Clinical trial NCT01942733: Study of Brexpiprazole as Adjunctive Treatment of Sleep Disturbances in Patients With Major Depressive Disorder
Official title: Interventional, Open-label, Flexible-dose, Exploratory Study of Brexpiprazole as Adjunctive Treatment of Sleep Disturbances in Patients With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sleep Disturbances
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2013-09-16
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria - at Screening:

* 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.

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).

Exclusion Criteria:

- 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.

Primary outcomes:
measure: Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Parameters
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Number of Awakenings (PSG NAW)
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 on Sleep Quality as Assessed by Polysomnographic Recorded (PSG) Sleep Efficiency (PSG SE)
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Sleep Efficiency (SE)
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M)
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 on Sleep Quality as Assessed by the Consensus Sleep Diary for Morning (CSD-M) Number of Awakenings (NAW)
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 in Sleep Architecture as Assessed With Polysomnography (Continued)
timeFrame: Baseline and Week 8
measure: Change From Baseline to Week 8 in ISI Total Score
timeFrame: Baseline and Week 8
measure: Change From Baseline to Week 8 on ESS Total Score
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 in Response Speed as Assessed Using a PVT Device
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 in Number of Lapses as Assessed Using a PVT Device
timeFrame: Baseline and Week 8
measure: Change From Baseline to Week 8 on BL-VAS-s (Evening) Score
timeFrame: Baseline and Week 8
measure: Change From Baseline to Week 8 on BL-VAS-s (Morning) Score
timeFrame: Baseline and Week 8
measure: Change From Baseline to Week 8 on BL-VAS-s Scores (Noon)
timeFrame: Baseline and Week 8
measure: Change From Baseline to Week 8 in CPFQ Total Score
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 in Circadian and Biological Rhythm
timeFrame: Baseline and Week 8
measure: Change From Baseline to Week 8 in MADRS Total Score
timeFrame: Baseline and Week 8
measure: Change From Baseline to Week 8 in CGI-S Score
timeFrame: Baseline and Week 8
measure: Percentage of MADRS Responders at Week 8
timeFrame: Week 8
measure: Percentage of MADRS Remitters at Week 8
timeFrame: Week 8
measure: Changes From Baseline to Week 8 on Sleep Quality as Assessed by Actigraphy (ACT) Parameters
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 on Sleep Efficiency (SE) as Assessed by Actigraphy (ACT)
timeFrame: Baseline and Week 8
measure: Changes From Baseline to Week 8 on Number of Awakenings (NAW) as Assessed by Actigraphy (ACT)
timeFrame: Baseline and Week 8
measure: Change From Baseline to Week 8 in BRIAN Total Score
timeFrame: Baseline and Week 8
measure: CGI-I Score at Week 8
timeFrame: Baseline and Week 8
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.