Trial Outcomes & Findings for Study of Brexpiprazole as Adjunctive Treatment of Sleep Disturbances in Patients With Major Depressive Disorder (NCT NCT01942733)

NCT ID: NCT01942733

Last Updated: 2019-03-20

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 44 participants
• Primary outcome timeframe: Baseline and Week 8
• Results posted on: 2019-03-20

Participant Flow

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	44
Overall Study COMPLETED	41
Overall Study NOT COMPLETED	3

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 Lost to Follow-up	1
Overall Study Non-compliance with IMP	1
Overall Study Administrative	1

Baseline Characteristics

Study of Brexpiprazole as Adjunctive Treatment of Sleep Disturbances in Patients With Major Depressive Disorder

Baseline characteristics by cohort

Measure	Brexpiprazole n=44 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	44.4 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
MADRS total score	28.3 units on a scale STANDARD_DEVIATION 3.8 • n=5 Participants
CGI-S score	4.3 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants
ESS total score	9.1 units on a scale STANDARD_DEVIATION 4.7 • n=5 Participants
ISI total score	19.4 units on a scale STANDARD_DEVIATION 3.9 • n=5 Participants
CPFQ total score	27.1 units on a scale STANDARD_DEVIATION 5.3 • n=5 Participants
BRIAN total score	51.7 units on a scale STANDARD_DEVIATION 10.3 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=44 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
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Parameters PSG LPS (n=40)	-24.9 minutes (min) Standard Error 4.8
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Parameters PSG SOL (n=40)	-19.7 minutes (min) Standard Error 3.8
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Parameters PSG WASO (n=40)	-26.4 minutes (min) Standard Error 6.1
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Parameters PSG TST (n=41)	49.0 minutes (min) Standard Error 8.2

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=40 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
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Number of Awakenings (PSG NAW)	0.06 number of events Standard Error 0.8

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=41 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
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Sleep Efficiency (PSG SE)	10.4 percentage (%) Standard Error 1.7

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=21 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
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Sleep Efficiency (SE)	13.4 percentage of time Standard Error 3.2

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=44 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
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) CSD-M TST (n=21)	69.9 minutes (min) Standard Error 14.6
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) CSD-M SOL (n=21)	-37.1 minutes (min) Standard Error 12.3
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) CSD-M WASO (n=21)	-42.9 minutes (min) Standard Error 29.0

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=21 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
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Number of Awakenings (NAW)	0.0 number Standard Error 0.5

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=44 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
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography Stage N1 (n=40)	-0.7 percentage of total sleep duration Standard Error 0.7
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography Stage N2 (n=40)	3.5 percentage of total sleep duration Standard Error 1.5
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography Stage N3 (n=40)	-2.2 percentage of total sleep duration Standard Error 0.8
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography Stage REM (n=40)	-0.6 percentage of total sleep duration Standard Error 1.1

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=44 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
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography (Continued) Stage N1 Duration (n=41)	4.5 minutes Standard Error 2.5
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography (Continued) Stage N2 Duration (n=41)	43.1 minutes Standard Error 8.3
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography (Continued) Stage N3 Duration (n=41)	-3.1 minutes Standard Error 3.0
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography (Continued) Stage REM Duration (n=41)	4.5 minutes Standard Error 4.4
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography (Continued) Latency to REM Sleep Duration (n=38)	-16.2 minutes Standard Error 14.4

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=41 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 8 in ISI Total Score	-9.2 units on a scale Standard Error 1.1

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=41 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 8 on ESS Total Score	-2.6 units on a scale Standard Error 0.7

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=40 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
Changes From Baseline to Week 8 in Response Speed as Assessed Using a PVT Device	-0.2 speed (per second) Standard Error 0.1

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=40 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
Changes From Baseline to Week 8 in Number of Lapses as Assessed Using a PVT Device	2.1 number Standard Error 2.4

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=33 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 8 on BL-VAS-s (Evening) Score	1.4 units on a scale Standard Error 4.2

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=34 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 8 on BL-VAS-s (Morning) Score	-9.2 units on a scale Standard Error 4.5

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=23 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 8 on BL-VAS-s Scores (Noon)	-7.4 units on a scale Standard Error 6.7

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=41 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 8 in CPFQ Total Score	-8.4 units on a scale Standard Error 1.1

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=9 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
Changes From Baseline to Week 8 in Circadian and Biological Rhythm Time to peak cortisol concentration	-60 minutes Standard Error 23
Changes From Baseline to Week 8 in Circadian and Biological Rhythm Time to DLMO	48 minutes Standard Error 49
Changes From Baseline to Week 8 in Circadian and Biological Rhythm Phase angle	108 minutes Standard Error 61

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=41 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 8 in MADRS Total Score	-16.0 units on a scale Standard Error 1.7

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=41 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 8 in CGI-S Score	-1.8 units on a scale Standard Error 0.2

PRIMARY outcome

Timeframe: Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=41 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
Percentage of MADRS Responders at Week 8	56 percentage of patients

PRIMARY outcome

Timeframe: Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=41 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
Percentage of MADRS Remitters at Week 8	54 percentage of patients

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=44 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
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Actigraphy (ACT) Parameters ACT TST (n=33)	-9.0 minutes Standard Error 15.7
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Actigraphy (ACT) Parameters ACT WASO (n=33)	-6.1 minutes Standard Error 6.5
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Actigraphy (ACT) Parameters ACT SOL (n=32)	-5.5 minutes Standard Error 3.6

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=33 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
Changes From Baseline to Week 8 on Sleep Efficiency (SE) as Assessed by Actigraphy (ACT)	-1.3 percentage of time Standard Error 3.7

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=33 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
Changes From Baseline to Week 8 on Number of Awakenings (NAW) as Assessed by Actigraphy (ACT)	-2.0 number of events Standard Error 1.1

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=41 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 8 in BRIAN Total Score	-17.4 units on a scale Standard Error 1.9

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full-analysis set (FAS) comprised all patients treated, who had a valid baseline assessment and at least one valid post-baseline efficacy assessment. The analysis was performed using observed cases (OC) data.

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.

Outcome measures

Measure	Brexpiprazole n=41 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 8	2.2 units on a scale Standard Error 1.1

Adverse Events

Brexpiprazole

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Brexpiprazole n=44 participants at risk The all-patients-treated set (APTS) comprises all patients who took at least one dose of brexpiprazole.
Gastrointestinal disorders Nausea	13.6% 6/44 • Baseline to end of treatment (Week 8)
General disorders Fatigue	6.8% 3/44 • Baseline to end of treatment (Week 8)
Infections and infestations Upper respiratory tract infection	9.1% 4/44 • Baseline to end of treatment (Week 8)
Investigations Weight increased	9.1% 4/44 • Baseline to end of treatment (Week 8)
Nervous system disorders Headache	11.4% 5/44 • Baseline to end of treatment (Week 8)
Nervous system disorders Sedation	13.6% 6/44 • Baseline to end of treatment (Week 8)
Nervous system disorders Somnolence	9.1% 4/44 • Baseline to end of treatment (Week 8)

Additional Information

Study director

Email contact via H. Ludbeck A/S

Email: LundbeckClinicalTrials@lundbeck.com

Results disclosure agreements

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