Sleep DisturbancesPhase 3NCT01942733

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

A Phase 3 study testing Brexpiprazole in people with Sleep Disturbances, run by H. Lundbeck A/S.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

To assess effects of brexpiprazole on sleep patterns of depressed patients with sleep disturbances. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Sleep Disturbances
What is being tested?: Brexpiprazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 44 participants
Where: No sites listed yet
Study dates: Sep 2013to Aug 2014
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

The patient has a Major Depressive Episode (MDE) associated to Major Depressive Disorder (MDD), diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR™). The current MDE should be confirmed using the Mini International Neuropsychiatric Interview (MINI).
The patient has an inadequate response to at least one antidepressant treatment (including the treatment the patient is taking at screening) in the current MDE, as documented by self-report as less than a pre-defined response on the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ).
The patient has a pre-defined Montgomery Aasberg Depression Rating Scale (MADRS) total score, and a pre-defined Clinical Global Impression - Severity of Illness (CGI-S) score at screening, and has had the current MDE for ≥10 weeks.
The patient is currently treated for the current MDE with an adequate selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant treatment for ≥6 weeks, at the same dosage for ≥2 weeks.
The patient has sleep disturbances (difficulty falling asleep and/or difficulty staying asleep and/or problem waking up too early) confirmed by a pre-defined Insomnia Severity Index (ISI) score.
The patient agrees to protocol-defined use of effective contraception.

Show all 14Show fewer

Entry Criteria to Treatment Period (Baseline Visit):
The patient still fulfils DSM-IV-TR™ criteria for MDE.
The patient received the same SSRI or SNRI antidepressant treatment at adequate dose during the entire lead-in period.
The patient has a pre-defined MADRS total score.
The patient's improvement in the MADRS total score is a pre-defined percentage compared to screening.
The patient has a pre-defined Clinical Global Impression - Global Improvement (CGI-I) score.
The patient has sleep disturbances (difficulty falling asleep and/or difficulty staying asleep and/or problem waking up too early) confirmed by a pre-defined ISI score.
The patient has sleep disturbances confirmed by pre-defined Latency to Persistent Sleep (LPS) and pre-defined Sleep Efficiency (SE).

Who cannot join

The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.
Other inclusion and exclusion criteria may apply.

About this study

Official title: Interventional, Open-label, Flexible-dose, Exploratory Study of Brexpiprazole as Adjunctive Treatment of Sleep Disturbances in Patients With Major Depressive Disorder

To assess effects of brexpiprazole on sleep patterns of depressed patients with sleep disturbances.

Conditions: Sleep Disturbances
Being tested: Brexpiprazole
Medical subject headings: Parasomnias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BrexpiprazoleDrug
2-3 mg/day, once daily, tablets, for oral use. The patients received 1mg/day brexpiprazole during Week 1 and 2mg/day during Week 2 (up-titration) and from Weeks 3 to 6 they received 3mg/day; depending on tolerability the dose could be reduced to 2mg/day based on the investigator's judgment.

Study groups in NCT01942733
Study group	Role	What they receive
Brexpiprazole	Experimental	Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT) Receives: Drug: Brexpiprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Week 8
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.
Measured: Week 8
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.
Measured: Baseline and Week 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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8
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.
Measured: Baseline and Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2013Aug 2014

First posted16 Sep 2013 (estimated)
Study startSep 2013
Primary completionAug 2014
Study completionAug 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Sleep DisturbancesStudies of the same condition, open and under way.
More trials run by H. Lundbeck A/SThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01942733
Sponsor's protocol ID: 15352A
Status last verified: Mar 2019
First submitted: 11 Sep 2013
Last updated: 20 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Krystal AD, Mittoux A, Lindsten A, Baker RA. Chronobiologic parameter changes in patients with major depressive disorder and sleep disturbance treated with adjunctive brexpiprazole: An open-label, flexible-dose, exploratory substudy. J Affect Disord. 2021 Jan 1;278:288-295. doi: 10.1016/j.jad.2020.09.026. Epub 2020 Sep 11.
PubMed 32979560
Krystal AD, Mittoux A, Meisels P, Baker RA. Effects of Adjunctive Brexpiprazole on Sleep Disturbances in Patients With Major Depressive Disorder: An Open-Label, Flexible-Dose, Exploratory Study. Prim Care Companion CNS Disord. 2016 Sep 8;18(5). doi: 10.4088/PCC.15m01914.
PubMed 27835722

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Sleep Disturbances trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Interventional, Open-label, Flexible-dose, Exploratory Study of Brexpiprazole as Adjunctive Treatment of Sleep Disturbances in Patients With Major Depressive Disorder
ClinicalTrials.gov ID: NCT01942733
Acronym / sponsor ID: 15352A
Conditions: Sleep Disturbances
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 44 participants (actual)
Lead sponsor: H. Lundbeck A/SIndustry (pharma, biotech, devices)
Study start: Sep 2013
Primary completion: Aug 2014 (actual)
Study completion: Aug 2014 (actual)
First posted: 16 Sep 2013 (estimated)
Results: Posted 1 Mar 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To assess effects of brexpiprazole on sleep patterns of depressed patients with sleep disturbances.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Brexpiprazole	Experimental	Drug: BrexpiprazoleBrexpiprazole adjunct to open-label treatment with a commercially available antidepressant treatment (ADT)

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

The patient has a Major Depressive Episode (MDE) associated to Major Depressive Disorder (MDD), diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR™). The current MDE should be confirmed using the Mini International Neuropsychiatric Interview (MINI).
The patient has an inadequate response to at least one antidepressant treatment (including the treatment the patient is taking at screening) in the current MDE, as documented by self-report as less than a pre-defined response on the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ).
The patient has a pre-defined Montgomery Aasberg Depression Rating Scale (MADRS) total score, and a pre-defined Clinical Global Impression - Severity of Illness (CGI-S) score at screening, and has had the current MDE for ≥10 weeks.
The patient is currently treated for the current MDE with an adequate selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant treatment for ≥6 weeks, at the same dosage for ≥2 weeks.
The patient has sleep disturbances (difficulty falling asleep and/or difficulty staying asleep and/or problem waking up too early) confirmed by a pre-defined Insomnia Severity Index (ISI) score.

Key exclusion criteria (2 listed)

The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.
Other inclusion and exclusion criteria may apply.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Brexpiprazole2-3 mg/day, once daily, tablets, for oral use. The patients received 1mg/day brexpiprazole during Week 1 and 2mg/day during Week 2 (up-titration) and from Weeks 3 to 6 they received 3mg/day; depending on tolerability the dose could be reduced to 2mg/day based on the investigator's judgment.	Drug	Brexpiprazole

Primary outcome

Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Parameters
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Number of Awakenings (PSG NAW)
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Sleep Efficiency (PSG SE)
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Sleep Efficiency (SE)
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M)
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Number of Awakenings (NAW)
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography (Continued)
Time frame: Baseline and Week 8
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.
Change From Baseline to Week 8 in ISI Total Score
Time frame: Baseline and Week 8
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.
Change From Baseline to Week 8 on ESS Total Score
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 in Response Speed as Assessed Using a PVT Device
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 in Number of Lapses as Assessed Using a PVT Device
Time frame: Baseline and Week 8
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.
Change From Baseline to Week 8 on BL-VAS-s (Evening) Score
Time frame: Baseline and Week 8
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.
Change From Baseline to Week 8 on BL-VAS-s (Morning) Score
Time frame: Baseline and Week 8
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.
Change From Baseline to Week 8 on BL-VAS-s Scores (Noon)
Time frame: Baseline and Week 8
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.
Change From Baseline to Week 8 in CPFQ Total Score
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 in Circadian and Biological Rhythm
Time frame: Baseline and Week 8
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.
Change From Baseline to Week 8 in MADRS Total Score
Time frame: Baseline and 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. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.
Change From Baseline to Week 8 in CGI-S Score
Time frame: Baseline and Week 8
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.
Percentage of MADRS Responders at Week 8
Time frame: 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.
Percentage of MADRS Remitters at Week 8
Time frame: 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.
Changes From Baseline to Week 8 on Sleep Quality as Assessed by Actigraphy (ACT) Parameters
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 on Sleep Efficiency (SE) as Assessed by Actigraphy (ACT)
Time frame: Baseline and Week 8
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.
Changes From Baseline to Week 8 on Number of Awakenings (NAW) as Assessed by Actigraphy (ACT)
Time frame: Baseline and Week 8
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.
Change From Baseline to Week 8 in BRIAN Total Score
Time frame: Baseline and Week 8
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.
CGI-I Score at Week 8
Time frame: Baseline and 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.

Results and safety

Results posted to the registry on 1 Mar 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Brexpiprazole	44	41

Primary outcome: Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Parameters

Time frame: Baseline and Week 8. Mean (Standard Error). Unit: minutes (min)

Measure	Brexpiprazole n = 44
PSG LPS (n=40)	-24.9 (4.8)
PSG SOL (n=40)	-19.7 (3.8)
PSG WASO (n=40)	-26.4 (6.1)
PSG TST (n=41)	49.0 (8.2)

Population analysed: 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.

Primary outcome: Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Number of Awakenings (PSG NAW)

Time frame: Baseline and Week 8. Mean (Standard Error). Unit: number of events

Measure	Brexpiprazole n = 40
Value	0.06 (0.8)

Primary outcome: Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Sleep Efficiency (PSG SE)

Time frame: Baseline and Week 8. Mean (Standard Error). Unit: percentage (%)

Measure	Brexpiprazole n = 41
Value	10.4 (1.7)

Primary outcome: Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Sleep Efficiency (SE)

Time frame: Baseline and Week 8. Mean (Standard Error). Unit: percentage of time

Measure	Brexpiprazole n = 21
Value	13.4 (3.2)

Adverse events

Time frame: Baseline to end of treatment (Week 8). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Brexpiprazole	0 of 44 (0%)	22 of 44 (50%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32979560Krystal AD, Mittoux A, Lindsten A, Baker RA. Chronobiologic parameter changes in patients with major depressive disorder and sleep disturbance treated with adjunctive brexpiprazole: An open-label, flexible-dose, exploratory substudy. J Affect Disord. 2021 Jan 1;278:288-295. doi: 10.1016/j.jad.2020.09.026. Epub 2020 Sep 11.
Derived from this study: PubMed 27835722Krystal AD, Mittoux A, Meisels P, Baker RA. Effects of Adjunctive Brexpiprazole on Sleep Disturbances in Patients With Major Depressive Disorder: An Open-Label, Flexible-Dose, Exploratory Study. Prim Care Companion CNS Disord. 2016 Sep 8;18(5). doi: 10.4088/PCC.15m01914.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Email contact via H. Lundbeck A/S study director

LundbeckClinicalTrials@lundbeck.com

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Brexpiprazole in people with Sleep Disturbances, run by H. Lundbeck A/S.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Parameters (time frame: Baseline and Week 8). The study lists 26 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01942733, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2019.