculated from 0 to 7 (0 indicates not assessed and 7 indicates very much worse). (NCT01727726)
Timeframe: From randomization to Phase B week 6 (14/16 weeks after randomization).
| Intervention | Mean score (Mean) |
|---|
| CGI-Severity of Illness Scale | CGI-Improvement Scale Score |
|---|
| Brexpiprazole + ADT | 3.98 | 2.55 |
,| Placebo + ADT | 4.02 | 2.74 |
,| Seroquel XR + ADT | 4.07 | 2.71 |
Number of Participants With Adverse Events
To evaluate the safety and tolerability of brexpiprazole (flexible dose) as adjunctive therapy to ADT in the proposed subject population with MDD as AE variables. (NCT01727726)
Timeframe: From screening (Day -28 to Day-1) upto post treatment follow-up.
| Intervention | Participants (Count of Participants) |
|---|
| Death | Serious TEAE | Discontinuation due to TEAE | Any TEAE |
|---|
| Brexpiprazole + ADT | 0 | 0 | 2 | 100 |
,| Placebo + ADT | 0 | 1 | 1 | 107 |
,| Seroquel XR + ADT | 0 | 1 | 4 | 58 |
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: negative symptoms is calculated from 7 items (for example: blunted affect, emotional withdrawal and motor retardation). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -3.6 |
| Brexpiprazole | -4.3 |
| Quetiapine Extended Release | -4.8 |
Change From Baseline to Week 6 in PANSS Positive Subscale Score
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Positive Subscale score is calculated from 7 items (for example: delusions, conceptual disorganization and hallucinatory behaviour). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -5.4 |
| Brexpiprazole | -7.0 |
| Quetiapine Extended Release | -8.1 |
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: uncontrolled hostility/excitement is calculated from 4 items (for example: excitement, hostility, and uncooperativeness).Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -1.8 |
| Brexpiprazole | -2.5 |
| Quetiapine Extended Release | -2.8 |
Change From Baseline to Week 6 in PANSS Negative Subscale Score
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Negative Subscale score is calculated from 7 items (for example: blunted affect, emotional withdrawal and poor rapport). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -3.1 |
| Brexpiprazole | -3.7 |
| Quetiapine Extended Release | -4.5 |
Change From Baseline to Week 6 in PANSS Total Score
The Positive and Negative Syndrome Scale (PANSS) is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score (30 items) ranged from 30 to 210 with a higher score indicating greater severity of symptoms. (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -15.9 |
| Brexpiprazole | -20.0 |
| Quetiapine Extended Release | -24.0 |
Change From Baseline to Week 6 in PSP Total Score
The Personal and Social Performance Scale (PSP) is a clinician-rated scale designed and validated to measure a patient's current level of social functioning. The PSP scale consists of a 100-point single-item rating scale, subdivided into 10 equal intervals. Scores of 1 to 10 indicate lack of autonomy in basic functioning, whereas scores of 91 to 100 reflect excellent functioning. The total score is rated by the investigator and is based on an algorithm which takes both the ratings of the 4 primary domains of PSP, and the combination of these ratings into account. The 4 primary domains are: socially useful activities (including work and study), personal and social relationships, self-care, and disturbing and aggressive behaviours. The 4 domains are assessed on a 6-point scale, from absent to very severe. A higher score indicates a better performance. (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | 9.4 |
| Brexpiprazole | 13.0 |
| Quetiapine Extended Release | 15.3 |
Discontinuation Due to Lack of Efficacy During the Study
Discontinuation due to lack of efficacy was based on the primary reason for withdrawal (NCT01810380)
Timeframe: Baseline to Week 6
| Intervention | percentage of patients (Number) |
|---|
| Placebo | 14.91 |
| Brexpiprazole | 6.67 |
| Quetiapine Extended Release | 7.19 |
PSP Domain D: Disturbing and Aggressive Behaviours at Week 6
"PSP domain D: disturbing and aggressive behaviours were categorised as aggressive (corresponding to mild, manifest, marked, severe, or very severe) or nonaggressive (corresponding to absent)" (NCT01810380)
Timeframe: Week 6
| Intervention | percentage of aggressive patients (Number) |
|---|
| Placebo | 30.4 |
| Brexpiprazole | 27.2 |
| Quetiapine Extended Release | 22.2 |
PSP Functional Remission Rate at Week 6
The PSP functional remission rate was defined as a PSP total score ≥71 (NCT01810380)
Timeframe: Week 6
| Intervention | percentage of remitters (Number) |
|---|
| Placebo | 5.7 |
| Brexpiprazole | 9.6 |
| Quetiapine Extended Release | 14.4 |
PSP Functional Response Rate at Week 6
The PSP functional response rate was defined as ≥10 point improvement from Baseline on the PSP total score (NCT01810380)
Timeframe: Week 6
| Intervention | percentage of responders (Number) |
|---|
| Placebo | 36.3 |
| Brexpiprazole | 53.4 |
| Quetiapine Extended Release | 64.4 |
Response Rate at Week 6
The response rate was defined as a reduction of ≥30% from baseline in PANSS total score OR a CGI-I score of 1 or 2 (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | percentage of responders (Number) |
|---|
| Placebo | 32.1 |
| Brexpiprazole | 48.7 |
| Quetiapine Extended Release | 62.7 |
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: positive symptoms is calculated from 8 items (for example: delusions, conceptual disorganization and stereotype thinking). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -5.7 |
| Brexpiprazole | -7.1 |
| Quetiapine Extended Release | -8.4 |
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thoughts
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: disorganized thoughts is calculated from 7 items (for example: conceptual disorganization, difficulty in abstract thinking and mannerisms and posturing). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -3.2 |
| Brexpiprazole | -4.0 |
| Quetiapine Extended Release | -4.8 |
CGI-I Score at Week 6
"The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening).~The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not." (NCT01810380)
Timeframe: Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | 3.0 |
| Brexpiprazole | 2.7 |
| Quetiapine Extended Release | 2.5 |
Change From Baseline to Week 6 in CGI-S Score
"The Clinical Global Impression - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness.~The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients)." (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -0.9 |
| Brexpiprazole | -1.2 |
| Quetiapine Extended Release | -1.4 |
Change From Baseline to Week 6 in PANSS Excited Component Score
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Excited Component score is calculated from 5 items (for example: poor impulse control, tension and hostility). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -2.5 |
| Brexpiprazole | -3.3 |
| Quetiapine Extended Release | -3.9 |
Change From Baseline to Week 6 in PANSS General Psychopathology Subscale Score
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS General Psychopathology Subscale score is calculated from 16 items (for example: somatic concern, anxiety and guilt feelings). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -8.2 |
| Brexpiprazole | -9.9 |
| Quetiapine Extended Release | -11.6 |
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety/Depression
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: anxiety/depression is calculated from 4 items (for example: anxiety, guilt feelings, and tension). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms (NCT01810380)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -2.9 |
| Brexpiprazole | -3.2 |
| Quetiapine Extended Release | -3.6 |
Safety and Tolerability
Number of treatment-emergent adverse events (TEAEs) (NCT01810783)
Timeframe: Up to 52 weeks and a safety follow-up by telephone contact or clinic visit after 30 days after the last dose of investigational medicinal product (IMP)
| Intervention | TEAEs (Number) |
|---|
| Brexpiprazole | 337 |
Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
The Columbia Suicide Severity Rating Scale (eC-SSRS) is a semi-structured interview developed to systematically assess suicidal ideation and behaviour of patients participating in a clinical study. The C-SSRS has 5 questions addressing suicidal ideation, 5 sub-questions assessing the intensity of ideation, and 4 questions addressing suicidal behaviour. (NCT01837797)
Timeframe: From randomisation to end of treatment (week 20)
| Intervention | participants (Number) |
|---|
| No suicidal ideation or behaviour | Any non-suicidal self-injurious behavior | Suicidal Ideation | Preparatory action towards imminent suicidal behav | Not fatal suicide attempt | Completed suicide |
|---|
| Period 2 Brexpiprazole 1 mg and ADT | 3 | 0 | 0 | 0 | 0 | 0 |
,| Period 2 Brexpiprazole 3 mg and ADT | 4 | 0 | 2 | 0 | 0 | 0 |
,| Period 2 Placebo and ADT | 6 | 0 | 0 | 0 | 0 | 0 |
Number of Adverse Events
15 patients were enrolled to Period 2; only 3 patients completed due to study termination (NCT01837797)
Timeframe: From randomisation to follow-up (week 24)
| Intervention | Adverse events (Number) |
|---|
| Period 2 Placebo and ADT | 3 |
| Period 2 Brexpiprazole 1 mg and ADT | 5 |
| Period 2 Brexpiprazole 3 mg and ADT | 2 |
Full Remission During the Randomised Treatment Period
Full remission is defined as a Montomery and Åsberg Depression Rating Scale (MADRS) total score ≤10 and a ≥50% decrease from randomisation in MADRS total score for at least 8 consecutive weeks during randomized treatment. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). The MADRS total score is the sum of the 10 items. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | participants (Number) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 110 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 95 |
Response at Week 6 During the Randomised Treatment Period
Response is defined as a >=50% decrease from randomisation in MADRS total score. (NCT01838681)
Timeframe: From randomisation to week 6
| Intervention | participants (Number) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 76 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 82 |
Total Time in Remission During the Randomised Treatment Period
The total time the patient spends in remission during randomised treatment. Remission is defined as a MADRS total score <=10 and a >=50% decrease from randomisation in MADRS total score. Time in remission is defined as the sum of days over all periods between Period B visits where remission was obtained. The period between two visits is counted as in remission if the patient was in remission when the period started. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | Number of days (Mean) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 33.5 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 30.0 |
Time to Full Remission During the Randomised Treatment Period
The time from randomisation until full remission has been obtained. Full remission is defined as a MADRS total score ≤10 and a ≥50% decrease from randomisation in MADRS total score for at least 8 consecutive weeks during randomised treatment. The time to full remission was calculated using Kaplan-Meier Methods. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | Days (Median) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | NA |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | NA |
Full Remission Sustained During the Randomised Treatment Period
Full remission sustained is defined as having obtained full remission and remain in remission until completion of the study. Full remission is defined as a MADRS total score ≤10 and a ≥50% decrease from randomisation in MADRS total score for at least 8 consecutive weeks during randomised treatment. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | participants (Number) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 105 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 84 |
Remission at Week 24 in the Randomised Treatment Period
Remission is defined as a MADRS total score <=10 and a >=50% decrease from randomisation in MADRS total score. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | participants (Number) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 198 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 176 |
Remission at Week 6 During the Randomised Treatment Period
Remission is defined as a MADRS total score <=10 and a >=50% decrease from randomisation in MADRS total score. (NCT01838681)
Timeframe: From randomisation to week 6
| Intervention | participants (Number) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 46 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 53 |
Response at Week 24 During the Randomised Treatment Period
Response is defined as a >=50% decrease from randomisation in MADRS total score. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | participants (Number) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 236 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 223 |
Change From Randomisation to Week 24 in SDS Total Score During the Randomised Treatment Period
The SDS assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | -6.7 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | -5.5 |
Change From Randomisation to Week 6 in CGI-S Score During the Randomised Treatment Period
The CGI-S is a 7-point scale where the clinician rates the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. (NCT01838681)
Timeframe: From randomisation to week 6
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | -0.8 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | -0.8 |
Change From Randomisation to Week 6 in MADRS Total Score During the Randomised Treatment Period
The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). The MADRS total score is the sum of the 10 items. (NCT01838681)
Timeframe: From randomisation to week 6
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | -5.9 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | -6.3 |
Change From Randomisation to Week 6 in Q-LES-Q (SF) Total Score During the Randomised Treatment Period
The original Q-LES-Q is a patient self-rated scale designed to measure the degree of enjoyment and satisfaction experienced by patients in various areas of daily life. It consists of 93 items to measure: physical health, feelings, work, household duties, school, leisure time activities, social relations, and general activities. The Q-LES-Q short form (SF) contains 16 items from the general activities section. Each item is rated on a 5-point scale ranging from 1 (very poor) to 5 (very good). The total score is the sum of the first 14 items. The last two scores are stand-alone items. The total score ranges from 14 to 70. (NCT01838681)
Timeframe: From randomisation to week 6
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 3.5 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 3.2 |
Change From Randomisation to Week 6 in SDS Total Score During the Randomised Treatment Period
The SDS assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. (NCT01838681)
Timeframe: From randomisation to week 6
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | -3.0 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | -2.9 |
Full Functional Remission During the Randomised Treatment Period
Full functional remission is defined as a Sheehan Disability Scale (SDS) total score <=6 and all SDS domain scores <=2 observed for at least 8 consecutive weeks during the randomised treatment period. The SDS assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | participants (Number) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 73 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 68 |
Full Global Score Remission During the Randomised Treatment Period
Full global score remission is defined as a Clinical Global Impression - Severity of Illness (CGI-S) score <=2 observed for at least 8 consecutive weeks during the randomised treatment period. The CGI-S is a 7-point scale where the clinician rates the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis, on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | participants (Number) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 143 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 121 |
Change From Randomisation to Week 24 in CGI-S Score During the Randomised Treatment Period
The CGI-S is a 7-point scale where the clinician rates the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | -1.7 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | -1.5 |
Change From Randomisation to Week 24 in MADRS Total Score During the Randomised Treatment Period
The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). The MADRS total score is the sum of the 10 items. (NCT01838681)
Timeframe: From randomisation to end of Period B (24 weeks)
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | -12.6 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | -11.5 |
Mean Change From Baseline in Clinical Global Impression-Improvement (CGI-I) Score
The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at baseline. Response choices include: 0 = not assessed; 1 =very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 =minimally worse; 6 = much worse; and 7 = very much worse. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation. (NCT01854944)
Timeframe: Baseline to Day 6, 11 and Last Visit
| Intervention | Units on a scale (Mean) |
|---|
| Day 6 | Day 11 |
|---|
| Cohort 1 - Brexpiprazole 4mg | 4.0 | 3.5 |
,| Cohort 2- Brexpiprazole 1mg | 4.0 | 3.8 |
,| Cohort 3 Brexpiprazole 4mg | 4.0 | 2.7 |
Change in Percentage 5-HT2A Receptor Occupancy
Mean (±SD) Serotonin 5-HT2A Receptor Occupancy Using the Radiotracer [11C]MDL100907 (in low and high dose). The 5-HT2A receptors following administration of 1- and 4-mg doses of brexpiprazole were assessed and the occupancy estimates were averaged across brain regions 4 hours post-last dose on Day 10. (NCT01854944)
Timeframe: Baseline and 4 hours post-last dose on Day 10
| Intervention | percentage occupancy (Mean) |
|---|
| Brexpiprazole 1mg | 28 |
| Brexpiprazole 4 mg | 45 |
Change in Percentage 5-HT1A Receptor Occupancy
Mean (±SD) Serotonin 5-HT1A Receptor Occupancy Using the Radiotracer [11C]CUMI101 in high dose only. In cohorts 1, 2 and 3, the binding of brexpiprazole to the 5-HT1A receptors was assessed by comparing the binding potential from the Baseline scan (prior to treatment) to that of Day 10 (after treatment). The 5-HT1A receptors following administration of a 4-mg dose of brexpiprazole was assessed and the occupancy estimates were averaged across brain regions 4 hours post-last dose on Day 10. (NCT01854944)
Timeframe: Baseline to 4 hours post-last dose on Day 10
| Intervention | percentage occupancy (Mean) |
|---|
| Brexpiprazole 4mg | 4 |
Change in Occupancy at Serotonin Transporter (SERT)
Mean (±SD) SERT Occupancy Using the Radiotracer [11C]DASB in high dose only. Occupancy estimates were averaged across brain regions 4 hours post-last dose. (NCT01854944)
Timeframe: Baseline to 4 hours post-last dose on Day 10
| Intervention | percentage occupancy (Mean) |
|---|
| Brexpiprazole 4mg | -3 |
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score
The BARS consisted of 4 items related to akathisia: objective observation of akathisia by the study physician, subjective feelings of restlessness by the participant, participant distress due to akathisia, and global evaluation of akathisia. The first 3 items were rated on a 4-point scale, with a score of 0 = absence of symptoms and a score of 3 = severe condition. The global clinical evaluation were made on a 6-point scale, (0=absent, 1=questionable, 2=mild, 3=moderate, 4=marked, 5=severe). To complete this scale, participants were observed while they were seated and then stood for a minimum of 2 minutes in each position. Symptoms observed in other situations (e.g., while engaged in neutral conversation or engaged in activity on the ward) may also be rated. Subjective phenomena were to be elicited by direct questioning. The BARS total score (when combined) ranged from 0 to 18, with higher values indicating a severe condition. (NCT01854944)
Timeframe: Baseline to Day 6, 11 and Last Visit
| Intervention | Units on a scale (Mean) |
|---|
| Day 6 | Day 11 | Last Visit |
|---|
| Cohort 1 - Brexpiprazole 4mg | 0.5 | 0.5 | 0.5 |
,| Cohort 2- Brexpiprazole 1mg | 0 | 0 | 0 |
,| Cohort 3 Brexpiprazole 4mg | 0.5 | 0.0 | 0.0 |
Apparent Clearance of Drug From Plasma After Extravascular Administration (CL/F; Only Brexpiprazole)
PK parameter - CL/F was assessed for brexpiprazole only. Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose. (NCT01854944)
Timeframe: Baseline to Day 10
| Intervention | mL/hr (Mean) |
|---|
| Cohort 1 - Brexpiprazole 4 mg | 1960 |
| Cohort 2 - Brexpiprazole 1mg | 1420 |
| Cohort 3 - Brexpiprazole 4mg | 2970 |
Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score
The AIMS Scale was an extrapyramidal symptoms (EPS) rating scale. The AIMS is a 12 item scale. The first 10 items e.g. facial and oral movements (items 1-4), extremity movements (items 5 and 6), trunk movements (item 7), investigators global assessment of dyskinesia (items 8 to 10). The first 10 items are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28, with a higher score indicating worse outcome. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation. (NCT01854944)
Timeframe: Baseline to Day 6, 11 and Last Visit
| Intervention | Units on a scale (Mean) |
|---|
| Day 6 | Day 11 | Last Visit |
|---|
| Cohort 1 - Brexpiprazole 4mg | 0 | 0 | 0 |
,| Cohort 2 - Brexpiprazole 1mg | 0 | 0 | 0 |
,| Cohort 3 Brexpiprazole 4mg | 0.3 | 0 | 0 |
Change in Percentage Dopamine D2/D3 Receptor Occupancy
Dopamine receptor occupancy measured using the radiotracer [11C]-(+)-PHNO in low and high dose. The binding of brexpiprazole to the D2/D3 receptors were assessed by comparing the binding potential from the Baseline scan (prior to treatment) to that of Day 10 (after treatment). The D2/D3 receptors following administration of a 1- and 4-mg doses of brexpiprazole were assessed and the occupancy estimates were averaged across brain regions 4 hours post-last dose on Day 10. (NCT01854944)
Timeframe: Baseline to 4 hours post-last dose on Day 10
| Intervention | percentage occupancy (Mean) |
|---|
| 6-region model (D2 receptor) | 6-region model (D3 receptor) | 8-region model (D2 receptor) | 8-region model (D3 receptor) |
|---|
| Brexpiprazole 1mg | 36 | 2 | 27 | 1 |
,| Brexpiprazole 4 mg | 59 | 13 | 67 | 31 |
Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score
"The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation." (NCT01854944)
Timeframe: Baseline to Day 6, 11 and Last Visit
| Intervention | Units on a scale (Mean) |
|---|
| Day 6 | Day 11 | Last Visit |
|---|
| Cohort 1 - Brexpiprazole 4mg | 0.3 | 0.5 | 0.5 |
,| Cohort 2- Brexpiprazole 1mg | 0.0 | 0.0 | 0.0 |
,| Cohort 3 Brexpiprazole 4mg | 0.8 | 1.0 | 0.8 |
Percentage of Participants Who Reported at Least One Occurrence of Suicidality, Suicidal Behavior and Suicidal Ideation on the Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Suicidality was defined as reporting at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any type of suicidal behaviors (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). The suicidal ideation intensity total score is the sum of intensity scores of 5 items (frequency, duration, controllability, deterrents, and reasons for ideation). The score of each intensity item ranges from 0 (none) to 5 (worst) which leads to the range of the total score from 0 to 25, with a higher score indicating a worse outcome. A missing score of any item resulted in a missing total score. If no suicidal ideation was reported, a score of 0 was given to the intensity scale. Last Visit is last scheduled post-baseline evaluation including early termination evaluation. (NCT01854944)
Timeframe: Baseline to Last Visit
| Intervention | Percentage of participants (Number) |
|---|
| Suicidality | Suicidal behaviour | Suicidal Ideation |
|---|
| Cohort 1 - Brexpiprazole 4mg | 0 | 0 | 0 |
,| Cohort 2- Brexpiprazole 1mg | 0 | 0 | 0 |
,| Cohort 3 Brexpiprazole 4mg | 0 | 0 | 0 |
Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score
The SAS is a rating scale used to measure EPS. The SAS scale consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40, with higher scores indicating worse outcome. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation. (NCT01854944)
Timeframe: Baseline to Day 6, 11 and Last Visit
| Intervention | Units on scale (Mean) |
|---|
| Day 6 | Day 11 | Last Visit |
|---|
| Cohort 1 - Brexpiprazole 4mg | 0.3 | 0 | 0 |
,| Cohort 2- Brexpiprazole 1mg | 0 | 0 | 0 |
,| Cohort 3 Brexpiprazole 4mg | -0.3 | -0.7 | -0.5 |
Mean Change From Baseline in Positive and Negative Symptom Scale (PANSS) Total Score
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation. (NCT01854944)
Timeframe: Baseline to Day 6, 11 and Last Visit
| Intervention | Units on a scale (Mean) |
|---|
| Day 6 | Day 11 | Last Visit |
|---|
| Cohort 1 - Brexpiprazole 4mg | -4.0 | -1.5 | -1.5 |
,| Cohort 2 - Brexpiprazole 1mg | 0.3 | 6.0 | 6.0 |
,| Cohort 3 - Brexpiprazole 4mg | -2.0 | -4.0 | -3.0 |
Mean Change From Baseline in PANSS Negative Subscale Score
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation. (NCT01854944)
Timeframe: Baseline to Day 6, 11 and Last Visit
| Intervention | Units on a scale (Mean) |
|---|
| Day 6 | Day 11 | Last Visit |
|---|
| Cohort 1 - Brexpiprazole 4mg | -2.5 | -1.5 | -1.5 |
,| Cohort 2- Brexpiprazole 1mg | 1.0 | 0.5 | 0.5 |
,| Cohort 3 Brexpiprazole 4mg | 0.3 | -0.3 | -0.3 |
Mean Change From Baseline in PANNS Positive Subscale Score
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation. (NCT01854944)
Timeframe: Baseline to Day 6, 11 and Last Visit
| Intervention | Units on a scale (Mean) |
|---|
| Day 6 | Day 11 | Last Visit |
|---|
| Cohort 1 - Brexpiprazole 4mg | -0.8 | 0.5 | 0.5 |
,| Cohort 2- Brexpiprazole 1mg | 0.0 | 0.5 | 0.5 |
,| Cohort 3 Brexpiprazole 4mg | -0.8 | -2.7 | -2.0 |
Change From Baseline In The Cohen-Mansfield Agitation Inventory (CMAI) Total Score After 12 Weeks Of Brexpiprazole Treatment
"To compare the efficacy of 2 fixed doses (1 mg/day and 2 mg/day) of brexpiprazole with placebo in participants with agitation associated with dementia of the Alzheimer's type, by the assessment of CMAI after 12 weeks of treatment. The CMAI assesses the frequency of agitated behaviors in elderly persons, such as hitting, cursing, and restlessness. It consists of 29 items all rated on a 1 to 7 scale with 1 being the best rating and 7 being the worst rating. The minimum possible CMAI total score is 29, and the maximum possible CMAI total score is 203. A decrease in score indicates improvement in symptoms. To control the overall type I error at 0.05 level when making 2 comparisons of brexpiprazole doses versus placebo, statistical testing was carried out using a hierarchical testing procedure in the order of: 1) comparison of 2 mg/day brexpiprazole versus placebo, and 2) comparison of 1 mg/day brexpiprazole versus placebo." (NCT01862640)
Timeframe: Baseline, Week 12/Early Termination (ET)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg/Day | -21.6 |
| Brexpiprazole 1 mg/Day | -17.6 |
| Placebo | -17.8 |
Change From Baseline to Week 12/Early Termination in the Cohen-Mansfield Agitation Inventory (CMAI) Total Score
"The CMAI is widely used in clinical research for evaluation of agitation associated with Alzheimer's dementia, with reliability and validity in both institutionalized and noninstitutionalized participants. It consists of 29 items, all rated on a 1 to 7 scale (1=Never and 7=Several times in an hour), with 1 being the best rating and 7 being the worst rating. The total score is the sum of ratings for all 29 items. The possible total scores range from 29 to 203. The total score will be unevaluable if less than 24 of the 29 items are recorded. If 24 to 28 of the 29 items are recorded, the total score will be the mean of the recorded items multiplied by 29 and rounded to the first decimal place. The mean change from baseline (Day 0) to week 12 in the CMAI total score is reported. Statistical comparison of interest was brexpiprazole flexible dose versus placebo, analyzed using a mixed-effect model repeated measure approach. A decrease in score indicates improvement in symptoms." (NCT01922258)
Timeframe: From screening to week 12/early termination
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole (Flexible Dose Range 0.5 to 2 mg/Day) | -18.9 |
| Placebo (Flexible Dose Range 0.5 to 2 mg/Day) | -16.5 |
Percentage of MADRS Responders at Week 8
The Montgomery Aasberg Depression Rating Scale (MADRS) is a 10-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Items in the scale assess apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Symptoms are rated on a 7-point scale from 0 (no symptoms) to 6 (severe symptoms). Definitions of severity are provided at two-point intervals. The total score of the 10 items ranges from 0 to 60, with higher values indicating worse outcome. Response was defined as a ≥50% decrease in MADRS total score from baseline. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Week 8
| Intervention | percentage of patients (Number) |
|---|
| Brexpiprazole | 56 |
Changes From Baseline to Week 8 on Number of Awakenings (NAW) as Assessed by Actigraphy (ACT)
The key ACT parameters assessed were the total sleep time (ACT TST), sleep efficiency (ACT SE), sleep onset latency (ACT SOL), wake-time after sleep onset (ACT WASO), and the number of awakenings (ACT NAW). The results for ACT TST, ACT SE, ACT WASO, and ACT NAW are presented separately from ACT SOL as the number of patients available for analysis was different. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | number of events (Mean) |
|---|
| Brexpiprazole | -2.0 |
Change From Baseline to Week 8 in ISI Total Score
The Insomnia Severity Index (ISI) is a patient-rated scale desgined to measure the patient's perception of his/her insomnia. The ISI comprises 7 items: difficulty falling asleep, difficulty staying asleep, problems waking up early in the morning, satisfaction with current sleep pattern, interference with daily functioning, how much others notice the sleep problem impairs quality of life, and distress caused by the sleep problem. Each of the 7 items is rated on a 5-point scale from 0 (best situation) to 4 (worst situation). The total score of the 7 items ranges from 0 to 28, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -9.2 |
Changes From Baseline to Week 8 in Circadian and Biological Rhythm
The parameters used to assess circadian and biological rhythm were the time to peak cortisol concentration, time to dim-light melatonin onset (DLMO) and phase angle. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | minutes (Mean) |
|---|
| Time to peak cortisol concentration | Time to DLMO | Phase angle |
|---|
| Brexpiprazole | -60 | 48 | 108 |
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography
The key sleep architecture parameters assessed with polysomnography were the percentage of time and duration spent in Stages N1 (non-rapid eye movement [non-REM]), N2 (non-REM), N3 (non-REM), and REM, respectively, as well as the duration of latency to REM sleep. The results for the percentage of time spent at each stage is presented separately from the duration due to the different units of measurement involved. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | percentage of total sleep duration (Mean) |
|---|
| Stage N1 (n=40) | Stage N2 (n=40) | Stage N3 (n=40) | Stage REM (n=40) |
|---|
| Brexpiprazole | -0.7 | 3.5 | -2.2 | -0.6 |
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography (Continued)
The key sleep architecture parameters assessed with polysomnography were the percentage of time and duration spent in Stages N1 (non-rapid eye movement [non-REM]), N2 (non-REM), N3 (non-REM), and REM, respectively, as well as the duration of latency to REM sleep. The results for the percentage of time spent at each stage is presented separately from the duration due to the different units of measurement involved. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | minutes (Mean) |
|---|
| Stage N1 Duration (n=41) | Stage N2 Duration (n=41) | Stage N3 Duration (n=41) | Stage REM Duration (n=41) | Latency to REM Sleep Duration (n=38) |
|---|
| Brexpiprazole | 4.5 | 43.1 | -3.1 | 4.5 | -16.2 |
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Actigraphy (ACT) Parameters
The key ACT parameters assessed were the total sleep time (ACT TST), wake-time after sleep onset (ACT WASO), sleep onset latency (ACT SOL), sleep efficiency (ACT SE), and the number of awakenings (ACT NAW). The results for ACT TST, ACT WASO, and ACT SOL are presented separately from ACT SE, and from ACT NAW, due to the different units of measurement involved. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | minutes (Mean) |
|---|
| ACT TST (n=33) | ACT WASO (n=33) | ACT SOL (n=32) |
|---|
| Brexpiprazole | -9.0 | -6.1 | -5.5 |
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Parameters
The key PSG parameters assessed were the latency to persistent sleep (PSG LPS), sleep onset latency (PSG SOL), wake-time after sleep onset (PSG WASO), total sleep time (PSG TST), number of awakenings (PSG NAW), and sleep efficiency (PSG SE). The results for PSG LPS, PSG SOL, PSG WASO, and PSG TST are presented separately from the PSG NAW, and from the PSG SE due to the different units of measurement involved. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | minutes (min) (Mean) |
|---|
| PSG LPS (n=40) | PSG SOL (n=40) | PSG WASO (n=40) | PSG TST (n=41) |
|---|
| Brexpiprazole | -24.9 | -19.7 | -26.4 | 49.0 |
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M)
The key CSD-M parameters assessed were the sleep efficiency (CSD-M SE), total sleep time (CSD-M TST), sleep onset latency (CSD-M SOL), wake-time after sleep onset (CSD-M WASO), and number of awakenings (CSD-M NAW). The results for CSD-M SE are presented separately from CSD-M TST, CSD-M SOL, and CSD-M WASO, and from CSD-M NAW due to the different units of measurement involved. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | minutes (min) (Mean) |
|---|
| CSD-M TST (n=21) | CSD-M SOL (n=21) | CSD-M WASO (n=21) |
|---|
| Brexpiprazole | 69.9 | -37.1 | -42.9 |
Change From Baseline to Week 8 on BL-VAS-s (Morning) Score
The Bond-Lader Visual Analogue Scale - Sedation (BL-VAS-s) is a patient-rated scale designed to assess the current level of sedation. The BL-VAS-s was assessed for the evening (19:00 to 23:59 hours), morning (00:00 to 08:59 hours) and at noon (11:00 to 13:59 hours). The BL-VAS-s is a single item scale rated on a 100mm visual analogue scale. The score is measured from the left to a mark made on the line by the patient and ranges from 0 (alert) to 100 (drowsy). As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -9.2 |
Change From Baseline to Week 8 on BL-VAS-s Scores (Noon)
The Bond-Lader Visual Analogue Scale - Sedation (BL-VAS-s) is a patient-rated scale designed to assess the current level of sedation. The BL-VAS-s was assessed for the evening (19:00 to 23:59 hours), morning (00:00 to 08:59 hours) and at noon (11:00 to 13:59 hours). The BL-VAS-s is a single item scale rated on a 100mm visual analogue scale. The score is measured from the left to a mark made on the line by the patient and ranges from 0 (alert) to 100 (drowsy). As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -7.4 |
Change From Baseline to Week 8 on ESS Total Score
The Epworth Sleepiness Scale (ESS) is a is a patient-rated scale designed to measure daytime sleepiness. The ESS consists of 8 items describing different situations/activities and the patients rate the chance of them dozing off or falling asleep when they are in these situations. Each item is rated on a 4-point scale from 0 (would never dose) to 3 (high change of dozing). The total score of the 8 items ranges from 0 to 24, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -2.6 |
Changes From Baseline to Week 8 in Number of Lapses as Assessed Using a PVT Device
The psychomotor vigilance task (PVT) measures sustained or vigilant attention by recording response time (milliseconds) to a visual/or auditory stimulus that appears at random inter-stimulus intervals (range: from 2 to 10 seconds). The patient was instructed to monitor a red rectangular box on the computer screen and to press a response button as soon as a yellow stimulus counter appeared on the screen. The parameters assessed using a PVT device were response speed and number of lapses. The results for response speed is presented separately from the number of lapses due to the different units of measurement involved. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | number (Mean) |
|---|
| Brexpiprazole | 2.1 |
Change From Baseline to Week 8 in CPFQ Total Score
The Cognitive and Physical Functioning Questionnaire (CPFQ) is a patient-rated scale designed to assess cognitive and executive dysfunction including symptoms of fatigue in mood and anxiety disorders. The CPFQ consists of 7 items, each rated on a scale from 1 (greater than normal functioning) to 6 (poorer than normal functioning). The total score of the 7 items ranges from 7 to 42, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -8.4 |
Change From Baseline to Week 8 in CGI-S Score
The Clinical Global Impression - Severity of Illness (CGI-S) scale assesses the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients), with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -1.8 |
Changes From Baseline to Week 8 on Sleep Efficiency (SE) as Assessed by Actigraphy (ACT)
The key ACT parameters assessed were the total sleep time (ACT TST), sleep efficiency (ACT SE), sleep onset latency (ACT SOL), wake-time after sleep onset (ACT WASO), and the number of awakenings (ACT NAW). The results for ACT TST, ACT SE, ACT WASO, and ACT NAW are presented separately from ACT SOL as the number of patients available for analysis was different. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | percentage of time (Mean) |
|---|
| Brexpiprazole | -1.3 |
CGI-I Score at Week 8
The Clinical Global Impression - Global Improvement (CGI-I) assesses the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | 2.2 |
Change From Baseline to Week 8 in MADRS Total Score
The Montgomery Aasberg Depression Rating Scale (MADRS) is a 10-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Items in the scale assess apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Symptoms are rated on a 7-point scale from 0 (no symptoms) to 6 (severe symptoms). Definitions of severity are provided at two-point intervals. The total score of the 10 items ranges from 0 to 60, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -16.0 |
Changes From Baseline to Week 8 in Response Speed as Assessed Using a PVT Device
The psychomotor vigilance task (PVT) measures sustained or vigilant attention by recording response time (milliseconds) to a visual/or auditory stimulus that appears at random inter-stimulus intervals (range: from 2 to 10 seconds). The patient was instructed to monitor a red rectangular box on the computer screen and to press a response button as soon as a yellow stimulus counter appeared on the screen. The parameters assessed using a PVT device were response speed and number of lapses. The results for response speed is presented separately from the number of lapses due to the different units of measurement involved. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | speed (per second) (Mean) |
|---|
| Brexpiprazole | -0.2 |
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Number of Awakenings (PSG NAW)
The key PSG parameters assessed were the latency to persistent sleep (PSG LPS), sleep onset latency (PSG SOL), wake-time after sleep onset (PSG WASO), total sleep time (PSG TST), number of awakenings (PSG NAW), and sleep efficiency (PSG SE). The results for PSG LPS, PSG SOL, PSG WASO, and PSG TST are presented separately from the PSG NAW, and from the PSG SE due to the different units of measurement involved. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | number of events (Mean) |
|---|
| Brexpiprazole | 0.06 |
Change From Baseline to Week 8 in BRIAN Total Score
The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) is a clinician-rated scale designed to assess biological rhythms. The BRIAN consists of 18 items divided in 4 subscales: sleep (5 items), activity (5 items), social (4 items), and eating pattern (4 items). Each item is rated on a scale from 1 (no difficulties) to 4 (serious difficulties). The total score of the 18 items ranges from 18 to 72, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -17.4 |
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Sleep Efficiency (PSG SE)
The key PSG parameters assessed were the latency to persistent sleep (PSG LPS), sleep onset latency (PSG SOL), wake-time after sleep onset (PSG WASO), total sleep time (PSG TST), number of awakenings (PSG NAW), and sleep efficiency (PSG SE). The results for PSG LPS, PSG SOL, PSG WASO, and PSG TST are presented separately from the PSG NAW, and from the PSG SE due to the different units of measurement involved. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | percentage (%) (Mean) |
|---|
| Brexpiprazole | 10.4 |
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Number of Awakenings (NAW)
The key CSD-M parameters assessed were the sleep efficiency (CSD-M SE), total sleep time (CSD-M TST), sleep onset latency (CSD-M SOL), wake-time after sleep onset (CSD-M WASO), and number of awakenings (CSD-M NAW). As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | number (Mean) |
|---|
| Brexpiprazole | 0.0 |
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Sleep Efficiency (SE)
The key CSD-M parameters assessed were the sleep efficiency (CSD-M SE), total sleep time (CSD-M TST), sleep onset latency (CSD-M SOL), wake-time after sleep onset (CSD-M WASO), and number of awakenings (CSD-M NAW). The results for CSD-M SE are presented separately from CSD-M TST, CSD-M SOL, and CSD-M WASO, and from CSD-M NAW due to the different units of measurement involved. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | percentage of time (Mean) |
|---|
| Brexpiprazole | 13.4 |
Percentage of MADRS Remitters at Week 8
The Montgomery Aasberg Depression Rating Scale (MADRS) is a 10-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Items in the scale assess apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Symptoms are rated on a 7-point scale from 0 (no symptoms) to 6 (severe symptoms). Definitions of severity are provided at two-point intervals. The total score of the 10 items ranges from 0 to 60, with higher values indicating worse outcome. Remission was defined as a MADRS total score ≤10 and a ≥50% decrease in MADRS total score from baseline. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Week 8
| Intervention | percentage of patients (Number) |
|---|
| Brexpiprazole | 54 |
Change From Baseline to Week 8 on BL-VAS-s (Evening) Score
The Bond-Lader Visual Analogue Scale - Sedation (BL-VAS-s) is a patient-rated scale designed to assess the current level of sedation. The BL-VAS-s was assessed for the evening (19:00 to 23:59 hours), morning (00:00 to 08:59 hours) and at noon (11:00 to 13:59 hours). The BL-VAS-s is a single item scale rated on a 100mm visual analogue scale. The score is measured from the left to a mark made on the line by the patient and ranges from 0 (alert) to 100 (drowsy). As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942733)
Timeframe: Baseline and Week 8
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | 1.4 |
Change From Week 6 to Week 10 in BIS-11 Total Score
The Barratt Impulsiveness Scale, Version 11 (BIS-11) is a patient-rated scale designed to assess impulsive personality traits. The BIS-11 consists of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provide information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, non-planning impulsiveness, and attentional impulsiveness). The total score ranges from 30 to 120 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Week 6 and Week 10
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -1.2 |
Change From Week 6 to Week 10 in CGI-S Score
The Clinical Global Impression severity of illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Week 6 and Week 10
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | 0.3 |
Change From Week 6 to Week 10 in Delay Discounting - MCQ Scores
"The Monetary Choice Questionnaire (MCQ) is a patient-completed questionnaire designed to measure delay discounting, an index of impulsive behaviour. The MCQ consists of 27 choices between immediate and delayed rewards. The patients choose repeatedly between two hypothetical sums of money: a smaller amount now or a larger amount in the future (for example, ''Would you prefer $27 today or $50 in 21 days?). The answers provide an estimate of the patient's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicate impulsivity. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes." (NCT01942785)
Timeframe: Week 6 and Week 10
| Intervention | log-transformed units on a scale (Mean) |
|---|
| Brexpiprazole | 0.35 |
Change From Week 6 to Week 10 in KSQ Anger-hostility Subscore
The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ anger-hostility subscale score ranges from 0 to 23 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Week 6 and Week 10
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | 1.2 |
Change From Week 6 to Week 10 in KSQ Depression Subscore
The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ depression subscale score ranges from 0 to 23, with higher values indicating worse outcome . As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Week 6 and Week 10
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | 2.1 |
Change From Week 6 to Week 10 in SIS Item 1 Score
The Sheehan Irritability Scale (SIS) is a patient-rated scale designed to measure irritability. The SIS item 1 assess how much the patient has suffered from irritability in the past week, using verbal descriptors (not at all, mildly, moderately, markedly, and extremely) as well as numerical scores from 0 (not at all) to 10 (extremely) that provide more precise levels of the verbal descriptors. The SIS item 1 ranged from 0 to 10 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Week 6 and Week 10
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | 0.5 |
Change From Week 6 to Week 10 in SIS Total Score
The Sheehan Irritability Scale (SIS) is a patient-rated scale designed to measure irritability. The SIS consists of 7 subscales assessing irritability, frustration, edginess/impatience/overreaction, moodiness, anger with self, anger with others, and temper. The patient rates the extent to which they have suffered from these symptoms. Each subscale has verbal descriptors (not at all, mildly, moderately, markedly, and extremely) as well as numerical scores from 0 (not at all) to 10 (extremely) that provide more precise levels of the verbal descriptors. One additional question assesses number of days impaired by irritability over the period. The subscales are summarised to give the total score which ranges from 0 to 70, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Week 6 and Week 10
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | 4.4 |
CGI-I Score at Week 6 Patients With a Pre-defined Baseline BIS-11 Total Score
The subgroups denoted BIS-11_HIGH had a BIS-11 total score at Baseline ≥median at baseline and the subgroups denoted BIS-11_LOW had a BIS-11 total score NCT01942785)
Timeframe: Week 6
| Intervention | units on a scale (Mean) |
|---|
| BIS-11_HIGH (n=27) | BIS-11_LOW (n=23) |
|---|
| Brexpiprazole | 2.48 | 1.83 |
Change From Baseline to Week 6 in CGI-S Score in Patients With a Pre-defined Baseline BIS-11 Total Score
The subgroups denoted BIS-11_HIGH had a BIS-11 total score at Baseline ≥median at baseline and the subgroups denoted BIS-11_LOW had a BIS-11 total score NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| BIS-11_HIGH (n=27) | BIS-11_LOW (n=27) |
|---|
| Brexpiprazole | -1.31 | -1.53 |
Change From Baseline to Week 6 in MADRS Total Score in Patients With a Pre-defined Baseline BIS-11 Total Score
The Montgomery and Åsberg Depression Rating Scale (MADRS) is a 10-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). The total score of the 10 items ranges from 0 to 60, with higher values indicating worse outcome. Subgroup analyses were performed for the change from Baseline to Week 6 in MADRS total score based on the patients' BIS-11 total score at Baseline. The subgroups denoted BIS-11_HIGH had a BIS-11 total score at Baseline ≥median at baseline and the subgroups denoted BIS-11_LOW had a BIS-11 total score NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| BIS-11_HIGH (n=27) | BIS-11_LOW (n=27) |
|---|
| Brexpiprazole | -14.41 | -15.45 |
Shift From Baseline to Week 6 in Anger Attacks (AAQ)
The Anger Attacks Questionnaire (AAQ) is a patient-rated scale designed to assess the presence of anger attacks over a period of time. The AAQ consists of 7 items. Patients are classified as having anger attacks when exhibiting the following 4 criteria: 1) irritability, 2) overreaction to minor annoyances, 3) occurrence of anger attacks (at least one of which occurred within the period), and 4) experienced 4 or more specific symptoms during at least one of the attacks. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | participants (Number) |
|---|
| no to no | no to yes | yes to no | yes to yes |
|---|
| Brexpiprazole | 28 | 5 | 15 | 2 |
Change From Baseline to Week 6 in IDS-C30 Total Score
The 30-item Inventory of Depressive Symptomatology - Clinician-Rated (IDS-C30) is a clinician-rated scale designed to assess the severity of depressive symptoms. The IDS-C30 consists of 30 items assessing the symptoms of depression, as well as commonly associated symptoms (for example, anxiety, irritability), and topics relevant to melancholic or atypical features; the patient rates only one of the 2 items assessing appetite (decreased or increased), and only one of the 2 items assessing weight (loss or gain). Each of the items is rated on a 4-point anchored scale from 0 (least severe) to 3 (most severe). The total score is the sum of the 28 scored items, and ranges from 0 to 84, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -17.81 |
CGI-I Score at Week 6
The Clinical Global Impression - global improvement CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | 2.18 |
Change From Baseline to Week 6 in BIS-11 Total Score
The Barratt Impulsiveness Scale, Version 11 (BIS-11) is a patient-rated scale designed to assess impulsive personality traits. The BIS-11 consists of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The total score ranges from 30 to 120 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -4.85 |
Change From Baseline to Week 6 in CGI-S Score
The Clinical Global Impression severity of illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -1.43 |
Change From Baseline to Week 6 in CPFQ Total Score
The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a patient-rated scale designed to assess cognitive and executive dysfunction including symptoms of fatigue in mood and anxiety disorders. The CPFQ consists of 7 items, each rated on a scale from 1 (greater than normal functioning) to 6 (poorer than normal functioning). The total score of the 7 items ranges from 7 to 42, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -7.72 |
Change From Baseline to Week 6 in Delay Discounting - EDT DRT Score
DRT consists of 60 choices between an immediate reward or a higher delayed reward. The number of impulsive choices will be a continuous variable estimated from how many immediate choices based on 60 possible. The number ranges between 0 and 60, with a higher value indicating more impulsivity. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | 0.74 |
Change From Baseline to Week 6 in IDS-C30 Item 6 Score
The 30-item Inventory of Depressive Symptomatology - Clinician-Rated (IDS-C30) is a clinician-rated scale designed to assess the severity of depressive symptoms. The IDS-C30 item 6 measures mood (irritable) and is rated on a 4-point anchored scale from 0 (least severe) to 3 (most severe) with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -1.22 |
Change From Baseline to Week 6 in KSQ Anger-hostility Subscore
The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ anger-hostility subscale score ranges from 0 to 23 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -7.72 |
Change From Baseline to Week 6 in KSQ Depression Subscore
The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ depression subscale score ranges from 0 to 23, with higher values indicating worse outcome . As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -7.70 |
Change From Baseline to Week 6 in KSQ Total Score
"The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ consists of 92 items which form the basis for the four subscales: depression, anxiety, anger-hostility, and somatic; of which 68 items indicate symptoms (symptom subscales) and 24 items are antonyms of some of the symptoms and indicate well-being (well-being subscales). A yes or true response on the symptom subscales scores 1, and a no or false on the well-being subscales scores 1. The maximum score for each symptom subscale is 17, and the maximum score for each well-being subscale is 6. The score of each subscale ranges from 0 to 23 (the sum of the symptom subscale and the well-being subscale). A higher score indicates more distress. The total score ranges from 0 to 92. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes." (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -24.36 |
Change From Baseline to Week 6 in MADRS Total Score
The Montgomery and Åsberg Depression Rating Scale (MADRS) is a 10-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). The total score of the 10 items ranges from 0 to 60, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -14.19 |
Change From Baseline to Week 6 in SIS Item 1 Score
The Sheehan Irritability Scale (SIS) is a patient-rated scale designed to measure irritability. The SIS item 1 assess how much the patient has suffered from irritability in the past week. The SIS item 1 ranged from 0 to 10 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -3.45 |
Change From Baseline to Week 6 in SIS Total Score
The Sheehan Irritability Scale (SIS) is a patient-rated scale designed to measure irritability. The SIS consists of 7 subscales assessing irritability, frustration, edginess/impatience/overreaction, moodiness, anger with self, anger with others, and temper. The subscales are summarised to give the total score which ranges from 0 to 70, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes. (NCT01942785)
Timeframe: Baseline and Week 6
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -21.13 |
Number of Participants With Treatment-Emergent Adverse Events
Number of participants with Treatment-Emergent Adverse Events (NCT01944969)
Timeframe: From baseline to Week 52
| Intervention | participants (Number) |
|---|
| Brexpiprazole and ADT | 28 |
Number of Withdrawals
Number of withdrawals (NCT01944969)
Timeframe: From baseline to Week 52
| Intervention | participants (Number) |
|---|
| Brexpiprazole and ADT | 26 |
Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
The Columbia Suicide Severity Rating Scale (eC-SSRS) is a semi-structured interview developed to systematically assess suicidal ideation and behaviour of patients participating in a clinical study. The C-SSRS has 5 questions addressing suicidal ideation, 5 sub-questions assessing the intensity of ideation, and 4 questions addressing suicidal behaviour. The electronic C-SSRS (eC-SSRS) is a patient-rated electronic version using interactive voice response technology. A structured CSSRS script of standardised questions, follow-up prompts, error-handling and scoring conventions is used for administration. (NCT01944969)
Timeframe: From baseline to Week 52
| Intervention | participants (Number) |
|---|
| No suicidal ideation or behaviour | Any non-suicidal self-injurious behavior | Suicidal Ideation | Preparatory action towards imminent suicidal | Not fatal suicide attempt | Completed suicide |
|---|
| Brexpiprazole and ADT | 25 | 0 | 1 | 0 | 0 | 0 |
Global Clinical Impression Severity of Illness (CGI-S) Score
Clinical Global Impression - Severity of Illness (CGI-S) The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients). (NCT01987960)
Timeframe: Period 2: Baseline to Week 12 (of randomized period)
| Intervention | Score (Mean) |
|---|
| Period 2 Absolute Mean at Baseline; Placebo and PAR/SER | 4.24 |
| Period 2 Absolute Mean at Baseline; Brexpiprazole and PAR/SER | 4.54 |
| Period 2 Absolute Mean at Week 12; Placebo and PAR/SER | 3.73 |
| Period 2 Absolute Mean at Week 12; Brexpiprazole and PAR/SER | 3.94 |
PTSD Symptoms Using CAPS-2 Total Score
Clinician-Administered PTSD Scale Part 2 (CAPS-2): 17 items in criteria B, C and D (Corresponding to CAPS-2) will be administered to provide a total score. They are rated on a 5 point scale for frequency from 0 (never or none) to 4 (daily or almost every day), and intensity from 0 (none) to 4 (extreme). The sum of the 17 items gives a toal score ranging from 0 to 136, with a higher score indicating greater symptom severity. (NCT01987960)
Timeframe: Period 2: Baseline to Week 12 (of randomized period)
| Intervention | Score (Mean) |
|---|
| Period 2 Absolute Mean at Baseline; Placebo and PAR/SER | 82.82 |
| Period 2 Absolute Mean at Baseline; Brexpiprazole and PAR/SER | 83.43 |
| Period 2 Absolute Mean at Week 12; Placebo and PAR/SER | 69.67 |
| Period 2 Absolute Mean at Week 12; Brexpiprazole and PAR/SER | 69.18 |
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." (NCT02012218)
Timeframe: Baseline and Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Group 1A | -12.8 |
| Group 1B | -18.4 |
| Group 2 | -19.5 |
| Group 3 | -19.2 |
| Group 4 | -16.8 |
Mean Change From Baseline in Delay and Probability Discounting Task (DPDT) Scores
The experiential discounting task (EDT) was a subject-completed computerized task designed to measure delay discounting, an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The participant chose between different amounts of money available at different delays or with different chances (probability to get the money). At the end of the session, one of the choices was selected at random, and the participant received whatever they chose in response of that question (immediate, delayed, or probabilistic amount). Formula for h-value: value = A / (1 + hO) p is probability of reward and O is odds against. The value of h indicates how the value of a reward and the probability of its occurrence decreases. The data are computerized and reflect delay discounting and impulsivity (higher discounting and higher probability discounting shows greater impulsivity). A total score is not computed for this task. (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | unitless (Mean) |
|---|
| Delay discounting task k value | Probability discouting task h value |
|---|
| Brexpiprazole | -3.586888 | 3.505900 |
Mean Change From Baseline in Go/No-Go Task for Mean Reaction Time
Executive function and working memory were assessed for the Go/No-go Task using computer-based and paper-pencil neuropsychological instruments. These instruments focused on measuring impulse inhibition. The instrument was administered at the following visits: Baseline and Week 6/ET. (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | milliseconds (Mean) |
|---|
| Mean reaction time (Go cues) | Mean reaction time (No-Go cues) |
|---|
| Brexpiprazole | -0.26 | -4.26 |
Mean Change From Baseline in Go/No-Go Task for P-inhibition Failures
Executive function and working memory were assessed for the Go/No-go Task using computer-based and paper-pencil neuropsychological instruments. These instruments focused on measuring impulse inhibition. The instrument was administered at the following visits: Baseline and Week 6/ET. (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | failures (Mean) |
|---|
| P-inhibition failures (Go cues) | P-inhibition failures (No-Go cues) |
|---|
| Brexpiprazole | -0.0193 | -0.0103 |
Percentage of Participants With CGI-I Response Rate
"The improvement of each participants condition was rated for each participant using the CGI-I. The study physician rated the participants total improvement whether or not it was due entirely to drug treatment. To perform this assessment, the study physician answered the following question: Compared to his/her condition at baseline, how much has the participant changed? Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared with the participants condition at Baseline prior to the first dose of study medication." (NCT02013531)
Timeframe: Week 1 to Week 6
| Intervention | percentage of participants (Number) |
|---|
| Week 1 | Week 2 | Week 3 | Week 4 | Week 6 |
|---|
| Brexpiprazole | 8.3 | 36.1 | 50.0 | 66.7 | 75.0 |
Mean Change From Baseline in Food Delay Discounting Task
"Delay discounting was a participant-completed task considered as an index of impulsive behavior. The participant chooses between a reward they could have today and another that they could get after a specified amount of time. The participant would not receive the rewards, but was asked to make decisions as though he or she were really going to receive them. AUC is defined as area under the concentration-time curve; AUC for food is presented below. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). To calculate the AUC, the X-axis is days, Y-axis is Food value, the actual area underneath the curve was calculated by summing the results for each delay and present value pair: x2 -x1[(y1 + y2)/2], where x1 and x2 are successive delays and y1 and y2 are the present values associated with those delays. The AUC can range from 1 (no discounting) to 0 (maximum discounting)." (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | unitless (Mean) |
|---|
| Brexpiprazole | 0.0371 |
Mean Change From Baseline in Barratt Impulsiveness Scale 11-item (BIS-11) Total Score
The BIS-11 was a participant-rated scale designed to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provided information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, non-planning impulsiveness, and attentional impulsiveness). The total score ranged from 30 to 120, with higher scores indicating impulsive personality traits. The BIS-11 was administered at the following visits: Baseline and Week 6/ET. (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | Units on a scale (Mean) |
|---|
| Brexpiprazole | -7.67 |
Mean Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score
The HAM-A was utilized for the evaluation of anxiety symptoms and was administered using the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A). Detailed instructions for administration of this structured interview were provided in the SIGH-A. The HAM-A was administered at the following visits: screening, Baseline, Weeks 1, 2, 3, 4, and 6/ET. HAM-A is a 14-item scale with each item is scored on a scale from 0 (not present) to 4 (very severe) with a total score of 0 to 56, with higher scores indicating severe anxiety symptoms. (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -17.80 |
Mean Change From Baseline in Hamilton Depression Rating Scale (HAM-D17) Total Score
The HAM-D17 was utilized as an assessment of a participants level of depression and was administered utilizing the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D). Detailed instructions for administration of this structured interview were provided in the SIGH-D. The HAM-D17 was administered at the following visits: screening, Baseline, and Week 6/ Early termination (ET). HAM-D17 is a 17-item questionnaire with a total score of 0 to 52 with higher scores indicating more depressive symptoms. (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | Units on a scale (Mean) |
|---|
| Brexpiprazole | -15.85 |
Mean Change From Baseline in Kellner Symptom Questionnaire (KSQ)
KSQ is a subject-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility and somatization. The questionnaire contains 92 items of which 68 items indicate symptoms and 24 items are antonyms of some of the symptoms that indicate well-being. The maximum score for each symptom subscale is 17, the well-being subscales 6 and for the total scale scores 23. A higher score indicates more distress than a lower score. The total subscale scores will be unevaluable if less than 19 of the 23 items are recorded. If 19 to 22 of the 23 items are recorded, the total subscale score is the mean of the recorded items multiplied by 23 and then rounded to the first decimal place. The total score will be unevaluable if less than 76 of the 92 items are recorded. If 76 to 91 of the 92 items and no less than 19 of the 23 items of each subscale are recorded, the total score will be the mean of the recorded items multiplied by 92 and then rounded to the first decimal place. (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | Units on a scale (Mean) |
|---|
| Brexpiprazole | -29.43 |
Mean Change From Baseline in Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score
The MGH-CPFQ was a participant-rated scale designed to assess cognitive and executive dysfunction including symptoms of fatigue in mood and anxiety disorders. The MGH-CPFQ consisted of 7 items, each rated on a scale from 1 (greater than normal functioning) to 6 (poorer than normal functioning). The total score of the 7 items ranged from 7 to 42, with higher scores indicative of a worse outcome. The MGH-CPFQ was administered at the following visits: Baseline and Week 6/ET. (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | Units on a scale (Mean) |
|---|
| Brexpiprazole | -9.85 |
Mean Change From Baseline in Money Delay Discounting Task
"Delay discounting was a participant-completed task considered as an index of impulsive behavior. The participant chose between a reward they could have today and another that they could get after a specified amount of time. The participant would not receive the rewards, but was asked to make decisions as though he or she were really going to receive them. AUC is defined as area under the concentration-time curve; AUC for money is presented below. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). To calculate the AUC, the X-axis is days, Y-axis is Money value, the actual area underneath the curve was calculated by summing the results for each delay and present value pair: x2 -x1[(y1 + y2)/2], where x1 and x2 are successive delays and y1 and y2 are the present values associated with those delays. The AUC can range from 1 (no discounting) to 0 (maximum discounting)." (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | unitless (Mean) |
|---|
| Brexpiprazole | 0.0707 |
Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Score
The SDS was a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. The SDS was a visual analogue scale that used spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the 3 domains. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0 = not at all to 10 = extremely. Scores of 5 and above were associated with significant functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | Units on a scale (Mean) |
|---|
| Brexpiprazole | -3.62 |
Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
"The MADRS is utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale 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. The possible Total scores are from 0 to 60, with higher values indicating worse outcome." (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -19.6 |
Mean Change From Baseline to Week 6 in the Number of Impulsive Choices in the Delayed Reward Task (DRT)
Delay discounting was a participant-completed task considered as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. During a training session, a single button with letter A or B appeared on the screen. The participant had to wait until the letter began to flash, and press the button only once. An amount of money was added to a counter and another single button appeared. During the test session, both buttons with letters A and B appeared on the screen. The participant had to choose one of the letters that remained; the other disappeared. The participant had to wait until the letter began to flash and then press the button again. An amount of money was added to the counter, and both letters appeared again. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). A total score was not calculated for this task. (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | Number of Impulsive Choices (Mean) |
|---|
| Brexpiprazole | 4.6 |
Mean Change in Clinical Global Impression-Severity (CGI-S) Total Score
"The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants." (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -2.2 |
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 6.
"The improvement of each participants condition was rated for each participant using the CGI-I. The study physician rated the participants total improvement whether or not it was due entirely to drug treatment. To perform this assessment, the study physician answered the following question: Compared to his/her condition at baseline, how much has the participant changed? Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared with the participants condition at Baseline prior to the first dose of study medication." (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | Units on a scale (Mean) |
|---|
| Brexpiprazole | 1.9 |
Percentage of Participants With a MADRS Remission
"MADRS remission rate, where remission is defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score from Baseline to Week 6. The MADRS consists of 10 items, all rated on a 0 to 6 scale 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. The possible Total scores are from 0 to 60, higher values indicate worse outcome." (NCT02013531)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|
| Brexpiprazole | 47.2 |
Percentage of Participants With a MADRS Response
"MADRS response rate, where response is defined as ≥ 50% reduction in respective total scores from Baseline to Week 6. The MADRS consists of 10 items, all rated on a 0 to 6 scale 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. The possible Total scores are from 0 to 60, higher values indicate worse outcome." (NCT02013531)
Timeframe: Week 6
| Intervention | Percentage of participants (Number) |
|---|
| Brexpiprazole | 69.4 |
Mean Change From Baseline in Delay Discounting Task - Monetary Choice Questionnaire (MCQ) Score
"Delay discounting was a participant-completed task is an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consists of 27 choices between immediate and delayed rewards. The participant chooses repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (for example, would you prefer $27 today or $50 in 21 days?) The answers provide an estimate of the participant's discounting rate; higher discounting rates indicate greater impulsivity. A total score is not computed for all 27 questions." (NCT02013531)
Timeframe: Baseline, Week 6
| Intervention | unitless (Mean) |
|---|
| Brexpiprazole | -0.008442 |
Mean Change From Baseline to Week 12 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score
"The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). Detailed instructions for administration of this structured interview was provided in the SIGMA. The MADRS consists of 10 items, all rated on a 0 to 6 scale 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. The possible Total scores are from 0 to 60." (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -18.1 |
Mean Change From Baseline to Week 12 in the Number of Impulsive Choices in the Delayed Reward Task (DRT)
Delay discounting was a participant-completed task considered as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. During a training session, a single button with letter A or B appeared on the screen. The participant had to wait until the letter began to flash, and press the button only once. An amount of money was added to a counter and another single button appeared. During the test session, both buttons with letters A and B appeared on the screen. The participant had to choose one of the letters that remained; the other disappeared. The participant had to wait until the letter began to flash and then press the button again. An amount of money was added to the counter, and both letters appeared again. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). A total score was not calculated for this task. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | Number of Impulsive Choices (Mean) |
|---|
| Brexpiprazole | 3.6 |
Percentage of Participants With MADRS Remission
MADRS remission rate, where remission is defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score from Baseline to Week 12. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | percentage of participants (Number) |
|---|
| Brexpiprazole | 42.6 |
Percentage of Participants With MADRS Response
MADRS response rate was defined as ≥ 50% reduction in respective total scores from Baseline to Week 12. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | percentage of particpants (Number) |
|---|
| Brexpiprazole | 53.2 |
Mean Change From Baseline to Week 12 in Go/No-Go Task (Mean Reaction Time)
Executive function and working memory were assessed for the Go/No-go Task using computer-based and paper-pencil neuropsychological instruments. These instruments focused on measuring impulse inhibition. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | milliseconds (Mean) |
|---|
| Mean reaction time (Go cues) | Mean reaction time (No-Go cues) |
|---|
| Brexpiprazole | -17.35 | -12.99 |
Mean Change From Baseline to Week 12 in Go/No-Go Task (P-inhibition Failure)
Executive function and working memory were assessed for the Go/No-go Task using computer-based and paper-pencil neuropsychological instruments. These instruments focused on measuring impulse inhibition. Proportions of inhibitory failures (p-inhibitory failures) is measured as the proportion of no-go targets in the go-cue condition in which a participant failed to inhibit a response. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | failures (Mean) |
|---|
| P-inhibition failures (Go cues) | P-inhibition failures (No-Go cues) |
|---|
| Brexpiprazole | 0.052 | 0.052 |
Mean Change From Baseline to Week 12 in Sheehan Disability Scale (SDS) Single Item Sub-scores
The SDS was a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. The SDS was a visual analogue scale that used spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the 3 domains. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0 = not at all to 10 = extremely. Scores of 5 and above were associated with significant functional impairment. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Work/ school | Social life | Family life/ home responsibilities |
|---|
| Brexpiprazole | -3.5 | -3.9 | -3.7 |
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 12
"The improvement of each participants condition was rated for each participant using the CGI-I. The study physician rated the participants total improvement whether or not it was due entirely to drug treatment. To perform this assessment, the study physician answered the following question: Compared to his/her condition at baseline, how much has the participant changed? Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared with the participants condition at Baseline prior to the first dose of study medication." (NCT02013609)
Timeframe: Weeks 1, 2, 3, 4, 5, 6, 8, 10 and 12
| Intervention | Units on a scale (Mean) |
|---|
| Week 1 (N= 46) | Week 2 (N= 47) | Week 3 (N= 47) | Week 4 (N= 47) | Week 6 (N= 47) | Week 8 (N= 47) | Week 10 (N= 47) | Week 12 (N= 47) |
|---|
| Brexpiprazole | 3.5 | 3.0 | 2.8 | 2.7 | 2.6 | 2.5 | 2.3 | 2.2 |
Number of Participants With CGI-I Response
The CGI-I response rate was defined as a CGI-I score of 1 (very much improved) or 2 (much improved). (NCT02013609)
Timeframe: Weeks 1, 2, 3, 4, 6, 8 ,10 and 12
| Intervention | participants (Number) |
|---|
| Week 1 (N= 46) | Week 2 (N= 47) | Week 3 (N= 47) | Week 4 (N= 47) | Week 6 (N= 47) | Week 8 (N= 47) | Week 10 (N= 47) | Week 12 (N= 47) |
|---|
| Brexpiprazole | 4 | 12 | 17 | 24 | 27 | 29 | 28 | 30 |
Mean Change From Baseline to Week 12 in Delay and Probability Discounting Task (DPDT)
The experiential discounting task (EDT) was a subject-completed computerized task designed to measure delay discounting, an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The participant chose between different amounts of money available at different delays or with different chances (probability to get the money). At the end of the session, one of the choices was selected at random, and the participant received whatever they chose in response of that question (immediate, delayed, or probabilistic amount). Formula for h-value:value = A / (1 + hO) p is probability of reward and O is odds against.The value of h indicates how the value of a reward and the probability of its occurrence decreases.The data are computerized and reflect delay discounting and impulsivity (higher discounting and higher probability discounting shows greater impulsivity). A total score is not computed for this task. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | unitless (Mean) |
|---|
| Delay Discounting Task k value | Delay Discounting Task h value |
|---|
| Brexpiprazole | 21.315241 | 10.350419 |
Mean Change From Baseline in Delay Discounting Task - Monetary Choice Questionnaire (MCQ) k Value
"Delay discounting was a participant-completed task is an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consists of 27 choices between immediate and delayed rewards. The participant chooses repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (for example, would you prefer $27 today or $50 in 21 days?) The answers provide an estimate of the participant's discounting rate; higher discounting rates indicate greater impulsivity. A total score is not computed for all 27 questions." (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | unitless (Mean) |
|---|
| Brexpiprazole | 0.009531 |
Mean Change From Baseline in Food Delay Discounting Task (DDT)
"Delay discounting was a participant-completed task considered as an index of impulsive behavior. The participant chooses between a reward they could have today and another that they could get after a specified amount of time. The participant would not receive the rewards, but was asked to make decisions as though he or she were really going to receive them. AUC is defined as area under the concentration-time curve; AUC for food is presented below. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). To calculate the AUC, the X-axis is days, Y-axis is Food value, the actual area underneath the curve was calculated by summing the results for each delay and present value pair: x2 -x1[(y1 + y2)/2], where x1 and x2 are successive delays and y1 and y2 are the present values associated with those delays. The AUC can range from 1 (no discounting) to 0 (maximum discounting)." (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | unitless (Mean) |
|---|
| Brexpiprazole | 0.3487 |
Mean Change From Baseline in Money Delay Discounting Task
"Delay discounting was a participant-completed task considered as an index of impulsive behavior. The participant chose between a reward they could have today and another that they could get after a specified amount of time. The participant would not receive the rewards, but was asked to make decisions as though he or she were really going to receive them. AUC is defined as area under the concentration-time curve; AUC for money is presented below. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). To calculate the AUC, the X-axis is days, Y-axis is Money value, the actual area underneath the curve was calculated by summing the results for each delay and present value pair: x2 -x1[(y1 + y2)/2], where x1 and x2 are successive delays and y1 and y2 are the present values associated with those delays. The AUC can range from 1 (no discounting) to 0 (maximum discounting)." (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | unitless (Mean) |
|---|
| Brexpiprazole | -0.0095 |
Mean Change From Baseline to Week 12 in Barratt Impulsiveness Scale 11-Item (BIS-11) Total Score
The BIS-11 was a participant-rated scale designed to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provided information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, non-planning impulsiveness, and attentional impulsiveness). The total score ranged from 30 to 120, with higher scores indicating impulsive personality traits. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -7.1 |
Mean Change From Baseline to Week 12 in Clinical Global Impression-Severity (CGI-S) Total Score
"The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants." (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -2.0 |
Mean Change From Baseline to Week 12 in Hamilton Depression Rating Scale (HAM-D17) Total Score
The HAM-D17 was utilized as an assessment of a participants level of depression and was administered utilizing the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D). Detailed instructions for administration of this structured interview were provided in the SIGH-D. HAM-D17 is a 17-item questionnaire with a total score of 0 to 52 with higher scores indicating more depressive symptoms. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -14.9 |
Mean Change From Baseline to Week 12 in Kellner Symptom Questionnaire (KSQ) Total Score
KSQ is a subject-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility and somatization. The questionnaire contains 92 items of which 68 items indicate symptoms and 24 items are antonyms of some of the symptoms that indicate well-being. The maximum score for each symptom subscale is 17, the well-being subscales 6 and for the total scale scores 23.The total subscale scores will be unevaluable if less than 19 of the 23 items are recorded. If 19 to 22 of the 23 items are recorded, the total subscale score is the mean of the recorded items multiplied by 23 and then rounded to the first decimal place. The total score will be unevaluable if less than 76 of the 92 items are recorded. If 76 to 91 of the 92 items and no less than 19 of the 23 items of each subscale are recorded, the total score will be the mean of the recorded items multiplied by 92 and then rounded to the first decimal place. A higher score indicates more distress than a lower score. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -30.5 |
Mean Change From Baseline to Week 12 in Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score
The MGH-CPFQ was a participant-rated scale designed to assess cognitive and executive dysfunction including symptoms of fatigue in mood and anxiety disorders. The MGH-CPFQ consisted of 7 items, each rated on a scale from 1 (greater than normal functioning) to 6 (poorer than normal functioning). The total score of the 7 items ranged from 7 to 42. (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -8.1 |
Mean Change From Baseline to Week 12 in Sheehan Disability Scale (SDS) 3-item Total/Summed Score
The SDS was a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. The SDS was a visual analogue scale that used spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the 3 domains. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0 = not at all to 10 = extremely. Scores of 5 and above were associated with significant functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -3.74 |
Mean Change From Baseline to Week 12 in Social Adaptation Self-evaluation Scale (SASS) Total Score
The SASS was a self-rated instrument to assess the social motivation and behavior in participants with depression. It contained 21 items covering the different aspects of social interactions, global social attitude, and self-perception. The SASS total score will be un-evaluable if less than 16 of the 20 items (for item number 1 and item number 2, participant is to answer either one of these) are recorded. If 16 to 19 of the 20 items are recorded, the SASS total score will be the mean of the recorded items multiplied by 20 and then rounded to the first decimal place.Each item is scored from 0 to 3, corresponding to minimal and maximal social adjustment, with a total score range of 0 to 60 (higher scores, indicating worse outcome). (NCT02013609)
Timeframe: Baseline and Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | 9.7 |
Mean Change From Baseline to Week 16 in Delay Discounting Task - Monetary Choice Questionnaire (MCQ) Scores
"Delay discounting was a participant-completed task is an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consists of 27 choices between immediate and delayed rewards. The participant chooses repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (for example, would you prefer $27 today or $50 in 21 days?) The answers provide an estimate of the participant's discounting rate; higher discounting rates indicate greater impulsivity. A total score is not computed for all 27 questions." (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | unitless (Mean) |
|---|
| Brexpiprazole | 0.008520 |
Mean Change From Baseline to Week 16 in Food Delay Discounting Task
"Delay discounting was a participant-completed task considered as an index of impulsive behavior. The participant chooses between a reward they could have today and another that they could get after a specified amount of time. The participant would not receive the rewards, but was asked to make decisions as though he or she were really going to receive them. AUC is defined as area under the concentration-time curve; AUC for food is presented below. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). To calculate the AUC, the X-axis is days, Y-axis is Food value, the actual area underneath the curve was calculated by summing the results for each delay and present value pair: x2 -x1[(y1 + y2)/2], where x1 and x2 are successive delays and y1 and y2 are the present values associated with those delays. The AUC can range from 1 (no discounting) to 0 (maximum discounting)." (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | unitless (Mean) |
|---|
| Brexpiprazole | 0.037 |
Mean Change From Baseline to Week 16 in Money Delay Discounting Task
"Delay discounting was a participant-completed task considered as an index of impulsive behavior. The participant chose between a reward they could have today and another that they could get after a specified amount of time. The participant would not receive the rewards, but was asked to make decisions as though he or she were really going to receive them. AUC is defined as area under the concentration-time curve; AUC for money is presented below. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). To calculate the AUC, the X-axis is days, Y-axis is Money value, the actual area underneath the curve was calculated by summing the results for each delay and present value pair: x2 -x1[(y1 + y2)/2], where x1 and x2 are successive delays and y1 and y2 are the present values associated with those delays. The AUC can range from 1 (no discounting) to 0 (maximum discounting)." (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | unitless (Mean) |
|---|
| Brexpiprazole | 0.001 |
Mean Change From Baseline to Week 16 in Pittsburgh Sleep Quality Index (PSQI) Total Score
"The PSQI was a self-rated questionnaire that assessed sleep quality and disturbances over a 1-month time interval. Seven domains were measured: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction over the last month. The PSQI contains 19 self-rated questions and 5 questions rated by the bed partner or roommate (if 1 is available). Only self-rated questions are included in the scoring.The 19 self-rated items are combined to form 7 component scores, each of which has a range of 0 - 3 points. In all cases, a score of 0 indicates no difficulty, while a score of 3 indicates severe difficulty. The 7 component scores are then added to yield 1 global score, with a range of 0 - 21 points, 0 indicating no difficulty and 21 indicating severe difficulties in all areas." (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -1.8 |
Mean Change From Baseline to Week 16 in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -10.2 |
Mean Change From Baseline to Week 16 in Delay and Probability Discounting Task (DPDT) - Experiential Discounting Task Scores
Delay discounting measures the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ with completion of an Experiential Discounting task (EDT). The participant chose between different amounts of money available at different delays or with different chances (probability to get the money). At the end of the session, one of the choices was selected at random, and the participant received whatever they chose in response of that question (immediate, delayed, or probabilistic amount). Formula for h-value:value = A / (1 + hO) p is probability of reward and O is odds against.The value of h indicates how the value of a reward and the probability of its occurrence decreases. The data are computerized and reflect delay discounting and impulsivity (higher discounting and higher Probability discounting shows greater impulsivity). A total score is not computed for this task. (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | unitless (Mean) |
|---|
| Delay Discounting Task k value | Probability Discounting Task h value |
|---|
| Brexpiprazole | -103.167142 | 2.866008 |
Mean Change From Baseline to Week 16 in Specific Levels of Functioning (SLOF) Total Score
The SLOF questionnaire used in this trial consists of 30 items grouped into 4 areas: social functioning, social acceptability, activities, and work skill. The SLOF scale correlates with a participant's quality of life. Total SLOF scale is sum of these 4 areas score. Each of the questions in the above domains is rated on a 5-point Likert scale. Scores on the instrument range from 30 to 150 with higher scores indicating the better the overall functioning of the patient. (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | 13.1 |
Mean Change From Baseline to Week 16 Scores of the Following Negative Scale Items: Active Social Avoidance, Emotional Withdrawal, Passive/Apathetic Social Withdrawal, and Difficulty in Abstract Thinking
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -2.0 |
CGI-I Response Rate
The CGI-I response rate was defined as percentage of participants with CGI-I score of 1 (very much improved) or 2 (much improved). (NCT02013622)
Timeframe: Weeks 4, 8, 12, and 16
| Intervention | percentage of participants (Number) |
|---|
| Week 4 | Week 8 | Week 12 | Week 16 |
|---|
| Brexpiprazole | 39.6 | 35.4 | 41.7 | 41.7 |
Mean Clinical Global Impression-Improvement (CGI-I) Score
"The improvement of each participants condition was rated for each participant using the CGI-I. The study physician rated the participants total improvement whether or not it was due entirely to drug treatment. To perform this assessment, the study physician answered the following question: Compared to his/her condition at baseline, how much has the participant changed? Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared with the participants condition at Baseline prior to the first dose of study medication." (NCT02013622)
Timeframe: Week 1 to Week 16
| Intervention | Units on a scale (Mean) |
|---|
| Week 1 | Week 2 | Week 3 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 14 | Week 16 |
|---|
| Brexpiprazole | 3.6 | 3.1 | 2.7 | 2.8 | 2.7 | 2.9 | 2.8 | 2.8 | 2.9 | 2.8 |
Mean Change From Baseline to Week 16 in Treatment Satisfaction Questionnaire for Medication (TSQM) Total Score
"The TSQM-14 was a participant-rated scale used to assess subjective satisfaction with medication. The TSQM-14 provided scores on 4 domains: effectiveness (questions 1 to 3) side effects (4 to 8), convenience (9 to 11), and global satisfaction (12 to 14). The effectiveness domain was rated on a 7-point scale from extremely satisfied to extremely dissatisfied. The side effects domain provided an option to skip questions 5 to 8 if the subject provided a negative response to item number 4, ie, As a result of taking this medication, do you currently experience any side effects at all? Scores for each domain were transformed into a final score ranging from 0 to 100, with higher numbers indicating a higher level of satisfaction." (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Effectiveness | Side effects | Convenience | Global satisfaction |
|---|
| Brexpiprazole | 20.00 | 10.25 | 11.83 | 20.67 |
Mean Change From Baseline to Week 16 in Go/No-Go Task (P-inhibition Failures)
Executive function and working memory were assessed using computer based neuropsychological instruments at Baseline and Week 16/Early Termination (ET). These instruments focused on measuring impulse inhibition. Proportions of inhibitory failures (p-inhibitory failures) is measured as the proportion of no-go targets in the go-cue condition in which a participant failed to inhibit a response. (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | failures (Mean) |
|---|
| p-inhibition failures (go cues) | p-inhibition failures (no-go cues) |
|---|
| Brexpiprazole | 0.045 | 0.066 |
Mean Change From Baseline to Week 16 in Go/No-Go Task (Mean Reaction Time)
Executive function and working memory were assessed using computer based neuropsychological instruments at Baseline and Week 16/Early Termination (ET). These instruments focused on measuring impulse inhibition. (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | milliseconds (Mean) |
|---|
| Mean reaction time (go cues) | Mean reaction time (no-go cues) |
|---|
| Brexpiprazole | -2.05 | -18.77 |
Change From Baseline to Week 16 in the Mean Number of Impulsive Choices in the Delayed Reward Task (DRT)
Delay discounting was a participant-completed task considered as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. During a training session, a single button with letter A or B appeared on the screen. The participant had to wait until the letter began to flash, and press the button only once. An amount of money was added to a counter and another single button appeared. During the test session, both buttons with letters A and B appeared on the screen. The participant had to choose one of the letters that remained; the other disappeared. The participant had to wait until the letter began to flash and then press the button again. An amount of money was added to the counter, and both letters appeared again. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). A total score was not calculated for this task. (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | Number of Impulsive Choices (Mean) |
|---|
| Brexpiprazole | 8.9 |
Mean Change From Baseline to Week 16 in Barratt Impulsiveness Scale (BIS) 11-Item
The BIS-11 was a participant-rated scale designed to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provided information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, non-planning impulsiveness, and attentional impulsiveness). The total score ranged from 30 to 120, with higher scores indicating impulsive personality traits. It took 10 to 15 minutes to complete the BIS-11. The BIS-11 was administered at the following visits: Baseline and Week 16/ET. (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | Units on a scale (Mean) |
|---|
| Brexpiprazole | -4.8 |
Mean Change From Baseline to Week 16 in Clinical Global Impression-Severity (CGI-S) Score
"The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants." (NCT02013622)
Timeframe: Baseline and Week 16
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -0.6 |
Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score
"The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants." (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -1.6 |
| Aripiprazole | -1.3 |
Change From Baseline to Week 6 in Specific Levels of Functioning Scale (SLOF) Total Score
"The SLOF questionnaire used in this trial consisted of 30 items grouped into 4 areas: interpersonal relationships, social acceptability, activities, and work skill. The SLOF correlates with a subject's quality of life. Each of the questions in the domains is rated on a 5-point Likert scale ranging from 1 not well at all to 5 very well. The possible total score range for SLOF is from 30 to 150, higher score indicating better overall functioning of the participant." (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | 7.5 |
| Aripiprazole | 6.0 |
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -22.9 |
| Aripiprazole | -19.4 |
Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11 Item) Total Score
The BIS-11, a subject-rated scale designed to assess impulsive personality traits, was administered at the baseline and Week 6 visits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provided information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, nonplanning impulsiveness, and attentional impulsiveness). The total score ranged from 30 to 120, higher scores indicate better personality trait. (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -2.6 |
| Aripiprazole | -0.1 |
Change From Baseline in Cognitive Test Battery Scores of Identification Task
The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | z-score (Least Squares Mean) |
|---|
| Brexpiprazole | -0.002 |
| Aripiprazole | -0.011 |
Change From Baseline in Cognitive Test Battery Scores of Groton Maze Learning (GML)
The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | z-score (Least Squares Mean) |
|---|
| Brexpiprazole | 0.7 |
| Aripiprazole | -4.6 |
Change From Baseline in Cognitive Test Battery Scores of Detection Task
The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | z-score (Least Squares Mean) |
|---|
| Brexpiprazole | 0.024 |
| Aripiprazole | -0.029 |
Change From Baseline in Cognitive Test Battery of Early Phase Battery Score
The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. The cognitive test early phase battery was analyzed; tasks included Groton Maze Learning Task, Detection Task, Identification Task, and One Card Learning Task. (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | z-score (Least Squares Mean) |
|---|
| Brexpiprazole | -0.010 |
| Aripiprazole | 0.113 |
Change From Baseline in Cognitive Test Battery Composite Score
The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | z-score (Least Squares Mean) |
|---|
| Brexpiprazole | 0.045 |
| Aripiprazole | -0.024 |
Change From Baseline in Cognitive Test Battery Scores of One Card Learning Task
The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | z-score (Least Squares Mean) |
|---|
| Brexpiprazole | 0.003 |
| Aripiprazole | 0.000 |
Response Rate by Study Week
The response rate was defined as reduction of ≥30% from Baseline in PANSS Total Score or CGI-I score of of 1 (very much improved) or 2 (much improved). (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | percentage of participants (Number) |
|---|
| Brexpiprazole | 60.9 |
| Aripiprazole | 48.5 |
Mean Change in Clinical Global Impression-Improvement (CGI-I) Score at Week 6
The efficacy of trial medication was rated for each participant using the CGI-I. The study physician would rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at Baseline prior to the first dose of double-blind study medication. Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. (NCT02054702)
Timeframe: Baseline to Week 6
| Intervention | Units on a scale (Mean) |
|---|
| Brexpiprazole | 2.5 |
| Aripiprazole | 2.7 |
Change From Baseline to Week 6 in Stop Signal Reaction Time Task (SSRT) Task Behavior
Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (<)/right (>) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 & 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes & 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with & without a response (NCT02194933)
Timeframe: At baseline (Day 0), and Week 6 (Day 42).
| Intervention | Millisecond (Mean) |
|---|
| At Week 0 | At Week 6 |
|---|
| Brexpiprazole 2 mg | 357.63 | 299.68 |
,| Brexpiprazole 4 mg | 323.25 | 302.57 |
Change From Baseline to Week 6 in Go/No-go Task Behavior
Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go). (NCT02194933)
Timeframe: At baseline (Day 0), week 6 (Day 42) of the treatment phase
| Intervention | Millisecond (Mean) |
|---|
| At Week 0 | At Week 6 |
|---|
| Brexpiprazole 2 mg | 0.11 | 0.08 |
,| Brexpiprazole 4 mg | 0.09 | 0.12 |
Change From Baseline to Week 3 in SSRT Task Behavior
Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (<)/right (>) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 & 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes & 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with & without a response (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 3 (Day 21).
| Intervention | Millisecond (Median) |
|---|
| At week 0 | At week 3 |
|---|
| Brexpiprazole 2 mg | 357.63 | 337.62 |
,| Brexpiprazole 4 mg | 323.25 | 328.05 |
Change From Baseline to Week 3 in Go/No-go Task Behavior
Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go). (NCT02194933)
Timeframe: At baseline (Day 0), and week 3 (Day 21) of the treatment phase
| Intervention | Millisecond (Mean) |
|---|
| Week 0 | Week 3 |
|---|
| Brexpiprazole 2 mg | 0.11 | 0.10 |
,| Brexpiprazole 4 mg | 0.09 | 0.15 |
Clinical Global Impression - Improvement Scale (CGI-I) Score at Week 6
To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP). (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 6 (Day 42).
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole 2 mg | 3.6 |
| Brexpiprazole 4 mg | 3.9 |
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms. (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 6 (Day 42).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -2.4 |
| Brexpiprazole 4 mg | -4.1 |
Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score
The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 6 (Day 42).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -0.1 |
| Brexpiprazole 4 mg | 0.0 |
Change From Baseline to Week 3 in BIS-11
A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11. (NCT02194933)
Timeframe: At baseline (Day 0), and Week 3 (Day 21) of the treatment.
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -2.4 |
| Brexpiprazole 4 mg | -2.3 |
CGI-I Score at Week 3
To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP). (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 3 (Day 21).
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole 2 mg | 3.7 |
| Brexpiprazole 4 mg | 3.8 |
Change From Baseline to Week 6 in PANSS Positive Subscale Score
PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity. (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 6 (Day 42).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -1.4 |
| Brexpiprazole 4 mg | -1.3 |
Change From Baseline to Week 6 in PANSS Negative Subscale Score
PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity. (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 6 (Day 42).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -0.9 |
| Brexpiprazole 4 mg | 0.2 |
Change From Baseline to Week 6 in Monetary Choice Questionnaire (MCQ) Score
"To measure delay discounting as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity. It took 5 to10 minutes to complete the MCQ" (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 6 (Day 42).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -0.019762 |
| Brexpiprazole 4 mg | 0.023685 |
Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11)
A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11. (NCT02194933)
Timeframe: At baseline (Day 0), and Week 6 (Day 42) of the treatment.
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -2.6 |
| Brexpiprazole 4 mg | 1.0 |
Change From Baseline to Week 3 in PANSS Total Score
The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms. (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 3 (Day 21).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -2.0 |
| Brexpiprazole 4 mg | -2.3 |
Change From Baseline to Week 3 in PANSS Positive Subscale Score
PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity. (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 3 (Day 21).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -1.2 |
| Brexpiprazole 4 mg | -1.3 |
Change From Baseline to Week 3 in PANSS Negative Subscale Score
PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity. (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 3 (Day 21).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | 0.2 |
| Brexpiprazole 4 mg | 0.8 |
Change From Baseline to Week 3 in MCQ Score
"To measure delay discounting as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity." (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 3 (Day 21).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -0.012073 |
| Brexpiprazole 4 mg | 0.014520 |
Change From Baseline to Week 3 in CGI-S Score
The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 3 (Day 21).
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | -0.3 |
| Brexpiprazole 4 mg | -0.1 |
Change From Baseline to Week 3 in CPT Behavior
"The AX trials were target trials with a valid cue followed by a valid probe X. This feature was intended to encourage participants to expect a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with target responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the Yes button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial." (NCT02194933)
Timeframe: During trial visits from Day 0 to Week 3 (Day 21).
| Intervention | Rate of correct response (Least Squares Mean) |
|---|
| Brexpiprazole 2 mg | 1.79 |
| Brexpiprazole 4 mg | -0.61 |
Change in the Sheehan Disability Scale (SDS) From Baseline to End of Treatment
To assess the change in the Sheehan Disability Scale (SDS) Score (the mean of 3 individual item scores) from Baseline (End of Phase A [Week 8]) to Week 14 (End of Phase B). SDS was a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life, and family life/home responsibility. Each item was scored using a scale of 0 to 10 (a higher score indicates symptoms have disrupted work, social life, and family life/home responsibility extremely). The maximum total score was 30; 0 = not at all, to 30 = extremely. (NCT02196506)
Timeframe: From baseline (end of Phase A [Week 8]) to week 14
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole + ADT | -1.63 |
| Placebo + ADT | -1.41 |
Change From End of Phase A to End of Phase B in MADRS Total Score for the Subpopulation With <25% Improvement From Baseline of Phase A to End of Phase A in MADRS Total Score
To assess the change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in MADRS Total Score for the subpopulation with < 25% improvement from baseline of Phase A (Week 0) to end of Phase A (Week 8) in MADRS Total Score. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected. (NCT02196506)
Timeframe: From baseline (end of Phase A [Week 8]) to week 14
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole + ADT | -11.1 |
| Placebo + ADT | -8.87 |
Change From End of Phase A to End of Phase B in MADRS Total Score for the Subpopulations With Anxious Distress as Specified in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).
To assess the change from end of Phase A (Week 8) to end of Phase B (Week 14) in MADRS Total Score for the subpopulations with anxious distress as specified in DSM-V. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected. (NCT02196506)
Timeframe: From baseline (end of Phase A [Week 8]) to week 14
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole + ADT | -11.8 |
| Placebo + ADT | -8.87 |
Change in the Montgomery-Asberg Depression
To assess the change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score from Baseline (End of Phase A [Week 8]) to Week 14. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The rater decided whether the rating lied on predefined scale steps (0, 2, 4, 6) or between them (1, 3, 5). The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected. (NCT02196506)
Timeframe: From baseline (end of Phase A [Week 8]) to week 14
| Intervention | Units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole + ADT | -10.4 |
| Placebo + ADT | -8.07 |
Number of Patients With Treatment-Emergent Adverse Events
Treatment-emergent adverse event is an adverse event that started or increased in intensity at or after baseline visit (NCT02400346)
Timeframe: Baseline to 30 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Adjunct Brexpiprazole | 102 |
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞) of OPC-34712
To evaluate AUC∞ of OPC-34712 4-mg ODT formulation relative to 4-mg conventional tablet formulation (NCT02875080)
Timeframe: Predose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96, 120，144, 168, 216, 264, and 312 hours postdose
| Intervention | ng·h/mL (Mean) |
|---|
| OPC-34712 Disintegrating Tablet With Water | 2920 |
| OPC-34712 Disintegrating Tablet Without Water | 2830 |
| OPC-34712 Conventional Tablet With Water | 2770 |
Maximum Plasma Concentration (Cmax) of OPC-34712
To evaluate Cmax of OPC-34712 4-mg ODT formulation relative to 4-mg conventional tablet formulation (NCT02875080)
Timeframe: Predose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96, 120，144, 168, 216, 264, and 312 hours postdose
| Intervention | ng/mL (Mean) |
|---|
| OPC-34712 Disintegrating Tablet With Water | 47.4 |
| OPC-34712 Disintegrating Tablet Without Water | 44.9 |
| OPC-34712 Conventional Tablet With Water | 46.1 |
Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score
CAPS-5:clinician-rated, structured interview to assess PTSD diagnostic status, symptoms severity as defined by DSM-5. CAPS-5 Past Week version of scale was completed at Baseline and at all visits after Baseline. CAPS-5 was calculated by summing severity scores for 20 DSM-5 PTSD symptoms (items 1-20) from categories: Category B:Intrusion symptoms (5 items); Category C:Avoidance symptoms (2 items); Category D:Cognition and mood symptoms (7 items); Category E:Arousal and reactivity symptoms (6 items). CAPS-5 total score was imputed by adding all subscores from categories B,C,D,E. Each symptom was scored 0 (Absent) to 4 (Extreme/incapacitating), to yield a score with range 0-80. Higher scores=worse outcome. Mixed model repeated measure (MMRM) was used for analysis. (NCT03033069)
Timeframe: Baseline, Week 12
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Brexpiprazole + Sertraline | -16.4 |
| Brexpiprazole | -12.2 |
| Sertraline | -11.4 |
| Placebo | -10.5 |
Safety and Tolerability Outcomes: 12-lead Electrocardiogram (ECG) - Number of Participants With Abnormal ECGs
Electrocardiograms (ECGs) were conducted at baseline, and follow-up visits conducted 5, 8, 11, 14, and 21 days after baseline. Any found to be abnormal were evaluated by a clinician as to the clinical significance of the ECG abnormality. (NCT03149991)
Timeframe: ECGs were conducted at baseline and 5, 8, 11, 14, and 21 days after baseline
| Intervention | participants (Number) |
|---|
| # of participants with abnormal ECGs, Baseline | # of participants with abnormal ECGs, Day 5 | # of participants with abnormal ECGs, Day 8 | # of participants with abnormal ECGs, Day 11 | # of participants with abnormal ECGs, Day 14 | # of participants with abnormal ECGs, Day 21 |
|---|
| Ketamine/Brexpiprazole Arm | 12 | 9 | 11 | 10 | 10 | 8 |
,| Ketamine/Placebo Arm | 9 | 9 | 12 | 10 | 7 | 9 |
Change From Baseline on Symptoms of Depression Questionnaire (SDQ)
"Superiority will be demonstrated by a statistically significant greater decrease (p<0.05, 2 sided) on the SDQ total score for participants receiving brexpiprazole versus placebo therapy.~Symptoms of Depression Questionnaire (SDQ): This validated self-rating instrument has 44 items on a scale of 1-6, measuring multiple depressive symptom domains, with higher scores indicating worse depression symptoms. Participants reported on their experiences over the past three days." (NCT03149991)
Timeframe: SDQ was assessed on Days 0, 1, 2, 5, 8, 11, 14, 17, 21, 23, 28
| Intervention | score on a scale (Mean) |
|---|
| SDQ, Day 0 | SDQ, Day 1 | SDQ, Day 2 | SDQ, Day 5 | SDQ, Day 8 | SDQ, Day 11 | SDQ, Day 14 | SDQ, Day 17 | SDQ, Day 21 | SDQ, Day 23 | SDQ, Day 28 |
|---|
| Ketamine/Brexpiprazole Arm | 3.7 | 3.5 | 3.5 | 3.4 | 3.3 | 3.1 | 3.0 | 3.1 | 3.0 | 2.8 | 2.9 |
,| Ketamine/Placebo Arm | 3.7 | 3.5 | 3.3 | 3.3 | 3.2 | 3.1 | 3.2 | 3.2 | 3.2 | 3.0 | 3.0 |
Safety and Tolerability Outcomes: Treatment-emergent Adverse Events (Number of Participants Reporting)
Adverse events were recorded on a rolling basis from screening until the last day of the study (i.e., Day 28). For patients who reported any AEs, the average number of AEs per person per group were recorded. Site investigators rated whether AEs were possibly or probably related to treatment. (NCT03149991)
Timeframe: Adverse events were recorded on a rolling basis from screening through Day 28
| Intervention | Participants (Count of Participants) |
|---|
| Ketamine/Brexpiprazole Arm | 17 |
| Ketamine/Placebo Arm | 18 |
Safety and Tolerability Outcomes: Treatment-emergent Adverse Events (Average Number Per Person Per Group)
Adverse events were recorded on a rolling basis from screening until the last day of the study (i.e., Day 28). For patients who reported any adverse events, the mean number of adverse events per person per group were calculated and are reported below. (NCT03149991)
Timeframe: The outcome was recorded on a rolling basis from screening through Day 28
| Intervention | Adverse events (Mean) |
|---|
| Ketamine/Brexpiprazole Arm | 3.8 |
| Ketamine/Placebo Arm | 3.6 |
Long-term Sustained Response, as Measured by Achieving a 50% Reduction on the Montgomery-Asberg Depression Rating Scale (MADRS) on Day 28 (Number and Percentage of Participants Achieving Sustained Response Reported)
The table below compares percentages of participants in each arm who achieved a 50% or greater reduction on the Montgomery-Asberg Depression Rating Scale (MADRS) on Day 28 compared with baseline. This 10- item clinician-rated instrument measures depression severity with higher scores indicating more severity. Each item can be scored from 0 to 6 for a total sore range of 0 to 60. It was administered with a structured interview guide. Experiences over the past 3 days were rated. (NCT03149991)
Timeframe: MADRS was assessed on Days 0, 2, 3, 8, 11, 14, 17, 21, 23, 28; 50% reduction compared Day 28 to Baseline.
| Intervention | Participants (Count of Participants) |
|---|
| Ketamine/Brexpiprazole Arm | 10 |
| Ketamine/Placebo Arm | 8 |
Safety and Tolerability Outcomes: Number of Participants With Abnormal Vital Signs (Elevated Heart Rate)
Heart rate was measured during each administration of ketamine, occurring on days 0, 5, 8, 11, 14, and 21. This vital sign was measured 6 times following the intranasal administration of ketamine: 15 minutes post dose, 30 minutes post dose, 45 minutes post dose, 1 hour post dose, 90 minutes post dose, and 2 hours post dose. Average heart rate per group was assessed. Medical staff monitoring the ketamine administration were prepared to treat heart rate greater than 110 bpm, or follow their institutional guidelines if more conservative, if these elevations did not resolve spontaneously within a short time period. Data presented are number of participants with elevated heart rate at any of the listed time points. (NCT03149991)
Timeframe: Heart rate was measured during each administration of ketamine, occurring on days 0, 5, 8, 11, 14, and 21.
| Intervention | Participants (Count of Participants) |
|---|
| Ketamine/Brexpiprazole Arm | 1 |
| Ketamine/Placebo Arm | 1 |
Safety and Tolerability Outcomes: Suicidal Ideation and Behavior
The clinician rated behavioral module of the Concise Health Risk Tracking (CHRT) scale was used at each study visit to identify suicidal ideation and behavior. The first item assesses suicidal ideation. All subsequent items assess suicidal behavior. The below table is for Item 1. (NCT03149991)
Timeframe: The CHRT was used at each study visit through Day 28
| Intervention | Participants (Count of Participants) |
|---|
| Suicidal Ideation-Screening | Suicidal Ideation-Baseline | Suicidal Ideation-Day 1 | Suicidal Ideation-Day 2 | Suicidal Ideation-Day 5 | Suicidal Ideation-Day 8 | Suicidal Ideation-Day 11 | Suicidal Ideation-Day 14 | Suicidal Ideation-Day 17 | Suicidal Ideation-Day 21 | Suicidal Ideation-Day 23 | Suicidal Ideation-Day 28 |
|---|
| Ketamine/Brexpiprazole Arm | 9 | 4 | 5 | 5 | 5 | 5 | 3 | 5 | 4 | 4 | 2 | 2 |
,| Ketamine/Placebo Arm | 4 | 4 | 5 | 2 | 7 | 8 | 3 | 3 | 2 | 3 | 4 | 4 |
Safety and Tolerability Outcomes: Number of Participants With Abnormal Laboratory Test Results
Chemistry and CBC laboratory tests were obtained during the screening visit and on Day 14 and 28 follow-ups. If a test result was abnormal (i.e., outside of the site-specific pre-specified range of expected values), it was evaluated by a clinician as to its clinical significance. (NCT03149991)
Timeframe: Chemistry and CBC laboratory tests were obtained during screening and on Day 14 and 28 follow-ups
| Intervention | Participants (Count of Participants) |
|---|
| Abnormal lab results at Screening | Abnormal lab results at Day 14 | Abnormal lab results at Day 28 |
|---|
| Ketamine/Brexpiprazole Arm | 1 | 1 | 1 |
,| Ketamine/Placebo Arm | 2 | 0 | 0 |
Safety and Tolerability Outcomes: 12-lead Electrocardiogram (ECG) - Total Number of Abnormal ECGs
Electrocardiograms (ECGs) were conducted at baseline, and follow-up visits conducted 5, 8, 11, 14, and 21 days after baseline. Any found to be abnormal were evaluated by a clinician as to the clinical significance of the ECG abnormality. (NCT03149991)
Timeframe: ECGs were conducted at baseline and 5, 8, 11, 14, and 21 days after baseline
| Intervention | Number of abnormal ECGs (Number) |
|---|
| Ketamine/Brexpiprazole Arm | 60 |
| Ketamine/Placebo Arm | 56 |
Safety and Tolerability Outcomes: Number of Participants With Abnormal Vital Signs (Elevated Blood Pressure)
Blood pressure was measured during each administration of ketamine, occurring on days 0, 5, 8, 11, 14, and 21. This vital sign was measured 6 times following the intranasal administration of ketamine: 15 minutes post dose, 30 minutes post dose, 45 minutes post dose, 1 hour post dose, 90 minutes post dose, and 2 hours post dose. Average blood pressure per group was assessed. Medical staff monitoring the ketamine administration were prepared to treat increases in blood pressure greater than 180/110 mm Hg or follow their institutional guidelines if more conservative, if these elevations did not resolve spontaneously within a short time period. Data presented are number of participants with elevated blood pressure at any of the listed time points. (NCT03149991)
Timeframe: Blood pressure was measured during each administration of ketamine, occurring on days 0, 5, 8, 11, 14, and 21. This vital sign was measured 6 times following the intranasal administration of ketamine: 15 minutes post dose, 30 minutes post dose, 45 minutes
| Intervention | Participants (Count of Participants) |
|---|
| Ketamine/Brexpiprazole Arm | 1 |
| Ketamine/Placebo Arm | 0 |
Efficacy on Secondary Outcome Variables
"Montgomery-Asberg Depression Rating Scale (MADRS):This 10-item clinician-rated instrument measures depression severity. Total score range of 0-60 with higher scores indicating more severity.~6-item Hamilton Rating Scale for Depression (HAM-D6): This instrument is completed with a structured interview guide by the clinician based on his/her assessment of the patient's symptoms, with higher scores indicating worse depression. Scores range from 0-22. Experiences were rated based on the past 3 days.~Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scales: These clinician-rated scales rate the severity of the disorder and the global improvement since beginning of the study. Further information is in the baseline measures section." (NCT03149991)
Timeframe: These secondary outcome variables were assessed on Days 0, 1 (except for MADRS this day), 2, 5, 8, 11, 14, 17, 21, 23, 28
| Intervention | score on a scale (Mean) |
|---|
| MADRS, Day 0 | MADRS, Day 2 | MADRS, Day 5 | MADRS, Day 8 | MADRS, Day 11 | MADRS, Day 14 | MADRS, Day 17 | MADRS, Day 21 | MADRS, Day 23 | MADRS, Day 28 | HAMD6, Day 0 | HAMD6, Day 1 | HAMD6, Day 2 | HAMD6, Day 5 | HAMD6, Day 8 | HAMD6, Day 11 | HAMD6, Day 14 | HAMD6, Day 17 | HAMD6, Day 21 | HAMD6, Day 23 | HAMD6, Day 28 | CGI-S, Day 0 | CGI-S, Day 1 | CGI-S, Day 2 | CGI-S, Day 5 | CGI-S, Day 8 | CGI-S, Day 11 | CGI-S, Day 14 | CGI-S, Day 17 | CGI-S, Day 21 | CGI-S, Day 23 | CGI-S, Day 28 | CGI-I, Day 0 | CGI-I, Day 1 | CGI-I, Day 2 | CGI-I, Day 5 | CGI-I, Day 8 | CGI-I, Day 11 | CGI-I, Day 14 | CGI-I, Day 17 | CGI-I, Day 21 | CGI-I, Day 23 | CGI-I, Day 28 |
|---|
| Ketamine/Brexpiprazole Arm | 33.84 | 31.87 | 29.46 | 27.64 | 23.63 | 21.28 | 20.92 | 20.5 | 18.36 | 18.39 | 11 | 10.24 | 10.48 | 10.08 | 9.4 | 7.96 | 7.36 | 6.96 | 6.83 | 6.68 | 6.43 | 4.96 | 4.56 | 4.61 | 4.33 | 4.29 | 3.78 | 3.48 | 3.42 | 3.46 | 3.14 | 3.17 | 4.16 | 3.8 | 3.65 | 3.5 | 3.2 | 2.87 | 2.8 | 2.67 | 2.75 | 2.41 | 2.48 |
,| Ketamine/Placebo Arm | 34.19 | 28.19 | 27.42 | 24.48 | 21.83 | 22.08 | 23.52 | 23.75 | 23.57 | 22.13 | 11.6 | 9.19 | 8.62 | 9.21 | 7.64 | 7.71 | 7.54 | 8.09 | 7.83 | 7.48 | 7.58 | 4.77 | 4.15 | 4.12 | 4 | 3.68 | 3.38 | 3.33 | 3.48 | 3.58 | 3.48 | 3.46 | 4.15 | 3.35 | 3.42 | 3.29 | 2.92 | 2.7 | 2.54 | 2.83 | 2.83 | 2.74 | 2.54 |
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score
The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the participant, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items were rated on a 4-point scale, with a score of 0 (absence of symptoms) to 3 (severe condition) and the global clinical assessment was rated on a 6-point scale, with a score of 0 (absence of symptoms) to 5 (severe akathisia). Total score is the sum of the scores of all 4 items, ranging from 0 to 14, higher scores indicate severe condition. LS mean was determined by ANCOVA model with treatment and study center as main effects and baseline value as covariate. (NCT03198078)
Timeframe: Baseline up to last visit (approximately 6 weeks)
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | 0.01 |
| Aripiprazole | 0.06 |
| Placebo | 0.01 |
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score
The AIMS assessment consists of 12 items rating the involuntary movements: Facial and oral movements (4 items), extremity movements (2 items), and trunk movements (1 item) were observed unobtrusively while the participant is at rest and the investigator also made global judgments on the participant's dyskinesias (2 items), and dental status (2 items). Severity of each item was rated on a 5-point scale, with a score of 0 (absence of symptoms) to 4 (severe condition). Total Score is the sum of the scores of all 12 items, ranging from 0 to 48, higher scores indicate severe condition. LS mean was determined by ANCOVA model with treatment and study center as main effects and baseline value as covariate. (NCT03198078)
Timeframe: Baseline up to last visit (approximately 6 weeks)
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -0.12 |
| Aripiprazole | 0.05 |
| Placebo | -0.06 |
Change From Baseline to Week 6 in Clinical Global Impression Severity (CGI-S) Scale Score
"The CGI-S scale is an investigator-rated evaluation that assesses the severity of a participant's illness on a 7-point scale, ranging from 1 to 7. The investigator answered the question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?. Response choices were: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. Higher scores indicate worse condition. LS mean was determined by the MMRM method with fixed effect of treatment, (pooled) clinical center visit, treatment visit interaction, baseline value, and baseline visit interaction as a covariate, and with an unstructured covariance." (NCT03198078)
Timeframe: Baseline to Week 6
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -0.92 |
| Aripiprazole | -1.01 |
| Placebo | -0.80 |
Mean Change From Baseline in Height
Change in height was reported in centimeters (cm). (NCT03198078)
Timeframe: Baseline up to last visit (approximately 6 weeks)
| Intervention | cm (Mean) |
|---|
| Brexpiprazole | 0.2 |
| Aripiprazole | 0.2 |
| Placebo | 0.3 |
Mean Change From Baseline in Waist Circumference
Change in waist circumference was reported in 'cm'. (NCT03198078)
Timeframe: Baseline up to last visit (approximately 6 weeks)
| Intervention | cm (Mean) |
|---|
| Brexpiprazole | 0.6 |
| Aripiprazole | -0.3 |
| Placebo | 0.0 |
Number of Participants With Treatment-emergent AEs (TEAEs), Serious TEAEs, and TEAEs Graded by Severity
An AE was defined as any untoward medical occurrence in a participant administered with a medicinal product that does not necessarily have a causal relationship with the treatment. An SAE was any AE that results in the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions which is fatal, life-threatening, result in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, and requires inpatient hospitalization or prolongation of existing hospitalization. TEAE is any AE after the start of treatment or if the event was continuous from baseline, medicinal product related, or resulted in death, discontinuation, interruption or reduction of medicinal product. TEAEs were graded on a 3-point scale: 1 (Mild: Discomfort noticed, but no disruption to daily activity), 2 (Moderate: Discomfort sufficient to reduce or affect normal daily activity), and 3 (Severe: Inability to work or perform normal daily activity). (NCT03198078)
Timeframe: From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | Serious TEAEs | Mild TEAEs | Moderate TEAEs | Severe TEAEs |
|---|
| Aripiprazole 10 to 20 mg/Day | 53 | 1 | 47 | 16 | 0 |
,| Brexpiprazole 2 to 4 mg/Day | 44 | 1 | 33 | 17 | 2 |
,| Placebo | 42 | 3 | 32 | 13 | 1 |
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale
The UKU rating scale is a semi-structured interview used to assess the side effects of participants being treated with antipsychotic drugs. The scale is divided into 6 sub-scales: Psychic, neurological, autonomic, other, global assessment by subject, and global assessment by doctor. The scale has a total of 48 items, each item is rated on a 4-point scale (0=not present; 1=mild; 2=moderate; 3=severe), and the total score ranges from 0 to 144. Higher ratings indicate greater impairment. The severe side effects are reported in this outcome measure. (NCT03198078)
Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Psychic: Concentration Difficulties | Psychic: Asthenia/Lassitude | Psychic: Failing Memory | Psychic: Depression | Psychic: Tension/Inner Unrest | Psychic: Increased Duration of Sleep | Psychic: Reduced Duration of Sleep | Psychic: Increased Dream Activity | Psychic: Emotional Indifference | Neurologic: Akathisia | Autonomic: Nausea/Vomiting | Autonomic: Micturition Disturbances | Autonomic: Palpitations/Tachycardia | Autonomic: Increased Tendency to Sweating | Other: Weight Gain | Other: Amenorrhoea | Other: Migraine |
|---|
| Aripiprazole | 10 | 3 | 2 | 2 | 3 | 1 | 1 | 2 | 6 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 |
,| Brexpiprazole | 7 | 6 | 2 | 0 | 4 | 0 | 4 | 0 | 3 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
,| Placebo | 8 | 1 | 4 | 1 | 9 | 0 | 1 | 0 | 6 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 |
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters
Twelve-lead ECG recordings were obtained after the participant was supine and at rest for at least 5 minutes as defined in SAP. (NCT03198078)
Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Rate: Bradycardia | Rhythm: Sinus Bradycardia | Rhythm: Supraventricular Premature Beat | Rhythm: Ventricular Premature Beat | ST/T Morphology: QTcF | ST/T Morphology: QTcN |
|---|
| Aripiprazole | 0 | 0 | 1 | 0 | 1 | 1 |
,| Brexpiprazole | 0 | 0 | 0 | 1 | 0 | 0 |
,| Placebo | 1 | 1 | 1 | 0 | 0 | 0 |
Number of Participants With Potentially Clinically Relevant Laboratory Test Values
Potentially clinically relevant laboratory values assessed included - serum chemistry [including blinded prolactin], hematology, and urinalysis as defined in SAP. (NCT03198078)
Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Alanine Aminotransferase (U/L): High | Bilirubin (mg/dL): High | Cholesterol, Fasting (mg/dL): High | Creatine kinase (U/L): High | Glucose, Fasting (mg/dL): High | HDL Cholesterol, Fasting (mg/dL): Low | LDL Cholesterol, Fasting (mg/dL): High | Triglycerides, Fasting (mg/dL): High | Urate (mg/dL): High | Eosinophils/Leukocytes (%): High | Hematocrit (%): Low | Hemoglobin (g/dL): Low | Leukocytes (10^9/L): Low | Leukocytes (10^9/L): High | Protein, Urine: High |
|---|
| Aripiprazole | 2 | 1 | 3 | 4 | 15 | 10 | 3 | 7 | 0 | 0 | 0 | 0 | 1 | 0 | 2 |
,| Brexpiprazole | 1 | 0 | 2 | 5 | 16 | 12 | 2 | 13 | 0 | 2 | 4 | 2 | 0 | 0 | 2 |
,| Placebo | 0 | 0 | 0 | 1 | 9 | 13 | 0 | 10 | 1 | 0 | 1 | 0 | 0 | 1 | 0 |
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs
Vital sign measurements included body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Blood pressure measurements were made in the supine, sitting, and standing positions after the participant had been in each position for at least 3 minutes as defined in SAP. (NCT03198078)
Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| SBP Sitting (mmHg): Low | SBP Standing (mmHg): Low | SBP Supine (mmHg): Low | DBP Standing (mmHg): Low | DBP Supine (mmHg): Low | Weight (kg): Low | Weight (kg): High | Orthostatic Hypotension (mmHg): Low |
|---|
| Aripiprazole | 0 | 1 | 0 | 0 | 1 | 2 | 5 | 1 |
,| Brexpiprazole | 0 | 1 | 0 | 1 | 0 | 5 | 9 | 2 |
,| Placebo | 1 | 0 | 1 | 0 | 0 | 4 | 5 | 2 |
Number of Participants With Adverse Events (AEs) and Trial Discontinuation Due to AEs
An AE was defined as any untoward medical occurrence in a participant administered with a medicinal product that does not necessarily have a causal relationship with the treatment. (NCT03198078)
Timeframe: From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| AEs | Trial Discontinuation Due to AEs |
|---|
| Aripiprazole | 56 | 1 |
,| Brexpiprazole | 46 | 0 |
,| Placebo | 44 | 2 |
Change From Baseline to Week 6 in PANSS Positive and Negative Sub-Scales Scores
PANSS has 7 positive symptom constructs: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, hostility; and 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. Each item's severity was rated on 7-point scale, with score of 1 (absence of symptoms) to 7 (extremely severe symptoms). PANSS positive & negative subscale scores were the sum of rating scores for 7 positive & 7 negative items respectively. Both scores range from 7 (best possible outcome) to 49 (worst possible outcome). Higher scores denote worsening of symptoms. LS mean was determined by MMRM method with fixed effect of treatment, (pooled) clinical center visit, treatment visit interaction, baseline value, and baseline visit interaction as a covariate, and with an unstructured covariance. (NCT03198078)
Timeframe: Baseline to Week 6
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change From Baseline to Week 6 in PANSS Positive Sub-scale Score | Change From Baseline to Week 6 in PANSS Negative Sub-scale Score |
|---|
| Aripiprazole | -7.29 | -4.77 |
,| Brexpiprazole | -6.58 | -4.70 |
,| Placebo | -5.14 | -3.82 |
Percentage of Participants Achieving Remission
Remission was defined as a score of ≤ 3 on each of the following specific PANSS items: delusions (positive scale item [P] 1), unusual thought content (general scale item [G] 9), hallucinatory behavior (P3), conceptual disorganization (P2), mannerisms/posturing (G5), blunted affect (negative scale item [N] 1), passive/apathetic social withdrawal (N4), and lack of spontaneity and conversation flow (N6). Each item's severity was rated on 7-point scale, with score of 1 (absence of symptoms) to 7 (extremely severe symptoms). Percentage of participants achieving remission was determined by LOCF method. (NCT03198078)
Timeframe: Up to 6 weeks
| Intervention | percentage of participants (Number) |
|---|
| Brexpiprazole | 29.09 |
| Aripiprazole | 35.64 |
| Placebo | 23.30 |
Number of Participants With At Least One Occurrence of Suicidal Behavior or Suicidal Ideation as Recorded on Columbia-Suicide Severity Rating Scale (C-SSRS)
C-SSRS is a scale used to report at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any of the following items: actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior. The suicidal ideation total score is the sum of intensity scores of 5 items (frequency, duration, controllability, deterrents, and reasons for ideation). The score of each intensity item ranges from 0 (none) to 5 (worst) and the total score ranges from 0 to 25. Lower scores indicate improvement. (NCT03198078)
Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Brexpiprazole | 1 |
| Aripiprazole | 2 |
| Placebo | 2 |
Mean Clinical Global Impression Improvement (CGI-I) Scale Score at Week 6
The efficacy of brexpiprazole in the treatment was rated for each participant using the CGI-I. The investigator rated the participant's total improvement whether or not it was entirely due to drug treatment on a 7-point scale, ranging from 0 to 7. Response choices were: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Higher scores indicate worse condition. Mean CGI-I scale score was determined by LOCF method. (NCT03198078)
Timeframe: Week 6
| Intervention | score on a scale (Mean) |
|---|
| Brexpiprazole | 2.86 |
| Aripiprazole | 2.79 |
| Placebo | 3.17 |
Change From Baseline to Week 6 in Children's Global Assessment Scale (CGAS) Total Score
The CGAS is a 100-point rating scale measuring psychological, social, and school functioning for children aged 6-17 years and provides a global measure of the severity of disturbance. The scale is separated into 10-point sections that are headed with a description of the level of functioning and followed by examples matching the interval. The score ranges from 0-100, 1 to 10 indicates the need for constant supervision and 91 to 100 indicates superior functioning in all areas. Higher scores indicate better functioning. LS mean was determined by MMRM method with fixed effect of treatment, (pooled) clinical center visit, treatment visit interaction, baseline value, and baseline visit interaction as a covariate, and with an unstructured covariance. (NCT03198078)
Timeframe: Baseline to Week 6
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | 10.56 |
| Aripiprazole | 12.07 |
| Placebo | 8.08 |
Change From Baseline in Simpson Angus Scale (SAS) Total Score
The SAS consists of a list of 10 symptoms of Parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Severity of each item was rated on a 5-point scale, with a score of 0 (absence of symptoms) to 4 (severe condition). The SAS total score is the sum of the scores of all 10 items, ranging from 0 to 40 where lower scores indicate less severe condition. LS mean was determined by Analysis of Covariance (ANCOVA) model with treatment and study center as main effects and baseline value as covariate. (NCT03198078)
Timeframe: Baseline up to last visit (approximately 6 weeks)
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | 0.04 |
| Aripiprazole | 0.15 |
| Placebo | -0.03 |
Number of Participants With Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT)
The NY-AACENT is used to detect changes in cognitive function subsequent to pharmacological or similar treatments for neurological or psychiatric problems, specifically designed to be used in pediatric population (ages 12 to 17), but could have been utilized with other age groups, as appropriate. Number of participants with at least one occurrence of the corresponding signs/symptoms are reported in this outcome measure. (NCT03198078)
Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Working Memory | Attention/Vigilance | Verbal Learning | Visual Learning | Reasoning | Speed of Processing | Social Cognition | Any Signs/Symptoms |
|---|
| Aripiprazole | 79 | 90 | 70 | 46 | 86 | 84 | 87 | 91 |
,| Brexpiprazole | 88 | 98 | 71 | 46 | 97 | 88 | 91 | 100 |
,| Placebo | 83 | 91 | 69 | 44 | 83 | 82 | 84 | 92 |
Mean Change From Baseline in Weight
Change in weight was reported, in kilograms (kg). (NCT03198078)
Timeframe: Baseline up to last visit (approximately 6 weeks)
| Intervention | kg (Mean) |
|---|
| Brexpiprazole | 0.8 |
| Aripiprazole | 0.5 |
| Placebo | 0.0 |
Percentage of Participants Achieving Response
Response was defined as at least 30% improvement from baseline in PANSS Total Score or CGI score of 1 or 2. The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel, and ranges from 30 (best possible outcome) to 210 (worst possible outcome). The CGI scale is an investigator-rated evaluation that assesses the severity of a participant's illness on a 7-point scale, ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Percentage of participants achieving response was determined by Last Observation Carried Forward (LOCF) method. (NCT03198078)
Timeframe: Up to 6 weeks
| Intervention | percentage of participants (Number) |
|---|
| Brexpiprazole | 43.64 |
| Aripiprazole | 43.56 |
| Placebo | 28.16 |
Mean Change From Baseline in Body Mass Index (BMI)
Change in BMI was reported in kilograms per square meter (kg/m^2). (NCT03198078)
Timeframe: Baseline up to last visit (approximately 6 weeks)
| Intervention | kg/m^2 (Mean) |
|---|
| Brexpiprazole | 0.2 |
| Aripiprazole | 0.3 |
| Placebo | 0.0 |
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) to 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranges from 30 (best possible outcome) to 210 (worst possible outcome). Higher scores indicate worsening of symptoms. Least squares (LS) mean was determined by Mixed-effect model repeated measures (MMRM) method with fixed effect of treatment, (pooled) clinical center visit, treatment visit interaction, baseline value and baseline visit interaction as a covariate, and with an unstructured covariance. (NCT03198078)
Timeframe: Baseline to Week 6
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -22.75 |
| Aripiprazole | -23.95 |
| Placebo | -17.42 |
Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3
The CGI-BP scale refers to the global impression of the participant with respect to bipolar disorder. The scale rates the participant's severity of illness (CGI-BP severity of illness: mania, depression, and overall bipolar illness) based on a 7-point scale: 1 = normal, not at all ill, 2 = minimally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = very severely ill. (NCT03257865)
Timeframe: Baseline, Week 3
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -1.31 |
| Placebo | -1.06 |
Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3
"The YMRS was utilized to assess a participant's level of manic symptoms. It consists of 11 items: 1) elevated mood, 2) increased motor activity-energy, 3) sexual interest, 4) sleep, 5) irritability, 6) speech (rate and amount), 7) language-thought disorder, 8) content, 9) disruptive-aggressive behavior, 10) appearance, and 11) insight. Seven items are rated on a 0- to 4-scale, while four items (Items 5, 6, 8, and 9) are rated on a 0- to 8-scale with 0, 2, 4, 6, and 8 being the possible scores (twice the weight of the other items). For all items, 0 is the best rating and the highest score (4 or 8) is the 'worst' rating. The YMRS total score is the sum of ratings for all 11 items; therefore, possible total scores range from 0 to 60, with higher scores signifying more severe manic symptoms. Comparison between treatment groups was carried out using mixed-effect model repeated measure (MRMM)." (NCT03257865)
Timeframe: Baseline, Week 3
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -12.3 |
| Placebo | -10.7 |
Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3
"The YMRS was utilized to assess a participant's level of manic symptoms. It consists of 11 items: 1) elevated mood, 2) increased motor activity-energy, 3) sexual interest, 4) sleep, 5) irritability, 6) speech (rate and amount), 7) language-thought disorder, 8) content, 9) disruptive-aggressive behavior, 10) appearance, and 11) insight. Seven items are rated on a 0- to 4-scale, while four items (Items 5, 6, 8, and 9) are rated on a 0- to 8-scale with 0, 2, 4, 6, and 8 being the possible scores (twice the weight of the other items). For all items, 0 is the best rating and the highest score (4 or 8) is the 'worst' rating. The YMRS total score is the sum of ratings for all 11 items; therefore, possible total scores range from 0 to 60, with higher scores signifying more severe manic symptoms. Comparison between treatment groups was carried out using mixed-effect model repeated measure (MMRM)." (NCT03259555)
Timeframe: Baseline, Week 3
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Brexpiprazole | -10.6 |
| Placebo | -10.8 |
Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3
The CGI-BP scale refers to the global impression of the participant with respect to bipolar disorder. The scale rates the participant's severity of illness (CGI-BP severity of illness: mania, depression, and overall bipolar illness) based on a 7-point scale: 1 = normal, not at all ill, 2 = minimally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = very severely ill. (NCT03259555)
Timeframe: Baseline, Week 3
| Intervention | units on a scale (Mean) |
|---|
| Brexpiprazole | -1.12 |
| Placebo | -1.21 |
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs severity were graded on a 3-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, and 3 = severe; inability to work or perform normal daily activity. (NCT03287869)
Timeframe: From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
| Intervention | Participants (Count of Participants) |
|---|
| TEAE, Any grade | TEAE, Mild | TEAE, Moderate | TEAE, Severe |
|---|
| Prior Brexpiprazole | 79 | 60 | 31 | 8 |
,| Prior Placebo | 86 | 68 | 29 | 5 |
Sheehan Disability Scale (SDS)
Subjects will complete the SDS at all visits. The change in scores from baseline to study completion will be assessed. The scale itself assesses the level of disability from borderline personality disorder (or target disorder) with higher scores indicating a more debilitating disorder. Scores range from 0-30. (NCT03418675)
Timeframe: Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
| Intervention | score on a scale (Mean) |
|---|
| Visit 1 | Visit 2 | Visit 3 | Visit 4 | Visit 5 | Visit 6 | Visit 7 | Visit 8 |
|---|
| Placebo | 17.3 | 13.3 | 11.5 | 12.4 | 11.7 | 11.2 | 12.0 | 12.7 |
,| Rexulti | 15.8 | 10.7 | 7.8 | 7.8 | 7.0 | 7.9 | 6.9 | 7.7 |
Self Report Version of Zanarini Scale
A self-report scale assessing Borderline Personality severity that will be assessed at all visits.This scale is assessing severity and change in BPD symptoms. This is a 9-item scale measuring severity of different aspects of Borderline Personality Disorder, with each item rated on a 0-4 scale, 0=no symptoms, 4=severe symptoms. Total scores range from 0-36. (NCT03418675)
Timeframe: Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
| Intervention | score on a scale (Mean) |
|---|
| Visit 1 | Visit 2 | Visit 3 | Visit 4 | Visit 5 | Visit 6 | Visit 7 | Visit 8 |
|---|
| Placebo | 18.2 | 12.8 | 10.7 | 10.7 | 9.7 | 9.6 | 8.7 | 9.3 |
,| Rexulti | 17.6 | 10.9 | 7.9 | 8.0 | 7.0 | 6.6 | 6.0 | 5.8 |
Quality of Life Inventory (QOLI)
A self-report assessment of patient perceived quality of life that will be assessed at baseline and visit 8. Higher scores indicate a higher quality of life, whereas lower scores indicate a lower quality of life. Participants are asked to rate the importance of each domain on a 3-point scale ranging from 1=not important to 3=very important, and to rate how satisfied they are with that domain on a 6-point scale, ranging from -3=very dissatisfied to +3=very satisfied. In scoring, importance ratings are multiplied by satisfaction ratings to produce weighted satisfaction scores for each of the 16 domains. Weighted satisfaction scores are summed and divided by the number of domains that were rated as important or very important to produce a raw score, which is then converted to a t-score, which provides a proxy measurement for perceived quality of life. T-scores range from very low perceived quality of life (0-36) to high perceived quality of life (58-77). (NCT03418675)
Timeframe: Baseline (Week 1), Week 12 (Visit 8)
| Intervention | score on a scale (Mean) |
|---|
| Visit 1 | Visit 8 |
|---|
| Placebo | 28.89 | 30.75 |
,| Rexulti | 28.70 | 35.71 |
MINI International Neuropsychiatric Interview
A short-structured interview that assesses comorbid psychiatric disorders according to the DSM 5 criteria. This assessment will be done during the baseline visit. (NCT03418675)
Timeframe: Baseline (Week 1)
| Intervention | Participants (Count of Participants) |
|---|
| Major Depressive Episode (Current) | Major Depressive Episode (Past) | Manic Episode (Current) | Manic Episode (Past) | Hypomanic Episode (Current) | Bipolar I Disorder (Current) | Bipolar I Disorder (Past) | Bipolar II Disorder (Current) | Bipolar II Disorder (Past) | Panic Disorder (Current) | Panic Disorder (Lifetime) | Agoraphobia (Current) | Social Anxiety Disorder (Current) | Obsessive Compulsive Disorder (Current) | Post Traumatic Stress Disorder (Current) | Alcohol Use Disorder (Past 12 months) | Substance Use Disorder (Past 12 months) | Any Psychotic Disorder (Current) | Any Psychotic Disorder (Lifetime) | Major Depressive Disorder with Psychotic Features (Current) | Major Depressive Disorder with Psychotic Features (Past) | Anorexia Nervosa (current) | Bulimia Nervosa (Current) | Binge Eating Disorder (Current) | Generalized Anxiety Disorder (Current) | Antisocial Personality Disorder (Lifetime) | ADHD Combined Type (Current) | ADHD Inattentive Type (Current) | ADHD Hyperactive Type (Current) | Tourette's Syndrome (Lifetime) | Persistent Motor Tic Disorder (Lifetime) | Provisional Vocal Tic Disorder (Lifetime) | Provisional Tic Disorder (Lifetime) | Specific Phobia | Body Dysmorphic Disorder (Current) |
|---|
| Placebo | 16 | 12 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 6 | 11 | 7 | 6 | 3 | 9 | 13 | 11 | 0 | 0 | 0 | 0 | 0 | 4 | 2 | 10 | 8 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 4 | 3 |
,| Rexulti | 18 | 18 | 2 | 3 | 0 | 0 | 0 | 0 | 1 | 6 | 10 | 9 | 9 | 3 | 12 | 8 | 8 | 0 | 1 | 0 | 0 | 1 | 4 | 4 | 15 | 4 | 4 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 2 |
Borderline Evaluation of Severity Over Time (BEST)
A self rated scale used to measure severity and change. The first 12 items of the scale are on a scale from 1-5, with 5 meaning that the item caused extreme distress, severe difficulties in relationships, and/or kept them from getting things done. The lowest rating (1) means it caused little or no problems. Items 13-15 (positive behaviors) are rated according to frequency. Completed at every visit. (NCT03418675)
Timeframe: Assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to week 12) is reported
| Intervention | score on a scale (Mean) |
|---|
| Visit 1 | Visit 8 |
|---|
| Placebo | 40.90 | 29.15 |
,| Rexulti | 40.54 | 23.15 |
Columbia Suicide Severity Rating Scale (CSSRS)
"A self-report scale measuring suicidality. Subjects will complete the scale at all visits. Subjects are asked about suicidal thoughts. If answers are no, rater can proceed to suicidal behavior section where subject is asked about any non-suicidal self injurious behavior. If yes, subject is asked about intensity of ideations. In the event of serious threat to themselves, the subject will be escorted to the emergency room. Total score indicates severity of suicidal ideation and behavior, with lower scores representing lower levels of suicidality and higher scores representing higher levels of suicidality. A score of 0 would reflect no suicidality present, whereas a maximum score of 5 would reflect active suicidal ideation with intent to act." (NCT03418675)
Timeframe: Baseline (Visit 1), Week 12 (Visit 8)
| Intervention | score on a scale (Mean) |
|---|
| Visit 1 | Visit 8 |
|---|
| Placebo | 1.15 | 0.23 |
,| Rexulti | 0.73 | 0.08 |
Hamilton Depression Rating Scale (HAM-D)
A clinician-administered assessment of depression that will be assessed at all study visits (Visits 1-8). Higher total scores indicate higher levels of depression (up to 52), while a score of 0 would indicate no depressive symptoms. (NCT03418675)
Timeframe: Assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to week 12) is reported
| Intervention | change in score on a scale (Mean) |
|---|
| Placebo | -2.09 |
| Rexulti | -3.81 |
Hamilton Anxiety Rating Scale (HAM-A)
A clinician-administered assessment of anxiety that will be assessed at all study visits (Visit 1-Visit 8). Changes in scores from baseline to final visit will be assessed. Higher scores (up to 56) indicate higher levels of anxiety, with 0 being no symptoms of anxiety. (NCT03418675)
Timeframe: assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to Week 12) is reported
| Intervention | change in score on a scale (Mean) |
|---|
| Placebo | -2.41 |
| Rexulti | -4.88 |
Barratt Impulsiveness Scale (BIS)
A self-report assessment of impulsivity that will be assessed at baseline and visit 8. The BIS is composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Items are scored on a 4-point scale: (Rarely/Never = 1, Occasionally = 2, Often = 3, Almost Always/Always = 4). These scores are summed to produce an overall impulsivity score ranging from 30 (not impulsive) to 120 (extremely impulsive). (NCT03418675)
Timeframe: Baseline (Visit 1), Week 12 (Visit 8)
| Intervention | score on a scale (Mean) |
|---|
| Visit 1 | Visit 8 |
|---|
| Placebo | 76.53 | 68.13 |
,| Rexulti | 72.27 | 70.5 |
Zanarini Rating Scale for Borderline Personality Disorder
A clinician-administered scale assessing Borderline Personality Scale severity at all study visits. Scores range from 0-36. Higher scores represent worse Borderline Personality Disorder severity, and lower scores represent milder Borderline Personality Disorder severity. (NCT03418675)
Timeframe: Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
| Intervention | score on a scale (Mean) |
|---|
| Visit 1 | Visit 2 | Visit 3 | Visit 4 | Visit 5 | Visit 6 | Visit 7 | Visit 8 |
|---|
| Placebo | 14.9 | 7.6 | 4.7 | 6 | 4.2 | 5.7 | 5 | 8.4 |
,| Rexulti | 14.9 | 6.7 | 5.3 | 4.4 | 4.5 | 4.9 | 4 | 3.1 |
Symptom Checklist-90 Revised
An instrument that helps evaluate a broad range of psychological problems and symptoms of Borderline Personality Disorder psychopathology. This will be assessed at baseline and visit 8.The 115 items are rated by using a 5-step Likert scale (0=not at all, 4=very strong) and provide a global picture of borderline psychopathology. Global scores of borderline psychopathology are calculated by summing 12 items and range from 0-48. Higher scores indicate more severe symptoms of Borderline Personality Disorder. (NCT03418675)
Timeframe: Baseline, Visit 8 (Week 12)
| Intervention | score on a scale (Mean) |
|---|
| Visit 1 | Visit 8 |
|---|
| Placebo | 26.17 | 20.25 |
,| Rexulti | 25.42 | 14.21 |
Stroop Task
The Stroop task evaluates attention, speed, and accuracy of thinking. Stroop task consists of three separate trials: word, color, and color-word (CW) naming. For each trial, a raw score (correct number of words named) is recorded. The raw score for each trial is converted to a T-score based on participant's age and education level. The possible T-scores range from 15-85 for the word trial, 8-92 for the color trial, and 3-98 for the color-word trial. The interference score (Inter) is also derived from the color-word score, with T-scores ranging from 21-80. Higher numbers indicate better performance. The entered values represent T-scores. (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | T-scores (Mean) |
|---|
| STROOP-CW Baseline | STROOP-CW Week 4 | STROOP-CW Week 8 | STROOP-Inter Baseline | STROOP-Inter Week 4 | STROOP-Inter Week 8 |
|---|
| Brexpiprazole | 48.11 | 41.21 | 50.74 | 49.89 | 43.47 | 51.79 |
High Sensitivity C-Reactive Protein (Hs-CRP)
high sensitivity C-Reactive Protein values will be used to measure inflammation (NCT03427892)
Timeframe: Baseline and at week 8
| Intervention | mg/L (Mean) |
|---|
| hs-CRP Baseline | hs-CRP Week 8 |
|---|
| Brexpiprazole | 3.56 | 3.72 |
Quality of Life in Bipolar Disorder (QOLBD)
"The Quality Of Life in Bipolar Disorder (QOLBD) is a measure of the quality of life in patients with bipolar disorder. All questions on the scale ask about a range of experiences, behaviors, and feeling related to the quality of life. For each question, a participant is asked to indicate how much they agree with each question. The scale consists of 12 questions, with each question measured on a 5-point scale, such as strongly disagree - 1, disagree - 2, neutral - 3, agree - 4, strongly agree - 5. The total possible range of scores on the scale is 12-60. Higher scores indicate better quality of life." (NCT03427892)
Timeframe: Baseline and at week 8
| Intervention | score on a scale (Mean) |
|---|
| QOLBD baseline | QOLBD Week 8 |
|---|
| Brexpiprazole | 30.38 | 40.95 |
Rey Auditoy Verbal Learning Test
Rey Auditory Verbal Learning Test (RAVLT) is a test of verbal learning and declarative memory. During the test, 15 nouns that are read aloud for 5 consecutive trials. Each trial is followed by a free recall test (participant is asked to recall the words that were just read to them). The sum of correctly recalled words across 5 trials is called the total raw score. On completion of Trial 5, an interference list of 15 words (List B) is presented, followed by a free recall test of that list. After a 20-min delay, the examinee is again required to recall the words from list A - this is called the delay raw score. The raw scores on both the total recall and the delay trials (number of words correct across trials 1-5) are converted to standardized T-scores (Mean=50; SD=10; range 20-100) based on participant age and gender. The scores below are presented as T-scores, with higher scores indicative of better performance. (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | T-scores (Mean) |
|---|
| RAVLT T Score Baseline | RAVLT T Score Week 4 | RAVLT T Score Week 8 | RAVLT Delay Baseline | RAVLT Delay Week 4 | RAVLT Delay Week 8 |
|---|
| Brexpiprazole | 37.47 | 37.79 | 40.42 | 39.74 | 37.00 | 39.26 |
Simpson Angus Scale
The Simpson Angus Scale (SAS) measured drug-induced movement side effects. There are 10 items on the scale, with each item scored on a scale of 0-4 (least to most severe). The total possible range of scores across all items is 0-40, with higher scores indicative of worse outcome. (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | score on a scale (Mean) |
|---|
| SAS Baseline | SAS Week 4 | SAS Week 8 |
|---|
| Brexpiprazole | 0.37 | 1.16 | 1.00 |
Systematic Assessment For Treatment Emergent Events
"The Systematic Assessment for Treatment Emergent Effects (SAFTEE) is a self-report scale used in clinical trials and is designed to evaluate the degree to which each possible side effect is bothersome to a participant. There are 55 items on the scale (each item represents a different side effect), with each item rated on a 4-point scale such as not bothersome - 0 (zero), mildly bothersome - 1, moderately bothersome - 2, severely bothersome - 3. The total possible range of scores on the scale is 0-165. The higher scores indicate a higher degree of being bothered by various side effects." (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | score on a scale (Mean) |
|---|
| SAFTEE Baseline | SAFTEE Week 4 | SAFTEE Week 8 |
|---|
| Brexpiprazole | 49.79 | 23.53 | 23.42 |
The Inventory of Depressive Symptomatology Self-Report (IDS-SR30)
An 30 item inventory self report assessing depressive symptoms and mood, within the past seven days. With the score range of 0-90 with higher scores indicating worse outcome. (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | score on a scale (Mean) |
|---|
| IDS-SR30 Baseline | IDS-SR30 Week 4 | IDS-SR30 Week 8 |
|---|
| Brexpiprazole | 41.63 | 18.95 | 17.89 |
The Montgomery-Asberg Depression Rating Scale (MADRS)
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. (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | score on a scale (Mean) |
|---|
| MADRS Baseline | MADRS Week 4 | MADRS Week 8 |
|---|
| Brexpiprazole | 31.95 | 9.95 | 10.95 |
Abnormal Involuntary Movement Scale
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. (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | score on a scale (Mean) |
|---|
| AIMS Baseline | AIMS Week 4 | AIMS Week 8 |
|---|
| Brexpiprazole | 0.63 | 1.26 | 1.16 |
Barnes Akathisia Scale
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).With higher scores reflecting worse outcome. (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | score on a scale (Mean) |
|---|
| BAS Baseline | BAS Week 4 | BAS Week 8 |
|---|
| Brexpiprazole | 0.12 | 2.37 | 2.47 |
Columbia Suicide Severity Rating Scale
The Columbia Suicide Severity Rating Scale (C-SSRS) is a structured interview and rating scale used to measure suicidal thoughts and behaviors. Actual attempts, interrupted attempts, and aborted attempts are measured as positive integers (zero and above). The minimum value for the actual, interrupted, and aborted attempt is zero (reflecting no past suicidal behavior). There is no maximum scale value, as the number of attempts differs for each participant. The entered values represent the average number of actual, interrupted, and aborted attempts in the group. Higher values reflect a higher number of attempts experienced by each participant (equivalent to a worse outcome). (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | attempts (Mean) |
|---|
| C-SSRS Actual Attempts -in lifetime- Baseline | C-SSRS Actual Attempts-since last visit Week 4 | C-SSRS Actual Attempts-since last visit Week 8 | C-SSRS Interrupted Attempts-in lifetime- Baseline | CSSRS Interrupted Attempts-since last visit Week 4 | CSSRS Interrupted Attempts-since last visit Week 8 | C-SSRS Aborted Attempt-in lifetime-Baseline | C-SSRS Aborted Attempt-since last visit-Week 4 | C-SSRS Aborted Attempt-since last visit-Week 8 |
|---|
| Brexpiprazole | 1.35 | 0.00 | 0.00 | 0.10 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
Young Mania Rating Scale (YMRS)
Young Mania Rating Scale is an observer-rated measure of mania symptoms. 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 scoring between anchor points (ranging 1 to 8). Maximum score is 60 and minimum score is 0. (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | score on a scale (Mean) |
|---|
| YMRS Baseline | YMRS Week 4 | YMRS Week 8 |
|---|
| Brexpiprazole | 4.63 | 4.21 | 4.42 |
Trail Making Test (TMT)
The Trail Making Test (TMT) measures attention, speed, and accuracy. TMT consists of two parts: Trails A and Trails B. The performance on each test is measured in seconds and represents how quickly a participant can connect the numbers (Trails A) and the numbers and letters (Trails B) together. The number of seconds it takes to complete each part of TMT is converted to a T-score based on gender, age, race, and education. The T-scores range from 0-100 with higher scores indicating better (faster) performance. The entered data are presented as T-Scores. (NCT03427892)
Timeframe: Baseline through week 8
| Intervention | T-scores (Mean) |
|---|
| TMT A Score Baseline | TMT A Score Week 4 | TMT A Score Week 8 | TMT B Score Baseline | TMT B Score Week 4 | TMT B Score Week 8 |
|---|
| Brexpiprazole | 47.74 | 51.16 | 53.47 | 45.79 | 47.37 | 49.68 |
Phase C: Change From Baseline for Randomization Phase in Sheehan Disability Scale (SDS) Mean Total Score at Week 46
The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0=not at all, to 10=extremely. The SDS total score is the mean of the 3 item responses. The SDS total score ranges from 0 to 10, with higher scores indicating greater functional impairment. Baseline was defined as the last available assessment value between Week 14 and Week 20 in Phase B for this outcome measure. Analysis of covariance (ANCOVA) model was used for analysis. (NCT03538691)
Timeframe: Baseline and Week 46
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase C: Brexpiprazole + ADT | 0.72 |
| Phase C: Placebo + ADT | 0.48 |
Phase C: Percentage of Participants Meeting Any Relapse Criteria
Relapse criteria included: At the same visit, increase in MADRS total score (10 items,7-point scale of 0=no symptoms to 6=severe symptoms, total score of 0 to 60) of 50% from randomization and CGI-S (8-point scale ranging from 0=not assessed to 7=most extremely ill) score ≥4, hospitalization for depression, discontinuation for lack of efficacy/worsening of depression, active suicidality (score of ≥4 on MADRS item 10 of suicidality) or answer of yes on question 4 or 5 of C-SSRS (SI has 5 questions: wish to be dead, non-specific active suicidal thoughts, active SI with any methods [not plan] without intent to act, active SI with some intent to act without specific plan, active SI with specific plan, intent) or answer of yes to any question in suicidal behavior section (5 questions: preparatory acts/behavior, aborted attempt, interrupted attempt, actual attempt [non-fatal], completed suicide). Percentage of participants were rounded off to single decimal point. (NCT03538691)
Timeframe: Up to 26 weeks in Phase C
| Intervention | percentage of participants (Number) |
|---|
| Phase C: Brexpiprazole + ADT | 22.5 |
| Phase C: Placebo + ADT | 20.6 |
Phase C: Time-to-functional Relapse Based on SDS Criteria
Time-to-functional relapse was based on a 30% increase in the SDS mean total score from Phase C Baseline, at least one SDS sub-score at 4 or greater, and an SDS total score ≥7 when all 3 sub-scores were available. The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0=not at all, to 10=extremely. Higher scores of 5 and above are associated with significant functional impairment. (NCT03538691)
Timeframe: Up to 14 days post last dose in Phase C (up to 28 weeks)
| Intervention | days (Median) |
|---|
| Phase C: Brexpiprazole + ADT | 36.0 |
| Phase C: Placebo + ADT | 35.0 |
Phase C: Time-to-Relapse by Any Criteria as Defined in Blinded Addendum
Relapse criteria included:At same visit, increase in Montgomery Asberg Depression Rating Scale[MADRS] total score(10 items, 0=no symptoms to 6=severe symptoms,total score=0 to 60)of 50% from randomization and Clinical Global Impression-Severity of Illness [CGI-](8-point scale of 0=not assessed to 7=most extremely ill)score ≥4,hospitalization for depression, discontinuation for lack of efficacy/worsening of depression, active suicidality(score of ≥4 on MADRS item10 of suicidality)or yes answered on question 4 or 5 of Columbia-Suicide Severity Rating Scale[C-SSRS](Suicidal Ideation [SI] has 5 questions: wish to be dead,non-specific active suicidal thoughts,active SI with any methods [not plan]without intent to act,active SI with some intent to act without specific plan,active SI with specific plan,intent)or yes answered to any question in suicidal behavior section (5 questions:preparatory acts/behavior,aborted attempt,interrupted attempt,actual attempt[non-fatal],completed suicide). (NCT03538691)
Timeframe: Up to 14 days post last dose in Phase C (up to 28 weeks)
| Intervention | days (Median) |
|---|
| Phase C: Brexpiprazole + ADT | 63.0 |
| Phase C: Placebo + ADT | 63.0 |
Phase C: Change From Baseline for Randomization Phase in Each of the SDS Individual Item Scores at Week 46
The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0=not at all, to 10=extremely. Higher scores of 5 and above are associated with significant functional impairment. A positive change from Baseline indicates worsening of symptoms impacting each area. Baseline was defined as the last available assessment value between Week 14 and Week 20 in Phase B for this outcome measure. ANCOVA model was used for analysis. (NCT03538691)
Timeframe: Baseline and Week 46
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Work/School | Social Life | Family Life |
|---|
| Phase C: Brexpiprazole + ADT | 0.46 | 0.91 | 0.78 |
,| Phase C: Placebo + ADT | 0.31 | 0.56 | 0.52 |
Phase C: Change From Baseline for Randomization Phase in MADRS Total Score at Week 46
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants were rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A positive change from Baseline indicates worsening of symptoms. Baseline was defined as the last available assessment value in Phase B for this outcome measure. ANCOVA model was used for analysis. (NCT03538691)
Timeframe: Baseline and Week 46
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase C: Brexpiprazole + ADT | 4.09 |
| Phase C: Placebo + ADT | 4.21 |
Phase C: Percentage of Participants Maintaining Remission
Participants maintaining remission was defined as MADRS total score ≤10. The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants were rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. (NCT03538691)
Timeframe: Weeks 21, 23, 25, 29, 33, 37, 41, 45, and 46
| Intervention | percentage of participants (Number) |
|---|
| Week 21 | Week 23 | Week 25 | Week 29 | Week 33 | Week 37 | Week 41 | Week 45 | Week 46 |
|---|
| Phase C: Brexpiprazole + ADT | 90.34 | 85.22 | 84.79 | 79.89 | 88.55 | 87.92 | 84.78 | 88.14 | 90.91 |
,| Phase C: Placebo + ADT | 91.3 | 82.7 | 82.6 | 85.5 | 88.4 | 89.0 | 89.4 | 89.0 | 91.7 |
Phase C: Change From Baseline for Randomization Phase in CGI-S Score at Week 46
The CGI -S was used to rate the severity of illness for each participant on an 8-point scale ranging from 0 to 7 where 0=not assessed, 1=normal, not at all ill, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill participants. A positive change from Baseline indicates worsening of illness. Baseline was defined as the last available assessment value in Phase B for this outcome measure. ANCOVA model was used for analysis. (NCT03538691)
Timeframe: Baseline and Week 46
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Phase C: Brexpiprazole + ADT | 0.56 |
| Phase C: Placebo + ADT | 0.53 |
Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period
The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. (NCT03548584)
Timeframe: Baseline, Weeks 2, 4, 6, 8, 10, and 12
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change From Baseline at Week 2 | Change From Baseline at Week 4 | Change From Baseline at Week 6 | Change From Baseline at Week 8 | Change From Baseline at Week 10 | Change From Baseline at Week 12 |
|---|
| Brexpiprazole 2 and 3 mg | -5.76 | -12.1 | -16.2 | -19.4 | -22.2 | -22.6 |
,| Placebo | -6.61 | -11.0 | -13.9 | -14.4 | -15.7 | -17.3 |
Change From Baseline to Week 12 in CMAI Subscale Scores
The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. It consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding, as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The four subscales include 12, 6, 4, and 2 items, respectively. The score of the subscale is the sum of the individual items included in the subscale, so the score range for each of the 4 subscales is 0 to 84, 0 to 42, 0 to 28, and 0 to 14, respectively. Higher scores indicate worsening of the condition. A negative change from baseline=improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. (NCT03548584)
Timeframe: Baseline and Week 12
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Aggressive Behavior | Physically Nonaggressive Behavior | Verbally Agitated Behavior | Hiding and Hoarding |
|---|
| Brexpiprazole 2 and 3 mg | -9.09 | -6.45 | -4.39 | -1.50 |
,| Placebo | -7.13 | -5.04 | -3.14 | -1.14 |
Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period
CGI-I is a 7-point scale that requires the clinician to assess whether a participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention. This was rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Higher scores indicate worse condition. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. (NCT03548584)
Timeframe: Baseline, Weeks 2, 4, 6, 8, 10, and 12
| Intervention | score on a scale (Mean) |
|---|
| Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 |
|---|
| Brexpiprazole 2 and 3 mg | 3.70 | 3.19 | 2.92 | 2.80 | 2.62 | 2.66 |
,| Placebo | 3.57 | 3.39 | 3.19 | 3.16 | 2.97 | 2.97 |
CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period
The CMAI assesses frequency of agitated behaviors in elderly persons. The scale consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. Each of the agitated behaviors are scored 1 (never) to 7 (several times an hours), with the total scale score ranging from 29 to 203. Higher score indicates greater frequency of agitated behavior. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. (NCT03548584)
Timeframe: Weeks 2, 4, 6, 8, 10, and 12
| Intervention | percentage of participants (Number) |
|---|
| >/= 20%: Week 2 | >/= 20%: Week 4 | >/= 20%: Week 6 | >/= 20%: Week 8 | >/= 20%: Week 10 | >/= 20%: Week 12 | >/= 30%: Week 2 | >/= 30%: Week 4 | >/= 30%: Week 6 | >/= 30%: Week 8 | >/= 30%: Week 10 | >/= 30%: Week 12 | >/= 40%: Week 2 | >/= 40%: Week 4 | >/= 40%: Week 6 | >/= 40%: Week 8 | >/= 40%: Week 10 | >/= 40%: Week 12 |
|---|
| Brexpiprazole 2 and 3 mg | 11.3 | 29.3 | 43.1 | 59.6 | 65.8 | 68.4 | 3.62 | 10.7 | 22.7 | 32.9 | 38.2 | 42.7 | 1.81 | 4.89 | 10.7 | 16.9 | 20.9 | 23.1 |
,| Placebo | 13.2 | 27.6 | 37.9 | 38.8 | 45.7 | 47.4 | 3.51 | 10.3 | 20.7 | 19.0 | 24.1 | 25.9 | 1.75 | 5.17 | 8.62 | 8.62 | 11.2 | 14.7 |
CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period
The CMAI assesses frequency of agitated behaviors in elderly persons. The scale consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. Each of the agitated behaviors are scored 1 (never) to 7 (several times an hours), with the total scale score ranging from 29 to 203. Higher score indicates greater frequency of agitated behavior. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. (NCT03548584)
Timeframe: Baseline, Weeks 2, 4, 6, 8, 10, and 12
| Intervention | percentage of participants (Number) |
|---|
| Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 |
|---|
| Brexpiprazole 2 and 3 mg | 8.14 | 20.4 | 33.8 | 44.0 | 50.2 | 52.4 |
,| Placebo | 14.0 | 19.0 | 26.7 | 31.0 | 34.5 | 37.1 |
Change From Baseline to Week 12 in the CMAI Total Score
The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. A negative change from baseline indicates improvement. Mixed model repeated measures (MMRM) was used for the analysis. As prespecified in the statistical analysis plan (SAP), data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. (NCT03548584)
Timeframe: Baseline and Week 12
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Brexpiprazole 2 and 3 mg | -22.6 |
| Placebo | -17.3 |
CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period
CGI-I is a 7-point scale that requires the clinician to assess whether a participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention. This was rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Higher scores indicate worse condition. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. (NCT03548584)
Timeframe: Baseline, Weeks 2, 4, 6, 8, 10, and 12
| Intervention | percentage of participants (Number) |
|---|
| Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 |
|---|
| Brexpiprazole 2 and 3 mg | 4.98 | 21.8 | 35.1 | 44.4 | 52.4 | 52.4 |
,| Placebo | 5.26 | 12.1 | 23.3 | 24.1 | 33.6 | 40.5 |
Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period
CGI-S was used to rate the severity of agitation. The score ranges from 0 to 7 with response choices as, 0=not assessed; 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. The higher the value, the more severe the agitation. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. (NCT03548584)
Timeframe: Baseline, Weeks 2, 4, 6, 8, 10, and 12
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Change From Baseline at Week 2 | Change From Baseline at Week 4 | Change From Baseline at Week 6 | Change From Baseline at Week 8 | Change From Baseline at Week 10 | Change From Baseline at Week 12 |
|---|
| Brexpiprazole 2 and 3 mg | -0.21 | -0.53 | -0.74 | -0.97 | -1.14 | -1.20 |
,| Placebo | -0.27 | -0.50 | -0.68 | -0.70 | -0.86 | -0.93 |
Number of Participants With Clinically Significant Differences in Simpson Angus Scale (SAS) Values
SAS scale consists of 10 items including 7 items that address bradykinesia-rigidity and additional single items for tremor, glabellar tap, and salivation. Each item represents a specific physical condition and is rated on a 5-point category rating scale ranging from 0 (complete absence of the condition) to 4 (the condition is present to an extreme degree).The total score is obtained by adding the scores for the 10 individual items making the maximum possible score is 40. Higher scores are indicative of more severe Parkinsonian-type symptoms. (NCT03557931)
Timeframe: Baseline, week 6 and week 12
| Intervention | participants (Number) |
|---|
| Baseline | Week 6 | Week 12 |
|---|
| ASP4345 150 mg | 0 | 0 | 0 |
,| ASP4345 50 mg | 0 | 0 | 0 |
,| Placebo | 0 | 0 | 0 |
Number of Participants With Adverse Event (AE)
Treatment emergent adverse event (TEAE) is defined as an AE observed after starting administration of the study drug and 28 days after the last dose of study drug. A study drug-related TEAE is defined as any TEAE with at least possible relationship to study treatment as assessed by the investigator or with missing assessment of the causal relationship. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, metabolic parameters etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. (NCT03557931)
Timeframe: Baseline up to end of study (EoS) (week 14)
| Intervention | participants (Number) |
|---|
| TEAE | Drug-Related TEAEs | Serious TEAEs | Drug-Related Serious TEAE |
|---|
| ASP4345 150 mg | 28 | 11 | 1 | 0 |
,| ASP4345 50 mg | 28 | 13 | 3 | 0 |
,| Placebo | 45 | 11 | 1 | 0 |
Number of Participants With Clinically Significant Differences in Barnes Akathisia Rating Scale (BARS) Values
BARS is used to rate observable, restless movements of drug induced akathisia and subjective awareness of restlessness and any distress associated with the akathisia. BARS consists of the following 4 items: objective assessment of akathisia symptoms, subjective assessment of the participants's awareness of inner restlessness, distress restlessness, and global clinical assessment of akathisia. First three items are rated on a 4-point scale ranging from 0 (no abnormal movements or absence of inner restlessness or no distress) to 3 (severe akathisia or awareness of intense compulsion to move most of the time or severe distress). The last item, the global clinical assessment of akathisia, is rated on a 6-point scale, ranging from 0 (no evidence of akathisia) to 5 (severe akathisia). Total BARS score ranges from 0 to 14 with a higher score representing worse results. (NCT03557931)
Timeframe: Baseline, week 6 and week 12
| Intervention | participants (Number) |
|---|
| Baseline | Week 6 | Week 12 |
|---|
| ASP4345 150 mg | 0 | 0 | 0 |
,| ASP4345 50 mg | 0 | 0 | 0 |
,| Placebo | 0 | 0 | 0 |
Concentration at Trough Level (Ctrough) for ASP4345
Ctrough concentration for ASP4345 was reported. (NCT03557931)
Timeframe: Predose: day 7, day 14, day 21, day 42 and day 84/EoT
| Intervention | nanogram per milliliter (ng/mL) (Mean) |
|---|
| Day 7 Pre-dose | Day 14 Pre-dose | Day 21 Pre-dose | Day 42 Pre-dose | Day 84 Pre-dose |
|---|
| ASP4345 150 mg | 483.84 | 428.88 | 384.48 | 471.78 | 433.56 |
,| ASP4345 50 mg | 175.041 | 182.903 | 172.040 | 207.145 | 204.914 |
Number of Participants With Clinically Significant Differences in Columbia-Suicide Severity Rating Scale (C-SSRS) Values
The C-SSRS is a questionnaire used for suicide risk assessment. Affirmative or negative responses are provided to items 1 to 5 for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods [not plan] without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and items 6 to 10 for suicide behavior (6. Preparatory acts or behavior, 7. Aborted attempt, 8. Interrupted attempt, 9. Actual attempt, 10. Completed suicide). (NCT03557931)
Timeframe: Baseline up to EoS (week 14)
| Intervention | participants (Number) |
|---|
| Placebo | 0 |
| ASP4345 50 mg | 0 |
| ASP4345 150 mg | 0 |
Change From Baseline to Week 12/End of Treatment (EoT) in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score
The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (i.e., working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). The MCCB neurocognitive composite score is a standardized mean of the six domain scores (excluding social cognition). Raw scores are converted to age and sex adjusted t-scores which are standardized to normative data, and have a mean of 50 and standard deviation of 10 in the general healthy population. A higher score indicates less impairment. (NCT03557931)
Timeframe: Baseline and week 12/end of treatment (EoT)
| Intervention | T-score (Least Squares Mean) |
|---|
| Placebo | 1.15 |
| ASP4345 50 mg | 1.34 |
| ASP4345 150 mg | 0.87 |
Number of Participants With Clinically Significant Differences in Abnormal Involuntary Movement Scale (AIMS) Values
AIMS is a 14-item scale. Items 1 to 8 are rated on a 5-point scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Item 9 assesses the participant's incapacitation due to abnormal movements, and item 10 assesses the participant's awareness of the abnormal movements and associated distress. Items 9 and 10 are rated on 5-point scales ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Items 11 to 14 are yes/no questions regarding the global judgement and dental status of the participant. The total score is the sum of the scores for the 14 items and the possible total score ranges from 0 to 44. A higher total score is indicative of more severe dyskinetic movements. (NCT03557931)
Timeframe: Baseline, week 6 and week 12
| Intervention | participants (Number) |
|---|
| Baseline | Week 6 | Week 12 |
|---|
| ASP4345 150 mg | 0 | 0 | 0 |
,| ASP4345 50 mg | 0 | 0 | 0 |
,| Placebo | 0 | 0 | 0 |
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity
"An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs with an onset date on or after the first dose of brexpiprazole. They are all adverse events that started after start of brexpiprazole; or if the event was continuous from baseline and was worsening, serious, study drug-related, or resulted in death, discontinuation, interruption, or reduction of study therapy.~Adverse events were graded on a 3-point scale. The intensity of an adverse experience was defined as follows: 1 = Mild: Discomfort noticed, but no disruption to daily activity, 2 = Moderate: Discomfort sufficient to reduce or affect normal daily activity, and 3 = Severe: Inability to work or perform normal daily activity." (NCT03594123)
Timeframe: From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
| Intervention | percentage of participants (Number) |
|---|
| Mild | Moderate | Severe |
|---|
| Prior Brexpiprazole | 20.9 | 9.2 | 3.1 |
,| Prior Placebo | 13.5 | 19.8 | 0 |
Maximum (Peak) Plasma Concentration (Cmax) of Brexpiprazole
(NCT03902574)
Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12,16, 24, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours postdose
| Intervention | ng/mL (Mean) |
|---|
| Conventional Tablet | 23.31 |
| ODT Without Water | 24.24 |
| ODT With Water | 23.75 |
Area Under the Concentration-time Curve Calculated to the Last Observable Concentration at Time t (AUCt) of Brexpiprazole
(NCT03902574)
Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12,16, 24, 48, 72, 96, 120, 144, 168, 216, 264, and 312 hours postdose
| Intervention | ng*h/mL (Mean) |
|---|
| Conventional Tablet | 1250 |
| ODT Without Water | 1340 |
| ODT With Water | 1260 |