Trial Outcomes & Findings for Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy (NCT NCT01942785)

NCT ID: NCT01942785

Last Updated: 2016-03-15

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 55 participants
• Primary outcome timeframe: Baseline and Week 6
• Results posted on: 2016-03-15

Participant Flow

Of the 55 patients enrolled, only 54 were exposed to IMP and therefore included in the all-patients-treated set (APTS)

Participant milestones

Measure	Brexpiprazole Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Overall Study STARTED	54
Overall Study COMPLETED	50
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	Brexpiprazole Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Overall Study Adverse Event	2
Overall Study Withdrawal by Subject	1
Overall Study Protocol Violation	1

Baseline Characteristics

Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy

Baseline characteristics by cohort

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Age, Continuous	42.41 years STANDARD_DEVIATION 10.31 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
MADRS total score	28.52 units on a scale STANDARD_DEVIATION 4.51 • n=5 Participants
CGI-S score	4.09 units on a scale STANDARD_DEVIATION 0.40 • n=5 Participants
IDS-C30 item 6 score	2.20 units on a scale STANDARD_DEVIATION 0.41 • n=5 Participants
BIS-11 total score	73.20 units on a scale STANDARD_DEVIATION 12.82 • n=5 Participants
KSQ anger-hostility score	14.83 units on a scale STANDARD_DEVIATION 4.78 • n=5 Participants
AAQ anger attacks no	37 participants n=5 Participants
AAQ anger attacks yes	17 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in SIS Total Score	-21.13 units on a scale Standard Error 2.55

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in SIS Item 1 Score	-3.45 units on a scale Standard Error 0.36

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in IDS-C30 Item 6 Score	-1.22 units on a scale Standard Error 0.13

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in Delay Discounting - Log-transformed MCQ Scores	0.00 log-transformed units on a scale Standard Error 0.24

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in BIS-11 Total Score	-4.85 units on a scale Standard Error 0.86

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in KSQ Anger-hostility Subscore	-7.72 units on a scale Standard Error 0.92

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS) and OC. Only patients who have both baseline and Week 6 data observed were included; the number of participants analysed is therefore smaller than the defined FAS.

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.

Outcome measures

Measure	Brexpiprazole n=50 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Shift From Baseline to Week 6 in Anger Attacks (AAQ) no to no	28 participants
Shift From Baseline to Week 6 in Anger Attacks (AAQ) no to yes	5 participants
Shift From Baseline to Week 6 in Anger Attacks (AAQ) yes to no	15 participants
Shift From Baseline to Week 6 in Anger Attacks (AAQ) yes to yes	2 participants

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in IDS-C30 Total Score	-17.81 units on a scale Standard Error 1.57

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in KSQ Depression Subscore	-7.70 units on a scale Standard Error 0.93

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in MADRS Total Score	-14.19 units on a scale Standard Error 1.27

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in CPFQ Total Score	-7.72 units on a scale Standard Error 0.97

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in CGI-S Score	-1.43 units on a scale Standard Error 0.16

PRIMARY outcome

Timeframe: Week 6

Population: Full-analysis set (FAS), this endpoint presents descriptive statistics for CGI-I based on patients who have CGI-I score observed at Week 6; the number of participants analysed is therefore smaller than the defined FAS.

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.

Outcome measures

Measure	Brexpiprazole n=50 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
CGI-I Score at Week 6	2.18 units on a scale Standard Error 0.16

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Full-analysis set (FAS)

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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in KSQ Total Score	-24.36 units on a scale Standard Error 2.94

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: full-analysis set (FAS). Only patients who have observed data at Week 6 were included in the ANCOVA analysis; the number of participants analysed is therefore smaller than the defined FAS.

DPDT consists of approximately 110 choices between an immediate reward or a higher delayed reward, and between an immediate reward or a higher reward that only comes with a certain probability. The tasks are scored independently of each other and do not yield a total score. There will be two derived variables from this task; a delayed discounting rate and a probability discounting rate. The delay discounting value takes values from 0 and up, a higher delay discounting value indicates greater impulsivity. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Outcome measures

Measure	Brexpiprazole n=47 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in Delay Discounting - Log-transformed EDT DPDT Scores DPDT delay score	-0.223 log transformed units on a scale Standard Error 0.349
Change From Baseline to Week 6 in Delay Discounting - Log-transformed EDT DPDT Scores DPDT Probability Score	-0.295 log transformed units on a scale Standard Error 0.271

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: full-analysis set (FAS). Only patients who have observed data at Week 6 were included in the ANCOVA analysis; the number of participants analysed is therefore smaller than the defined FAS.

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.

Outcome measures

Measure	Brexpiprazole n=47 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in Delay Discounting - EDT DRT Score	0.74 units on a scale Standard Error 1.97

PRIMARY outcome

Timeframe: Week 6 and Week 10

Population: Completer's-analysis set (CAS)

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.

Outcome measures

Measure	Brexpiprazole n=48 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Week 6 to Week 10 in SIS Total Score	4.4 units on a scale Standard Error 2.4

PRIMARY outcome

Timeframe: Week 6 and Week 10

Population: Completer's-analysis set (CAS). Only patients who have observed data at Week 10 were included in the ANCOVA analysis; the number of participants analysed is therefore smaller than the defined CAS.

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.

Outcome measures

Measure	Brexpiprazole n=47 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Week 6 to Week 10 in SIS Item 1 Score	0.5 units on a scale Standard Error 0.4

PRIMARY outcome

Timeframe: Week 6 and Week 10

Population: Completer's-analysis set (CAS). Only patients who have observed data at Week 10 were included in the ANCOVA analysis; the number of participants analysed is therefore smaller than the defined CAS.

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.

Outcome measures

Measure	Brexpiprazole n=47 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Week 6 to Week 10 in Delay Discounting - MCQ Scores	0.35 log-transformed units on a scale Standard Error 0.15

PRIMARY outcome

Timeframe: Week 6 and Week 10

Population: Completer's-analysis set (CAS). Only patients who have observed data at Week 10 were included in the ANCOVA analysis.

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.

Outcome measures

Measure	Brexpiprazole n=47 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Week 6 to Week 10 in BIS-11 Total Score	-1.2 units on a scale Standard Error 0.9

PRIMARY outcome

Timeframe: Week 6 and Week 10

Population: Completer's-analysis set (CAS)

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.

Outcome measures

Measure	Brexpiprazole n=48 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Week 6 to Week 10 in KSQ Anger-hostility Subscore	1.2 units on a scale Standard Error 1.0

PRIMARY outcome

Timeframe: Week 6 and Week 10

Population: Completer's-analysis set (CAS)

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.

Outcome measures

Measure	Brexpiprazole n=48 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Week 6 to Week 10 in KSQ Depression Subscore	2.1 units on a scale Standard Error 1.0

PRIMARY outcome

Timeframe: Week 6 and Week 10

Population: Completer's-analysis set (CAS)

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.

Outcome measures

Measure	Brexpiprazole n=48 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Week 6 to Week 10 in CGI-S Score	0.3 units on a scale Standard Error 0.1

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: full-analysis set (FAS)

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 <median at baseline. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in MADRS Total Score in Patients With a Pre-defined Baseline BIS-11 Total Score BIS-11_HIGH (n=27)	-14.41 units on a scale Standard Error 1.71
Change From Baseline to Week 6 in MADRS Total Score in Patients With a Pre-defined Baseline BIS-11 Total Score BIS-11_LOW (n=27)	-15.45 units on a scale Standard Error 1.78

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: full-analysis set (FAS)

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 <median at baseline. 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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
Change From Baseline to Week 6 in CGI-S Score in Patients With a Pre-defined Baseline BIS-11 Total Score BIS-11_HIGH (n=27)	-1.31 units on a scale Standard Error 0.21
Change From Baseline to Week 6 in CGI-S Score in Patients With a Pre-defined Baseline BIS-11 Total Score BIS-11_LOW (n=27)	-1.53 units on a scale Standard Error 0.20

PRIMARY outcome

Timeframe: Week 6

Population: full-analysis set (FAS)

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 <median at baseline. 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.

Outcome measures

Measure	Brexpiprazole n=54 Participants Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily, tablets, for oral use
CGI-I Score at Week 6 Patients With a Pre-defined Baseline BIS-11 Total Score BIS-11_HIGH (n=27)	2.48 units on a scale Standard Error 0.23
CGI-I Score at Week 6 Patients With a Pre-defined Baseline BIS-11 Total Score BIS-11_LOW (n=23)	1.83 units on a scale Standard Error 0.20

Adverse Events

Brexpiprazole

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Brexpiprazole n=54 participants at risk Brexpiprazole adjunct to open-label commercially available Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin Norepinephrine Reuptake Inhibitor (SNRI) antidepressant treatment (ADT) Brexpiprazole: 2-3 mg/day, once daily dose, tablets, for oral use
Gastrointestinal disorders Diarrhoea	5.6% 3/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events
Gastrointestinal disorders Dry mouth	7.4% 4/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events
General disorders Fatigue	7.4% 4/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events
Injury, poisoning and procedural complications Fall	5.6% 3/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events
Investigations Weight increased	5.6% 3/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events
Metabolism and nutrition disorders Increased appetite	7.4% 4/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events
Nervous system disorders Akathisia	20.4% 11/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events
Nervous system disorders Dizziness	5.6% 3/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events
Nervous system disorders Headache	11.1% 6/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events
Nervous system disorders Somnolence	5.6% 3/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events
Psychiatric disorders Insomnia	7.4% 4/54 • Baseline to end of treatment (week 6) Treatment-Emergent Adverse Events

Additional Information

Study director

Email contact via H. Lundbeck A/S

Email: LundbeckClinicalTrials@lundbeck.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place