A Study of Seltorexant as Adjunctive Therapy to Antidepre... | NCT04532749

NCT04532749

ID	Type	Description	Link
42847922MDD3002	Other Identifier	Janssen Research & Development, LLC
2020-000338-16	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Seltorexant	Experimental	Participants will receive Seltorexant orally once daily from Day 1 to Day 42 (until the end of Week 6).	Drug: Seltorexant
Placebo	Placebo Comparator	Participants will receive matching placebo tablets orally once daily from Day 1 to Day 42 (until the end of Week 6).	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Seltorexant	Drug	Participants will receive Seltorexant tablets.	Seltorexant

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Day 43 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	The MADRS was a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant treatment. The scale consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score was the sum of scores from individual question items, which ranged from 0 to 60, higher scores represented a more severe condition. Negative change in MADRS total score indicated improvement.	Baseline (Day 1), Day 43

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Day 43 in the MADRS Without Sleep Item (MADRS-WOSI) Total Score	The MADRS was a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant treatment. MADRS-WOSI was defined as the full MADRS without the sleep item. The MADRS-WOSI scale consisted of 9 items (apparent sadness, reported sadness, inner tension, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). Higher scores represented a more severe condition. MADRS-WOSI total score was the sum of scores from individual question items, which ranged from 0 to 54, higher scores represented a more severe condition. Negative change in MADRS total score indicated improvement.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Meet diagnostic and statistical manual of mental disorders-5th edition (DSM-5) diagnostic criteria for major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the structured clinical interview for DSM-5 Axis I disorders-clinical trials version (SCID-CT) diagnosed with first depressive episode prior to age 60. The duration of the current depressive episode must be less than or equal to (<=) 24 months
Have had an inadequate response to at least 1 but no more than 2 antidepressants, administered at an adequate dose and duration in the current episode of depression. The current antidepressant cannot be the first antidepressant treatment for the first lifetime episode of depression. An inadequate response is defined as less than (<) 50 percent (%) reduction but with some improvement (that is, improvement greater than [>] 0%) in depressive symptom severity with residual symptoms other than insomnia present, and overall good tolerability, as assessed by the MGH-ATRQ
Is receiving and tolerating well any one of the following selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) for depressive symptoms at screening, in any formulation and available in the participating country: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable dose (at therapeutic dose level) for at least 6 weeks, and for no greater than 18 months in the current episode
Have a hamilton depression rating scale (HDRS)-17 total score greater than or equal to (>=) 20 at the first screening interview, must not demonstrate a clinically significant improvement (that is [ie], an improvement of > 20 % on their HDRS-17 total score) from the first to the second independent HDRS-17 rating, and must have a HDRS-17 total score >= 18 at the second screening interview
Have a patient version of the Insomnia Severity Index (ISI) total score >=15 as well as a clinician version of the ISI total score >=15 at the second screening visit
Body mass index (BMI) between 18 and 40 kilogram per meter square (kg/m^2) inclusive (BMI=weight/height^2)
Participant must be medically stable on the basis of clinical laboratory tests performed at screening
Participant must be medically stable on the basis of the following: physical examination (including a brief neurological examination), vital signs (including blood pressure), and 12-lead electrocardiogram (ECG) performed at screening and baseline

Exclusion Criteria:

Has a recent (last 3 months) history of, or current signs and symptoms of, severe renal insufficiency (creatinine clearance [CrCl] < 30 milliliter per minute [mL/min]); clinically significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrine disorders and uncontrolled Type 1 or Type 2 diabetes mellitus
Has clinically significant hepatic disease as defined by >=2*Upper Limit of Normal (ULN) increase of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at screening
Has a history of treatment-resistant MDD, defined as a lack of response to 2 or more adequate antidepressant treatments in the current episode, as indicated by no or minimal (< 25% improvement in symptoms) when treated with an antidepressant of adequate dose (per massachusetts general hospital-antidepressant treatment response questionnaire [MGH-ATRQ]) and duration (at least 6 weeks).
Has history or current diagnosis of a psychotic disorder, bipolar disorder, intellectual disability, autism spectrum disorder, borderline personality disorder, or somatoform disorders
Has any significant primary sleep disorder, including but not limited to obstructive sleep apnea, restless leg syndrome, or parasomnias. Participants with insomnia disorder are allowed
Has a history of moderate to severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening

Contacts/Locations Module

Name	Affiliation	Role
Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Altea Research Institute		Phoenix	Arizona	85012	United States
Preferred Research Partners

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Seltorexant	During DB treatment phase, participants received seltorexant 20 milligrams (mg) tablet orally once daily from Day 1 to Day 42. Participants were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57) during the follow-up phase. Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 25, 2021	May 19, 2025

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

FG000107 subjects
FG001105 subjects

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Seltorexant	During DB treatment phase, participants received seltorexant 20 mg tablet orally once daily from Day 1 to Day 42. Participants were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57) during the follow-up phase. Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.
BG001	Placebo	During DB treatment phase, participants received placebo matching to seltorexant tablet orally once daily from Day 1 to Day 42. Participants were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57) during the follow-up phase. Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00050.2± 13.87 BG00148.8± 14.40 BG00249.5± 14.12

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00078 BG00183 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00038 BG00133 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

Argentina

Title	Measurements
	BG00013 BG00114 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to Day 43 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

The MADRS was a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant treatment. The scale consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score was the sum of scores from individual question items, which ranged from 0 to 60, higher scores represented a more severe condition. Negative change in MADRS total score indicated improvement.

The full analysis set 1 (FAS1) included all randomized participants who received at least 1 dose of study intervention in the DB phase and had baseline MADRS total score greater than or equal to (>=) 24 (per interactive web response system [IWRS]). Here 'N' (overall number of participants analyzed) refers to the number of participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

Units on a scale

Baseline (Day 1), Day 43

ID	Title	Description
OG000	Seltorexant	During DB treatment phase, participants received seltorexant 20 mg tablet orally once daily from Day 1 to Day 42. Participants were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57) during the follow-up phase. Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.
OG001	Placebo	During DB treatment phase, participants received placebo matching to seltorexant tablet orally once daily from Day 1 to Day 42. Participants were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57) during the follow-up phase. Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.

Units	Counts
Participants	OG000101 OG00189

Title

Denominators

Categories

Title	Measurements
	OG000-14.0± 10.46 OG001-13.1± 9.51

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Model Repeated Measures (MMRM)		=0.411		Least square (LS) mean difference	-1.2	Standard Error of the Mean	1.43	2-Sided	95	-4.00	1.64					Superiority

Secondary

Change From Baseline to Day 43 in the MADRS Without Sleep Item (MADRS-WOSI) Total Score

The MADRS was a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant treatment. MADRS-WOSI was defined as the full MADRS without the sleep item. The MADRS-WOSI scale consisted of 9 items (apparent sadness, reported sadness, inner tension, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). Higher scores represented a more severe condition. MADRS-WOSI total score was the sum of scores from individual question items, which ranged from 0 to 54, higher scores represented a more severe condition. Negative change in MADRS total score indicated improvement.

FAS1 included all randomized participants who received at least 1 dose of study intervention in the DB phase and had baseline MADRS total score >=24 (per IWRS). Here 'N' (overall number of participants analyzed) refers to the number of participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

Units on a scale

Baseline (Day 1), Day 43

ID	Title	Description
OG000	Seltorexant	During DB treatment phase, participants received seltorexant 20 mg tablet orally once daily from Day 1 to Day 42. Participants were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57) during the follow-up phase. Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.

Secondary

Change From Baseline to Day 43 in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD; Short Form 8a) T-score

PROMIS-SD Short Form 8a: static 8-item questionnaire, assessed self-perceptions of sleep initiation (2 items), quality of sleep (3 items), early morning feelings (2 items), worrying about sleep (1 item). Each question has 5 options ranged 1 to 5. The "direction" of responses was not same, sometimes "not at all" =more sleep disturbance; sometimes "not at all" =less sleep disturbance. Total raw score for short form with all questions answered was sum of values of response to each question, total score ranged 8 to 40. Lower scores=less sleep disturbance. Total raw score converted into T-score. T-score rescaled the raw score into standardized score with mean-50; SD-10. Negative changes in scores=improvement. Higher PROMIS T-score represents more concept measured. Negatively worded (like sleep disturbance), T-score of 60 was one SD worse than average. By comparison, T-score of 40 was one SD better than average. T-score of 50 or above was clinically significant level of sleep disturbance.

Posted

Mean

Standard Deviation

T-score

Baseline (Day 1), Day 43

ID	Title	Description
OG000	Seltorexant	During DB treatment phase, participants received seltorexant 20 mg tablet orally once daily from Day 1 to Day 42. Participants were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57) during the follow-up phase. Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.

Secondary

Change From Baseline to Day 43 in the 6-item MADRS (MADRS-6) Total Score

The 6-item MADRS was a clinician-administered scale designed to measure the core symptoms of depression severity and detected changes due to antidepressant intervention. It is a subset of MADRS (10-item). The MADRS-6 subscale score was the sum of scores for the following MADRS items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts. Each item was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), the overall score ranges from 0 to 36, higher scores represented a more severe condition. Negative changes in MADRS-6 total score indicate improvement.

Posted

Mean

Standard Deviation

Units on a scale

Baseline (Day 1), Day 43

ID	Title	Description
OG000	Seltorexant	During DB treatment phase, participants received seltorexant 20 mg tablet orally once daily from Day 1 to Day 42. Participants were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57) during the follow-up phase. Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.
OG001	Placebo

Secondary

Percentage of Participants Who Achieved Response on Depressive Symptoms Scale Based on MADRS Total Score at Day 43

Percentage of participants who achieved response on depressive symptoms scale based on MADRS total score at Day 43 were reported. Responders were defined as participants with a >=50 percent (%) improvement in the MADRS total score from baseline to a given timepoint. The MADRS was a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant treatment. The scale consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score was the sum of scores from individual question items, which ranged from 0 to 60, higher scores represented a more severe condition. Negative change in MADRS total score indicated improvement.

FAS1 included all randomized participants who received at least 1 dose of study intervention in the DB phase and had baseline MADRS total score >=24 (per IWRS).

Posted

Number

Percentage of participants

At Day 43

ID	Title	Description
OG000	Seltorexant	During DB treatment phase, participants received seltorexant 20 mg tablet orally once daily from Day 1 to Day 42. Participants were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57) during the follow-up phase. Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.

Secondary

Change From Baseline to Day 43 in Patient Health Questionnaire, 9-item (PHQ-9) Total Score

The PHQ-9 was a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) major depressive disorder (MDD) criteria. Each item was rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses were summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 was categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). Negative changes in PHQ-9 total score indicated improvement.

Posted

Mean

Standard Deviation

Units on a scale

Baseline (Day 1), Day 43

ID	Title	Description
OG000	Seltorexant	During DB treatment phase, participants received seltorexant 20 mg tablet orally once daily from Day 1 to Day 42. Participants were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57) during the follow-up phase. Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	DB Phase: Seltorexant	During DB treatment phase, participants received seltorexant 20 mg tablet orally once daily from Day 1 to Day 42.	107	0	107	14	107
EG001	DB Phase: Placebo	During DB treatment phase, participants received placebo matching to seltorexant tablet orally once daily from Day 1 to Day 42.	105	2	105	11	105
EG002	Follow-up Phase: Seltorexant	Participants who received seltorexant 20 mg and completed DB treatment phase entered follow-up phase and were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57). Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.	103	0	103	0	103
EG003	Follow-up Phase: Placebo	Participants who received placebo and completed DB treatment phase entered follow-up phase and were then followed up for safety up to 7 to 14 days after end of DB treatment at Day 43 (up to Day 57). Participants who discontinued study drug prior to Day 35 were encouraged to have additional follow-up visits every 2 weeks until Day 50 to 57.	98	0	98	0	98

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Depression	Psychiatric disorders	MedDRA Version 25.0	Non-systematic Assessment		EG0000 affected107 at risk EG0011 affected105 at risk EG0020 affected103 at risk EG0030 affected98 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA Version 25.0	Non-systematic Assessment		EG0000 affected107 at risk EG0011 affected105 at risk EG0020 affected103 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Headache	Nervous system disorders	MedDRA Version 25.0	Non-systematic Assessment		EG00014 affected107 at risk EG00111 affected105 at risk EG0020 affected103 at risk EG0030 affected98 at risk

ID	Term
D003865	Depressive Disorder, Major

ID	Term
C000655226	seltorexant

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders