Depressive Disorder, Major
Conditions
Brief summary
The purpose of this study is to assess the dose-response relationship of 2 doses of JNJ-42847922 before interim analysis, and potentially 3 doses based on interim analysis results, compared to placebo as adjunctive therapy to an antidepressant drug in improving depressive symptoms in participants with Major Depressive Disorder (MDD) who have had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI); and to assess the safety and tolerability of JNJ-42847922 compared to placebo as adjunctive therapy to an antidepressant in participants with MDD.
Detailed description
The study will investigate the antidepressant effects of a range of doses of JNJ-42847922 (seltorexant) (versus placebo), as adjunctive treatment to antidepressant drugs for treatment of MDD, and will assess the safety and tolerability of JNJ-42847922. The study will be conducted in 3 phases: a screening phase (up to 4 weeks), a double-blind treatment phase (6 weeks), and a post-treatment follow-up phase (2 weeks). Efficacy, safety, pharmacokinetic, and biomarker evaluations will be performed in the study at defined timepoints. The duration of the study will be up to approximately 12 weeks (84 days).
Interventions
DRUGPlacebo
Participants will receive 2 placebo capsules matching JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).
DRUGJNJ-42847922
Participants will receive 2 capsules of JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Men or women of non-childbearing potential (WONCBP), aged 18 to 70 years (inclusive). A WONCBP is defined as: a).Postmenopausal: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. b). Permanently sterile: Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy. c). If reproductive status is questionable, additional evaluation should be considered * 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). In addition their major depressive episode must be deemed valid using the SCID Screening Questionnaire (SSQ) interview administered by remote, independent raters. The length of the current depressive episode must be less than or equal to (\<=) 18 months * Have had an inadequate response to at least 1 but no more than 3 antidepressants, administered at an adequate dose and duration in the current episode of depression, as measured by the Massachusetts General Hospital-Antidepressant Treatment Response Questionnaire (MGH-ATRQ). An inadequate response is defined as less than (\<)50 percent (%) reduction in depressive symptom severity, as assessed by the MGH-ATRQ. An adequate trial is defined as an antidepressant treatment for at least 4 weeks at or above the minimum therapeutic dose specified in the MGH-ATRQ, for any particular antidepressant. The inadequate response must include the participant's current antidepressant treatment * Participants receiving monotherapy treatment for depressive symptoms with one of the following selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants, in any formulation: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable dose (at or above the minimum therapeutic dose level) for at least 4 weeks, and for no greater than 12 months, at screening. Modification of an effective preexisting therapy should not be made for the explicit purpose of entering a subject into the study * Have a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater than or equal to (\>=)25 (performed by independent, centralized remote raters) at screening and must not demonstrate a clinically significant improvement (that is, an improvement of greater than \[\>\]20% on their MADRS total score) from the screening to baseline visit * Must be otherwise healthy on the basis of physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests performed at screening. If the results of the clinical laboratory tests are outside the normal reference ranges, the participant could be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator
Exclusion criteria
* Has a history of, or current signs and symptoms of, severe renal insufficiency (creatinine clearance \<30 milliliter per minute \[mL/min\]); moderate to severe hepatic insufficiency (Child-Pugh Score 7-9), significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic (including narcolepsy), hematologic, rheumatologic, immunologic or endocrine disorders (including uncontrolled hypo- or hyperthyroidism or diabetes, or insulin-dependent diabetes mellitus). Participants with non-insulin dependent diabetes mellitus who are well-controlled (hemoglobin A1C \[HbA1C\] \<=7.5% and fasting glucose \<126 milligram per deciliter \[mg/dL\] at screening) could be eligible to participate if otherwise medically healthy, and if on a stable regimen of glucose-lowering medications for at least 2 months prior to screening * Has signs and symptoms of Cushing's Disease, Addison's Disease, primary amenorrhea, or other evidence of significant medical disorders of the hypothalamic-pituitary-adrenal (HPA) axis * Has a history of lack of response to 3 or more adequate antidepressant treatments, as indicated by no or minimal (\<= 25% improvement in symptoms) when treated with an antidepressant of adequate dose (per MGH-ATRQ) and duration (at least 4 weeks) * Has history or current diagnosis of a psychotic disorder, bipolar disorder, mental retardation, autism spectrum disorder, or borderline personality disorder, somatoform disorders, chronic fatigue syndrome or fibromyalgia * Has any significant primary sleep disorder, including but not limited to obstructive sleep apnea, restless leg syndrome, or parasomnias
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physician Withdrawal Checklist-20 (PWC-20) Total Score From Day 49 to Day 56 | Day 49 to Day 56 | Intensity of discontinuation symptoms was assessed (for example: underlying depression; anxiety-nervousness; dysphoric mood/depression; difficulty concentrating; weakness; fatigue-lethargy-lack of energy; irritability), using the Physician Withdrawal Checklist (PWC-20) administered by a trained clinician/rater. Symptoms are rated on a scale 0 (No symptom present) and 3 (severe symptoms). Total scores range from 0 to 24 calculated by adding the scores of following 8 items: Nausea-Vomiting, Diarrhea, Poor Coordination, Diaphoresis, Tremor-Tremulousness, Dizziness-Lightheadedness, Increased Acuity Sound Smell Touch, Paresthesias. Higher scores indicating more severe symptoms. |
| Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability | Up to Week 8 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between the initial administration of study drug and 2 days after the last administration of study drug. |
| Percentage of Participants With Clinically Significant Laboratory Abnormalities | Up to Week 8 | Percentage of participants with clinically significant laboratory abnormalities were reported which included Gamma-glutamyl transferase (GGT), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Albumin , bicarbonate, bilirubin, calcium, chloride, cholesterol, creatinine, direct bilirubin, glucose, high density lipoprotein (HDL) cholesterol, hemoglobin A1C, low density lipoprotein (LDL) cholesterol, phosphate, potassium, protein, sodium, triglycerides, urate, and urea nitrogen. |
| Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Baseline and Day 42 | Change from baseline in vital signs (SBP and DBP) at Day 42 was reported. |
| Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Baseline and Endpoint (Week 6) | Change from baseline in vital signs (SBP and DBP) at endpoint was reported. |
| Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8 | Baseline and Day 8 | Change from baseline in vital sign (PR) at Day 8 was reported. |
| Change From Baseline in Vital Sign (PR) at Day 22 | Baseline and Day 22 | Change from baseline in vital sign (PR) at Day 22 was reported. |
| Change From Baseline in Vital Sign (PR) at Day 42 | Baseline and Day 42 | Change from baseline in vital sign (PR) at Day 42 was reported. |
| Change From Baseline in Vital Sign (PR) at Endpoint (Week 6) | Baseline and Endpoint (Week 6) | Change from baseline in vital sign (PR) at endpoint (Week 6) was reported. |
| Change From Baseline in Vital Sign (Temperature) at Day 8 | Baseline and Day 8 | Change from baseline in vital Sign (temperature) at Day 8 was reported. |
| Change From Baseline in Vital Sign (Temperature) at Day 22 | Baseline and Day 22 | Change from baseline in vital Sign (temperature) at Day 22 was reported. |
| Change From Baseline in Vital Sign (Temperature) at Day 42 | Baseline and Day 42 | Change from baseline in vital Sign (temperature) at Day 42 was reported. |
| Change From Baseline in Vital Sign (Temperature) at Endpoint (Week 6) | Baseline and Endpoint (Week 6) | Change from baseline in vital Sign (temperature) at endpoint (Week 6) was reported. |
| Change From Baseline in Physical Examination (Waist Circumference) at Day 42 | Baseline and Day 42 | Change from baseline in physical examination (waist circumference) was reported. |
| Change From Baseline in Physical Examination (Body Weight) at Day 42 | Baseline and Day 42 | Change from baseline in physical examination (body weight) was reported. |
| Change From Baseline in Physical Examination (Body Mass Index [BMI]) at Day 42 | Baseline and Day 42 | Change from baseline in physical examination (BMI) was reported. |
| Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | Up to Week 6 | Percentage of participants with treatment-emergent abnormal ECG values (Heart rate less than or equal to \[\<=\] 50 or greater than or equal to \[\>=\] 100 beats per minute \[bpm\], PR interval \<=120 or \>=200 milliseconds \[msec\], QRS interval \<=60 or \>=120 msec, and QT interval \<=200 or \>=500 msec) outside pre-defined limits were reported. |
| Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | Up to Week 8 | C-SSRS is a clinician-rated instrument that reports severity of both suicidal ideation and behavior. Suicidal ideation was classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods \[not plan\] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior), 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), and 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes. Minimum total score 0, maximum total score 5; higher total scores indicate more suicidal ideation and/or suicidal behavior. If no events qualify for score of 1 to 10, score of 0 was assigned (0= no event that can be assessed on the basis of C-SSRS). Higher scores indicate greater severity. |
| Change From Baseline in Sexual Functioning as Measured by Arizona Sexual Experiences Scale (ASEX) Score at Day 42 | Baseline and Day 42 | Effect on sexual functioning was assessed using the ASEX score. The ASEX is a five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each of the 5 items is rated on a 6-point scale, ranging from 1 to 6. The 5 items are summed to create a total score, ranging from 5 to 30, with the higher scores indicating more sexual dysfunction. |
| Physician Withdrawal Checklist-20 (PWC-20) Total Score at Day 43 | Day 43 | Intensity of discontinuation symptoms was assessed (for example: underlying depression; anxiety-nervousness; dysphoric mood/depression; difficulty concentrating; weakness; fatigue-lethargy-lack of energy; irritability), using the Physician Withdrawal Checklist (PWC-20) administered by a trained clinician/rater. Symptoms are rated on a scale 0 (No symptom present) and 3 (severe symptoms). Total scores range from 0 to 24 calculated by adding the scores of following 8 items: Nausea-Vomiting, Diarrhea, Poor Coordination, Diaphoresis, Tremor-Tremulousness, Dizziness-Lightheadedness, Increased Acuity Sound Smell Touch, Paresthesias. Higher scores indicating more severe symptoms. |
| Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Baseline and Day 22 | Change from baseline in vital signs (SBP and DBP) at Day 22 was reported. |
| Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Baseline and Day 8 | Change from baseline in vital signs (SBP and DBP) at Day 8 was reported. |
| Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline to Week 6 | MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in ISI Total Score at DB Endpoint (Up to Week 6) | Baseline and DB Endpoint (Up to Week 6) | The ISI is a commonly used, 7-item psychometrically validated measure used to rate insomnia. Each item is scored 0 (no problem) to 4 (very big problem) with total between 0-28 which is calculated by adding the scores of all 7 items (absence of insomnia \[0-7\]; sub-threshold insomnia \[8-14\]; moderate insomnia \[15-21\]; and severe insomnia \[22-28\]). The change in ISI total score from baseline at DB endpoint was evaluated. Negative change in score indicates improvement. |
| Percentage of Participants With Response on Depressive Symptoms Scale Based on MADRS Total Score | Day 42 | Responders are defined as participants with a \>=50 percent (%) improvement in the MADRS total score from baseline to a given timepoint. MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. Participants with missing values at a given time point were imputed as non-responders. |
| Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | Day 42 | Participants with a MADRS total score of less than or equal to (\<=) 8, \<=10, and \<=12 at a given time point were considered as remitters. MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. Participants with missing values at a given time point were imputed as non-responders. |
| Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Day 42 | Baseline and Day 42 | HAM-A is a 14-item scale designed to measure anxiety in individuals. Each question reflects a symptom of anxiety and physical as well as mental symptoms are represented. Each of the 14-items in the scale is scored on a 5-point scale, ranging from 0 (a complete lack of that symptom) to 4 (a very severe show of anxiety with that symptom). The total score ranges from 0 to 56 which is calculated by adding the scores of all 14 items, where 0-13 indicates normal range, 14-17 indicates mild severity, 18 -24: mild to moderate severity, 25 -30: moderate to severe, and \>=31: severe. Higher score indicates worsening. Negative change in score indicates improvement. |
| Percentage of Participants With Response on Anxiety Symptoms Scale Based on HAM-A Total Score | Day 42 | Participants with a \>=50 percent improvement in the HAM-A total score from baseline at a given timepoint were considered as responders. HAM-A is a 14-item scale designed to measure anxiety in individuals. Each question reflects a symptom of anxiety and physical as well as mental symptoms are represented. Each of the 14-items in the scale is scored on a 5-point scale, ranging from 0 (a complete lack of that symptom) to 4 (a very severe show of anxiety with that symptom). The total score ranges from 0 to 56 which is calculated by adding the scores of all 14 items, where 0-13 indicates normal range, 14-17 indicates mild severity, 18 -24: mild to moderate severity, 25 -30: moderate to severe, and \>=31: severe. Higher score indicates worsening. Participants with missing values at a given time point were imputed as non-responders. |
| Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at DB Endpoint (Up to Week 6) | Baseline and DB Endpoint (Up to Week 6) | The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S is a 7-point global assessment scale that measures the clinician's impression of the severity of illness exhibited by a participant, rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. Higher scores indicate worsening. Negative change in score indicates improvement. |
| Change From Baseline in the Sheehan Disability Scale (SDS) Score at Day 42 | Baseline and Day 42 | The SDS is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. The first 3 items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0-10 rating scale. The scores for the first 3 items are summed to create a total score of 0-30, where a higher score indicates greater impairment. It also has 1 item on days lost from school or work and 1 item on days when underproductive. Negative change in score indicates improvement. |
| Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress | Baseline and Day 42 | MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. Negative change in score indicates improvement. |
| Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Baseline, Days 8, 22 and 42 | Exposure on the hypothalamic-pituitary-adrenal (HPA) axis in participants with MDD was evaluated by assessing change in salivary cortisol levels. |
| Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Day 1: Between 0.25 hours (h) to 1.5 hour, 2 to 4 hours, and 6 to 8 hours post-dose; Day 8 (morning): 6 to 12 hours post evening dose of Day 7 | Plasma concentrations of Seltorexant and its metabolites (M12 and M16) over time were reported. |
| Change From Baseline in Depressive Symptoms Using the Patient Health Questionnaire 9-Item (PHQ-9) at DB Endpoint (Up to Week 6) | Baseline and DB Endpoint (Up to Week 6) | The PHQ-9 is a 9-item, Patient Reported Outcome (PRO) 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 is 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 participants item responses are 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 is categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19) and Severe (20-27). |
| Change From Baseline in Anhedonia Using the Snaith-Hamilton Pleasure Scale (SHAPS) Score at DB Endpoint (Up to Week 6) | Baseline and DB Endpoint (Up to Week 6) | The SHAPS is a 14-item, self-report instrument to assess hedonic capacity in adults with MDD. Each of the items has a set of 4 response categories-Definitely Agree (=1), Agree (=2), Disagree (=3), and Definitely Disagree (=4). A total score is created with either of the Disagree responses receiving a score of 1 and either of the Agree responses receiving a score of 0. The participants item responses are summed to provide a total score ranging from 0 to 14. A higher total SHAPS score indicates higher levels of current anhedonia. |
| Change From Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form at DB Endpoint (Up to Week 6) | Baseline and DB Endpoint (Up to Week 6) | The PROMIS-SD Short Form subscale consists of a static 8 item questionnaire. It assesses the concepts of sleep initiation (2 items), quality of sleep (3 items), early morning feelings (2 items) and worrying about sleep (1 item). Responses to each of the 8 items range from 1 to 5, and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS-SD indicate more of the concept measured (disturbed sleep). Negative change in score indicates improvement. |
| Change From Baseline in Fatigue Using the Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Short Form Subscale Score at DB Endpoint (Up to Week 6) | Baseline and DB Endpoint (Up to Week 6) | The PROMIS-Fatigue Short Form subscale consists of a static 8 item questionnaire. It assesses a range of symptoms from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Ratings are done on a 5-item Likert scale ranging from 0 (not at all) to 5 (very much) or 0 (never) to 5(always) depending upon the question answered. Higher scores on the PROMIS-F indicate more of the concept measured (fatigue). Negative change in score indicates improvement. |
| Change From Baseline in Severity of Depression Using the Patient Global Impression-Severity (PGI-S) Score at DB Endpoint (Up to Week 6) | Baseline and DB Endpoint (Up to Week 6) | The PGI-S is a self-report scale to measure severity of illness (1=none, 2=mild, 3=moderate, 4=severe). Higher score indicates more illness severity. Negative change in score indicates improvement. |
| Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Heath State Index Total Score at DB Endpoint (Up to Week 6) | Baseline and DB Endpoint (Up to Week 6) | EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). The responses to 5 EQ-5D-5L dimensions were scored using a utility-weighted algorithm to derive an EQ-5D-5L health status index score between 0 (death) to 100 (full health). |
| Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Total Score at Endpoint (Up to Week 6) | Baseline and Endpoint (up to Week 6) | The EQ-5D-5L is a standardized instrument for use as a measure of health outcome, primarily designed for self-completion by respondents. It consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). EQ-5D-5L (describing and valuing health-related quality of life) descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the participant's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. Higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. EQ-VAS self-rating records respondent's own assessment of his/her overall health status at time of completion, on scale of 0 (worst health you can imagine) to 100 (best health you can imagine). |
| Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Baseline and DB Endpoint (Up to Week 6) | The WLQ is to assess the on-the-job impact of chronic health problems and/or treatment (work limitations) in adults. It is a 8-item questionnaire self-report rating scale developed to measure the on-the-job impact of chronic health problems and/or treatment (work limitations). It comprises five dimensions of limitations: handling time, physical, mental-interpersonal, productivity loss and output demands. Participants respond to each item with options ranging from 'Almost all of the time' to 'none of the time', or 'Does not apply to my job'. Each dimension of limitations have a scale score ranging from 0 to 100 with lower score indicating low level of work limitations. |
| Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42 | Baseline and Day 42 | MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. The ISI has 7 questions, each rated on a 5-point Likert scale ranging from 0 to 4. The total score is calculated as the sum of the 7 items ranging from 0 to 28. Higher scores represent a more severe condition. |
Countries
Bulgaria, Finland, France, Germany, Japan, Russia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants in the double-blind treatment period received seltorexant matching placebo capsule once daily orally from Day 1 to Day 41 (Week 6). Participants had a follow-up visit within 7 to 14 days after double-blind treatment period. During the follow-up phase, participants were followed-up for the safety assessments on Day 43 (Week 7). | 137 |
| Seltorexant 10 mg Participants in the double-blind treatment period received seltorexant 10 milligrams (mg) capsules once daily orally from Day 1 to Day 41 (Week 6). Participants had a follow-up visit within 7 to 14 days after double-blind treatment period. During the follow-up phase, participants were followed-up for the safety assessments on Day 43 (Week 7). | 33 |
| Seltorexant 20 mg Participants in the double-blind treatment period received seltorexant 20 mg capsules once daily orally from Day 1 to Day 41 (Week 6). Participants had a follow-up visit within 7 to 14 days after double-blind treatment period. During the follow-up phase, participants were followed-up for the safety assessments on Day 43 (Week 7). | 61 |
| Seltorexant 40 mg Participants in the double-blind treatment period received seltorexant 40 mg capsules (2\*20 mg capsules) once daily orally from Day 1 to Day 41 (Week 6). Participants had a follow-up visit within 7 to 14 days after double-blind treatment period. During the follow-up phase, participants were followed-up for the safety assessments on Day 43 (Week 7). | 52 |
| Total | 283 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Treatment Period (6 Weeks) | Adverse Event | 2 | 1 | 1 | 4 |
| Double-blind Treatment Period (6 Weeks) | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Double-blind Treatment Period (6 Weeks) | Lost to Follow-up | 1 | 0 | 2 | 0 |
| Double-blind Treatment Period (6 Weeks) | Non-Compliance with Study Drug | 2 | 1 | 0 | 1 |
| Double-blind Treatment Period (6 Weeks) | Other | 4 | 0 | 1 | 0 |
| Double-blind Treatment Period (6 Weeks) | Protocol Violation | 2 | 2 | 0 | 0 |
| Double-blind Treatment Period (6 Weeks) | Received a Disallowed Concomitant Treatment | 0 | 0 | 1 | 0 |
| Double-blind Treatment Period (6 Weeks) | Withdrawal by Subject | 3 | 2 | 3 | 2 |
| Follow-up Phase (2 Weeks) | Other | 4 | 4 | 6 | 3 |
Baseline characteristics
| Characteristic | Placebo | Seltorexant 10 mg | Seltorexant 20 mg | Seltorexant 40 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 49.6 years STANDARD_DEVIATION 11.71 | 49.4 years STANDARD_DEVIATION 15.31 | 48.5 years STANDARD_DEVIATION 13.56 | 48.3 years STANDARD_DEVIATION 10.52 | 49.1 years STANDARD_DEVIATION 12.34 |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 131 Participants | 29 Participants | 59 Participants | 51 Participants | 270 Participants |
| Age, Customized From 65 to 84 years | 6 Participants | 4 Participants | 2 Participants | 1 Participants | 13 Participants |
| Race/Ethnicity, Customized Asian | 20 Participants | 3 Participants | 9 Participants | 8 Participants | 40 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 1 Participants | 2 Participants | 5 Participants | 19 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 15 Participants | 1 Participants | 5 Participants | 7 Participants | 28 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 120 Participants | 31 Participants | 53 Participants | 42 Participants | 246 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 105 Participants | 29 Participants | 50 Participants | 39 Participants | 223 Participants |
| Region of Enrollment BULGARIA | 35 Participants | 2 Participants | 17 Participants | 12 Participants | 66 Participants |
| Region of Enrollment FINLAND | 3 Participants | 1 Participants | 1 Participants | 5 Participants | 10 Participants |
| Region of Enrollment GERMANY | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Region of Enrollment JAPAN | 18 Participants | 3 Participants | 8 Participants | 8 Participants | 37 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 18 Participants | 16 Participants | 8 Participants | 3 Participants | 45 Participants |
| Region of Enrollment UKRAINE | 22 Participants | 6 Participants | 6 Participants | 5 Participants | 39 Participants |
| Region of Enrollment UNITED STATES | 41 Participants | 4 Participants | 20 Participants | 18 Participants | 83 Participants |
| Sex: Female, Male Female | 74 Participants | 20 Participants | 30 Participants | 28 Participants | 152 Participants |
| Sex: Female, Male Male | 63 Participants | 13 Participants | 31 Participants | 24 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 137 | 0 / 33 | 0 / 61 | 0 / 52 | 0 / 137 | 0 / 33 | 0 / 61 | 0 / 52 |
| other Total, other adverse events | 22 / 137 | 5 / 33 | 11 / 61 | 12 / 52 | 1 / 137 | 0 / 33 | 0 / 61 | 1 / 52 |
| serious Total, serious adverse events | 1 / 137 | 0 / 33 | 0 / 61 | 0 / 52 | 0 / 137 | 0 / 33 | 0 / 61 | 0 / 52 |
Outcome results
Primary
Change From Baseline in Physical Examination (Body Mass Index [BMI]) at Day 42
Change from baseline in physical examination (BMI) was reported.
Time frame: Baseline and Day 42
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Physical Examination (Body Mass Index [BMI]) at Day 42 | 0.07 kilograms per meter square (kg/m^2) | Standard Deviation 0.85 |
| Seltorexant 10 mg | Change From Baseline in Physical Examination (Body Mass Index [BMI]) at Day 42 | 0.01 kilograms per meter square (kg/m^2) | Standard Deviation 0.662 |
| Seltorexant 20 mg | Change From Baseline in Physical Examination (Body Mass Index [BMI]) at Day 42 | 0.02 kilograms per meter square (kg/m^2) | Standard Deviation 0.553 |
| Seltorexant 40 mg | Change From Baseline in Physical Examination (Body Mass Index [BMI]) at Day 42 | 0.22 kilograms per meter square (kg/m^2) | Standard Deviation 0.715 |
Primary
Change From Baseline in Physical Examination (Body Weight) at Day 42
Change from baseline in physical examination (body weight) was reported.
Time frame: Baseline and Day 42
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Physical Examination (Body Weight) at Day 42 | 0.19 Kilograms (kg) | Standard Deviation 2.373 |
| Seltorexant 10 mg | Change From Baseline in Physical Examination (Body Weight) at Day 42 | 0.01 Kilograms (kg) | Standard Deviation 1.889 |
| Seltorexant 20 mg | Change From Baseline in Physical Examination (Body Weight) at Day 42 | 0.05 Kilograms (kg) | Standard Deviation 1.563 |
| Seltorexant 40 mg | Change From Baseline in Physical Examination (Body Weight) at Day 42 | 0.61 Kilograms (kg) | Standard Deviation 1.946 |
Primary
Change From Baseline in Physical Examination (Waist Circumference) at Day 42
Change from baseline in physical examination (waist circumference) was reported.
Time frame: Baseline and Day 42
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Physical Examination (Waist Circumference) at Day 42 | 0.31 centimeters (cm) | Standard Deviation 2.778 |
| Seltorexant 10 mg | Change From Baseline in Physical Examination (Waist Circumference) at Day 42 | -0.50 centimeters (cm) | Standard Deviation 1.972 |
| Seltorexant 20 mg | Change From Baseline in Physical Examination (Waist Circumference) at Day 42 | 0.00 centimeters (cm) | Standard Deviation 3.523 |
| Seltorexant 40 mg | Change From Baseline in Physical Examination (Waist Circumference) at Day 42 | -0.48 centimeters (cm) | Standard Deviation 9.498 |
Primary
Change From Baseline in Sexual Functioning as Measured by Arizona Sexual Experiences Scale (ASEX) Score at Day 42
Effect on sexual functioning was assessed using the ASEX score. The ASEX is a five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each of the 5 items is rated on a 6-point scale, ranging from 1 to 6. The 5 items are summed to create a total score, ranging from 5 to 30, with the higher scores indicating more sexual dysfunction.
Time frame: Baseline and Day 42
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sexual Functioning as Measured by Arizona Sexual Experiences Scale (ASEX) Score at Day 42 | -1.4 score on a scale | Standard Deviation 4.55 |
| Seltorexant 10 mg | Change From Baseline in Sexual Functioning as Measured by Arizona Sexual Experiences Scale (ASEX) Score at Day 42 | -2.2 score on a scale | Standard Deviation 3.62 |
| Seltorexant 20 mg | Change From Baseline in Sexual Functioning as Measured by Arizona Sexual Experiences Scale (ASEX) Score at Day 42 | -2.4 score on a scale | Standard Deviation 4.55 |
| Seltorexant 40 mg | Change From Baseline in Sexual Functioning as Measured by Arizona Sexual Experiences Scale (ASEX) Score at Day 42 | -2.5 score on a scale | Standard Deviation 4.94 |
Primary
Change From Baseline in Vital Sign (PR) at Day 22
Change from baseline in vital sign (PR) at Day 22 was reported.
Time frame: Baseline and Day 22
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign (PR) at Day 22 | Standing PR | 1.4 Beats per minute | Standard Deviation 7.57 |
| Placebo | Change From Baseline in Vital Sign (PR) at Day 22 | Supine PR | 1.5 Beats per minute | Standard Deviation 7.61 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (PR) at Day 22 | Supine PR | -0.7 Beats per minute | Standard Deviation 7.31 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (PR) at Day 22 | Standing PR | 0.7 Beats per minute | Standard Deviation 7.36 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (PR) at Day 22 | Standing PR | 1.5 Beats per minute | Standard Deviation 8.27 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (PR) at Day 22 | Supine PR | 2.8 Beats per minute | Standard Deviation 7.94 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (PR) at Day 22 | Standing PR | 0.3 Beats per minute | Standard Deviation 9.59 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (PR) at Day 22 | Supine PR | 0.9 Beats per minute | Standard Deviation 10.55 |
Primary
Change From Baseline in Vital Sign (PR) at Day 42
Change from baseline in vital sign (PR) at Day 42 was reported.
Time frame: Baseline and Day 42
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign (PR) at Day 42 | Standing PR | 0.8 Beats per minute | Standard Deviation 7.99 |
| Placebo | Change From Baseline in Vital Sign (PR) at Day 42 | Supine PR | 0.3 Beats per minute | Standard Deviation 8.16 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (PR) at Day 42 | Supine PR | -2.8 Beats per minute | Standard Deviation 8.67 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (PR) at Day 42 | Standing PR | -1.4 Beats per minute | Standard Deviation 9.35 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (PR) at Day 42 | Standing PR | 1.5 Beats per minute | Standard Deviation 8.99 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (PR) at Day 42 | Supine PR | 2.4 Beats per minute | Standard Deviation 9.01 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (PR) at Day 42 | Standing PR | -0.6 Beats per minute | Standard Deviation 9.04 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (PR) at Day 42 | Supine PR | -0.6 Beats per minute | Standard Deviation 9.71 |
Primary
Change From Baseline in Vital Sign (PR) at Endpoint (Week 6)
Change from baseline in vital sign (PR) at endpoint (Week 6) was reported.
Time frame: Baseline and Endpoint (Week 6)
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure. Endpoint (DB) values are from the last measurement within the double-blind period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign (PR) at Endpoint (Week 6) | Standing PR | 0.4 Beats per minute | Standard Deviation 8.4 |
| Placebo | Change From Baseline in Vital Sign (PR) at Endpoint (Week 6) | Supine PR | 0.2 Beats per minute | Standard Deviation 8.16 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (PR) at Endpoint (Week 6) | Supine PR | -2.4 Beats per minute | Standard Deviation 8.97 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (PR) at Endpoint (Week 6) | Standing PR | -1.6 Beats per minute | Standard Deviation 9.27 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (PR) at Endpoint (Week 6) | Standing PR | 2.1 Beats per minute | Standard Deviation 9.34 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (PR) at Endpoint (Week 6) | Supine PR | 2.4 Beats per minute | Standard Deviation 8.78 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (PR) at Endpoint (Week 6) | Standing PR | -0.5 Beats per minute | Standard Deviation 9.11 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (PR) at Endpoint (Week 6) | Supine PR | -0.5 Beats per minute | Standard Deviation 9.6 |
Primary
Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8
Change from baseline in vital sign (PR) at Day 8 was reported.
Time frame: Baseline and Day 8
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8 | Standing PR | -0.1 Beats per minute | Standard Deviation 7.95 |
| Placebo | Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8 | Supine PR | 0 Beats per minute | Standard Deviation 7.15 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8 | Supine PR | -1.2 Beats per minute | Standard Deviation 7.16 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8 | Standing PR | -0.7 Beats per minute | Standard Deviation 7.07 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8 | Standing PR | 0.9 Beats per minute | Standard Deviation 9.17 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8 | Supine PR | 0.5 Beats per minute | Standard Deviation 6.23 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8 | Standing PR | 1.3 Beats per minute | Standard Deviation 9.21 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8 | Supine PR | 1.7 Beats per minute | Standard Deviation 9.32 |
Primary
Change From Baseline in Vital Signs (SBP and DBP) at Day 22
Change from baseline in vital signs (SBP and DBP) at Day 22 was reported.
Time frame: Baseline and Day 22
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Standing DBP | 0.0 mmHg | Standard Deviation 6.67 |
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Standing SBP | 0.2 mmHg | Standard Deviation 7.01 |
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Supine DBP | -0.4 mmHg | Standard Deviation 6.81 |
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Supine SBP | 0.8 mmHg | Standard Deviation 8.14 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Standing SBP | -1.2 mmHg | Standard Deviation 6.55 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Supine DBP | -1.8 mmHg | Standard Deviation 6.7 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Supine SBP | 0.3 mmHg | Standard Deviation 4.76 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Standing DBP | -1.2 mmHg | Standard Deviation 5.92 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Supine DBP | -0.2 mmHg | Standard Deviation 7.41 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Standing SBP | -2.7 mmHg | Standard Deviation 9.62 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Supine SBP | -0.9 mmHg | Standard Deviation 10.78 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Standing DBP | -0.4 mmHg | Standard Deviation 6.9 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Supine SBP | 2.2 mmHg | Standard Deviation 10.08 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Standing SBP | 1.6 mmHg | Standard Deviation 11.29 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Standing DBP | 2.4 mmHg | Standard Deviation 7.42 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 22 | Supine DBP | 2.6 mmHg | Standard Deviation 6.81 |
Primary
Change From Baseline in Vital Signs (SBP and DBP) at Day 42
Change from baseline in vital signs (SBP and DBP) at Day 42 was reported.
Time frame: Baseline and Day 42
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Standing DBP | -0.5 mmHg | Standard Deviation 6.22 |
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Standing SBP | -0.5 mmHg | Standard Deviation 7.99 |
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Supine DBP | -0.6 mmHg | Standard Deviation 7.1 |
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Supine SBP | 0.6 mmHg | Standard Deviation 8.88 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Standing SBP | 1.1 mmHg | Standard Deviation 7.92 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Supine DBP | -1.6 mmHg | Standard Deviation 9.23 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Supine SBP | -0.5 mmHg | Standard Deviation 10 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Standing DBP | 0.3 mmHg | Standard Deviation 9.16 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Supine DBP | 0.0 mmHg | Standard Deviation 8.31 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Standing SBP | -3.2 mmHg | Standard Deviation 10.57 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Supine SBP | -1.3 mmHg | Standard Deviation 10.85 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Standing DBP | -0.8 mmHg | Standard Deviation 6.75 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Supine SBP | 1.9 mmHg | Standard Deviation 8.35 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Standing SBP | 2.0 mmHg | Standard Deviation 9.9 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Standing DBP | 2.9 mmHg | Standard Deviation 7.96 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Day 42 | Supine DBP | 2.1 mmHg | Standard Deviation 7.5 |
Primary
Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6)
Change from baseline in vital signs (SBP and DBP) at endpoint was reported.
Time frame: Baseline and Endpoint (Week 6)
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure. Endpoint (double-blind \[DB\]) values are from the last measurement within the double-blind period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Standing DBP | -0.3 mmHg | Standard Deviation 6.29 |
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Standing SBP | -0.3 mmHg | Standard Deviation 8.33 |
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Supine DBP | -0.4 mmHg | Standard Deviation 7.08 |
| Placebo | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Supine SBP | 0.6 mmHg | Standard Deviation 8.81 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Standing SBP | 1.0 mmHg | Standard Deviation 7.42 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Supine DBP | -1.4 mmHg | Standard Deviation 9.34 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Supine SBP | -0.3 mmHg | Standard Deviation 9.38 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Standing DBP | 0.6 mmHg | Standard Deviation 8.98 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Supine DBP | 0.2 mmHg | Standard Deviation 8.35 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Standing SBP | -3.1 mmHg | Standard Deviation 10.29 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Supine SBP | -1.4 mmHg | Standard Deviation 10.52 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Standing DBP | -0.6 mmHg | Standard Deviation 6.78 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Supine SBP | 1.6 mmHg | Standard Deviation 8.58 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Standing SBP | 1.8 mmHg | Standard Deviation 9.89 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Standing DBP | 2.8 mmHg | Standard Deviation 7.79 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6) | Supine DBP | 2.3 mmHg | Standard Deviation 7.39 |
Primary
Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8
Change from baseline in vital signs (SBP and DBP) at Day 8 was reported.
Time frame: Baseline and Day 8
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Standing DBP | -0.7 millimeters of mercury (mmHg) | Standard Deviation 6.29 |
| Placebo | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Standing SBP | -0.4 millimeters of mercury (mmHg) | Standard Deviation 8.16 |
| Placebo | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Supine DBP | -0.8 millimeters of mercury (mmHg) | Standard Deviation 6.32 |
| Placebo | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Supine SBP | 0.1 millimeters of mercury (mmHg) | Standard Deviation 8.19 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Standing SBP | -0.8 millimeters of mercury (mmHg) | Standard Deviation 7.19 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Supine DBP | -0.9 millimeters of mercury (mmHg) | Standard Deviation 6.19 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Supine SBP | 1.6 millimeters of mercury (mmHg) | Standard Deviation 6.56 |
| Seltorexant 10 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Standing DBP | -0.5 millimeters of mercury (mmHg) | Standard Deviation 5.22 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Supine DBP | 2.3 millimeters of mercury (mmHg) | Standard Deviation 6.14 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Standing SBP | 0.2 millimeters of mercury (mmHg) | Standard Deviation 8.17 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Supine SBP | 1.5 millimeters of mercury (mmHg) | Standard Deviation 9.57 |
| Seltorexant 20 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Standing DBP | 0.7 millimeters of mercury (mmHg) | Standard Deviation 5.86 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Supine SBP | 0.5 millimeters of mercury (mmHg) | Standard Deviation 10.19 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Standing SBP | 0.3 millimeters of mercury (mmHg) | Standard Deviation 9.71 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Standing DBP | 0.9 millimeters of mercury (mmHg) | Standard Deviation 6.41 |
| Seltorexant 40 mg | Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8 | Supine DBP | 1.2 millimeters of mercury (mmHg) | Standard Deviation 6.67 |
Primary
Change From Baseline in Vital Sign (Temperature) at Day 22
Change from baseline in vital Sign (temperature) at Day 22 was reported.
Time frame: Baseline and Day 22
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign (Temperature) at Day 22 | -0.02 Celsius | Standard Deviation 0.299 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (Temperature) at Day 22 | -0.01 Celsius | Standard Deviation 0.242 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (Temperature) at Day 22 | -0.02 Celsius | Standard Deviation 0.332 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (Temperature) at Day 22 | 0.02 Celsius | Standard Deviation 0.392 |
Primary
Change From Baseline in Vital Sign (Temperature) at Day 42
Change from baseline in vital Sign (temperature) at Day 42 was reported.
Time frame: Baseline and Day 42
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign (Temperature) at Day 42 | 0.02 Celsius | Standard Deviation 0.326 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (Temperature) at Day 42 | -0.04 Celsius | Standard Deviation 0.291 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (Temperature) at Day 42 | -0.05 Celsius | Standard Deviation 0.223 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (Temperature) at Day 42 | 0.05 Celsius | Standard Deviation 0.445 |
Primary
Change From Baseline in Vital Sign (Temperature) at Day 8
Change from baseline in vital Sign (temperature) at Day 8 was reported.
Time frame: Baseline and Day 8
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign (Temperature) at Day 8 | -0.01 Celsius | Standard Deviation 0.324 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (Temperature) at Day 8 | -0.05 Celsius | Standard Deviation 0.274 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (Temperature) at Day 8 | 0.02 Celsius | Standard Deviation 0.278 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (Temperature) at Day 8 | 0.06 Celsius | Standard Deviation 0.3 |
Primary
Change From Baseline in Vital Sign (Temperature) at Endpoint (Week 6)
Change from baseline in vital Sign (temperature) at endpoint (Week 6) was reported.
Time frame: Baseline and Endpoint (Week 6)
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure. Endpoint (DB) values are from the last measurement within the double-blind period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign (Temperature) at Endpoint (Week 6) | 0.02 Celsius | Standard Deviation 0.317 |
| Seltorexant 10 mg | Change From Baseline in Vital Sign (Temperature) at Endpoint (Week 6) | -0.03 Celsius | Standard Deviation 0.276 |
| Seltorexant 20 mg | Change From Baseline in Vital Sign (Temperature) at Endpoint (Week 6) | -0.06 Celsius | Standard Deviation 0.242 |
| Seltorexant 40 mg | Change From Baseline in Vital Sign (Temperature) at Endpoint (Week 6) | 0.06 Celsius | Standard Deviation 0.437 |
Primary
Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition.
Time frame: Baseline to Week 6
Population: Full analysis set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -12.3 score on a scale | Standard Deviation 10.95 |
| Seltorexant 10 mg | Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -12.2 score on a scale | Standard Deviation 8.33 |
| Seltorexant 20 mg | Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -15.0 score on a scale | Standard Deviation 12.13 |
| Seltorexant 40 mg | Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -14.7 score on a scale | Standard Deviation 13.29 |
p-value: 0.72490% CI: [-3.12, 4.82]Mixed model for repeated measures (MMRM)
p-value: 0.08390% CI: [-6.13, -0.16]MMRM
p-value: 0.42490% CI: [-4.7, 1.63]MMRM
Primary
Percentage of Participants With Clinically Significant Laboratory Abnormalities
Percentage of participants with clinically significant laboratory abnormalities were reported which included Gamma-glutamyl transferase (GGT), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Albumin , bicarbonate, bilirubin, calcium, chloride, cholesterol, creatinine, direct bilirubin, glucose, high density lipoprotein (HDL) cholesterol, hemoglobin A1C, low density lipoprotein (LDL) cholesterol, phosphate, potassium, protein, sodium, triglycerides, urate, and urea nitrogen.
Time frame: Up to Week 8
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure; n (number analyzed) signifies those participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Glucose: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | HDL Cholesterol: Abnormally low | 2.3 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bicarbonate: Abnormally low | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Phosphate: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Hemoglobin A1C: Abnormally low | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Hemoglobin A1C: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Phosphate: Abnormally low | 0.7 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDL Cholesterol: Abnormally low | 4.6 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | ALT: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDL Cholesterol: Abnormally high | 7.6 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urate: Abnormally low | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDH: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bicarbonate: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urea Nitrogen: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bilirubin: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Albumin: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Triglycerides: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Calcium: Abnormally low | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Calcium: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Sodium: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Chloride: Abnormally low | 0.7 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Chloride: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | ALP: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Sodium: Abnormally low | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Cholesterol: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | CK: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Albumin: Abnormally low | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Protein:Abnormally low | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Creatinine: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urate: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Direct Bilirubin: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | AST: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Potassium: Abnormally high | 0.7 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | GGT: Abnormally high | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Glucose: Abnormally low | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Potassium: Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Potassium: Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Glucose: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urate: Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Phosphate: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Calcium: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | HDL Cholesterol: Abnormally low | 6.9 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urea Nitrogen: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Albumin: Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Glucose: Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Hemoglobin A1C: Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bicarbonate: Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Phosphate: Abnormally low | 3.2 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Chloride: Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Hemoglobin A1C: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | ALT: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urate: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Sodium: Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDL Cholesterol: Abnormally low | 10.3 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Creatinine: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDH: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Chloride: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDL Cholesterol: Abnormally high | 6.9 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | GGT: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Potassium: Abnormally high | 3.2 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | AST: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bicarbonate: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Cholesterol: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Triglycerides: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | ALP: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bilirubin: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Protein:Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Direct Bilirubin: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | CK: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Calcium: Abnormally low | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Albumin: Abnormally high | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Sodium: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDL Cholesterol: Abnormally low | 9.3 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | ALT: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Albumin: Abnormally low | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Albumin: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | ALP: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | AST: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bicarbonate: Abnormally low | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bicarbonate: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bilirubin: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Calcium: Abnormally low | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Calcium: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Chloride: Abnormally low | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Chloride: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Cholesterol: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | CK: Abnormally high | 1.7 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Creatinine: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Direct Bilirubin: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | GGT: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Glucose: Abnormally low | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Glucose: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | HDL Cholesterol: Abnormally low | 1.8 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Hemoglobin A1C: Abnormally low | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Hemoglobin A1C: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDL Cholesterol: Abnormally high | 1.9 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDH: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Phosphate: Abnormally low | 3.3 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Phosphate: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Potassium: Abnormally low | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Potassium: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Protein:Abnormally low | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Sodium: Abnormally low | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Sodium: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Triglycerides: Abnormally high | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urate: Abnormally low | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urate: Abnormally high | 5.0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urea Nitrogen: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Glucose: Abnormally low | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | GGT: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urate: Abnormally low | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Potassium: Abnormally low | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Direct Bilirubin: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Creatinine: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | ALP: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Potassium: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | CK: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Cholesterol: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Albumin: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Protein:Abnormally low | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Chloride: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Chloride: Abnormally low | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urea Nitrogen: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Sodium: Abnormally low | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Calcium: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Calcium: Abnormally low | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Urate: Abnormally high | 1.9 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Sodium: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bilirubin: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bicarbonate: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Albumin: Abnormally low | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Triglycerides: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDL Cholesterol: Abnormally high | 11.8 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDL Cholesterol: Abnormally low | 5.9 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Bicarbonate: Abnormally low | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | LDH: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Hemoglobin A1C: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Hemoglobin A1C: Abnormally low | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | AST: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Phosphate: Abnormally low | 7.8 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | HDL Cholesterol: Abnormally low | 2.0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Glucose: Abnormally high | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | ALT: Abnormally high | 1.9 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Clinically Significant Laboratory Abnormalities | Phosphate: Abnormally high | 0 percentage of participants |
Primary
Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS)
C-SSRS is a clinician-rated instrument that reports severity of both suicidal ideation and behavior. Suicidal ideation was classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods \[not plan\] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior), 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), and 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes. Minimum total score 0, maximum total score 5; higher total scores indicate more suicidal ideation and/or suicidal behavior. If no events qualify for score of 1 to 10, score of 0 was assigned (0= no event that can be assessed on the basis of C-SSRS). Higher scores indicate greater severity.
Time frame: Up to Week 8
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | No Event | 94.9 percentage of participants |
| Placebo | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal behavior | 0 percentage of participants |
| Placebo | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal ideation | 5.1 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | No Event | 96.9 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal behavior | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal ideation | 3.1 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal ideation | 3.3 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | No Event | 96.7 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal behavior | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | No Event | 94.1 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal behavior | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal ideation | 5.9 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits
Percentage of participants with treatment-emergent abnormal ECG values (Heart rate less than or equal to \[\<=\] 50 or greater than or equal to \[\>=\] 100 beats per minute \[bpm\], PR interval \<=120 or \>=200 milliseconds \[msec\], QRS interval \<=60 or \>=120 msec, and QT interval \<=200 or \>=500 msec) outside pre-defined limits were reported.
Time frame: Up to Week 6
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure; n (number analyzed) signifies those participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | Heart rate (>=100) | 0.7 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | PR interval (<=120) | 0.7 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QRS interval (>=120) | 0 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QRS interval (<=60) | 0 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QT interval (>=500) | 0 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | PR interval (>=200) | 0.7 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QT interval (<=200) | 0 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | Heart rate (<=50) | 0.7 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QT interval (>=500) | 3.3 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QRS interval (<=60) | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QRS interval (>=120) | 3.3 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | Heart rate (>=100) | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | Heart rate (<=50) | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | PR interval (<=120) | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QT interval (<=200) | 0 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | PR interval (>=200) | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QRS interval (>=120) | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QT interval (<=200) | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | Heart rate (>=100) | 1.7 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QT interval (>=500) | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | PR interval (<=120) | 0 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | Heart rate (<=50) | 3.4 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | PR interval (>=200) | 1.7 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QRS interval (<=60) | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | PR interval (>=200) | 6.0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | Heart rate (<=50) | 6.0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | Heart rate (>=100) | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | PR interval (<=120) | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QT interval (>=500) | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QRS interval (<=60) | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QRS interval (>=120) | 0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits | QT interval (<=200) | 0 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between the initial administration of study drug and 2 days after the last administration of study drug.
Time frame: Up to Week 8
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability | 40.9 percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability | 33.3 percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability | 41.0 percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability | 36.5 percentage of participants |
Primary
Physician Withdrawal Checklist-20 (PWC-20) Total Score at Day 43
Intensity of discontinuation symptoms was assessed (for example: underlying depression; anxiety-nervousness; dysphoric mood/depression; difficulty concentrating; weakness; fatigue-lethargy-lack of energy; irritability), using the Physician Withdrawal Checklist (PWC-20) administered by a trained clinician/rater. Symptoms are rated on a scale 0 (No symptom present) and 3 (severe symptoms). Total scores range from 0 to 24 calculated by adding the scores of following 8 items: Nausea-Vomiting, Diarrhea, Poor Coordination, Diaphoresis, Tremor-Tremulousness, Dizziness-Lightheadedness, Increased Acuity Sound Smell Touch, Paresthesias. Higher scores indicating more severe symptoms.
Time frame: Day 43
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Physician Withdrawal Checklist-20 (PWC-20) Total Score at Day 43 | 0.9 score on a scale | Standard Deviation 1.68 |
| Seltorexant 10 mg | Physician Withdrawal Checklist-20 (PWC-20) Total Score at Day 43 | 0.2 score on a scale | Standard Deviation 0.6 |
| Seltorexant 20 mg | Physician Withdrawal Checklist-20 (PWC-20) Total Score at Day 43 | 0.7 score on a scale | Standard Deviation 1.6 |
| Seltorexant 40 mg | Physician Withdrawal Checklist-20 (PWC-20) Total Score at Day 43 | 0.5 score on a scale | Standard Deviation 0.87 |
Primary
Physician Withdrawal Checklist-20 (PWC-20) Total Score From Day 49 to Day 56
Intensity of discontinuation symptoms was assessed (for example: underlying depression; anxiety-nervousness; dysphoric mood/depression; difficulty concentrating; weakness; fatigue-lethargy-lack of energy; irritability), using the Physician Withdrawal Checklist (PWC-20) administered by a trained clinician/rater. Symptoms are rated on a scale 0 (No symptom present) and 3 (severe symptoms). Total scores range from 0 to 24 calculated by adding the scores of following 8 items: Nausea-Vomiting, Diarrhea, Poor Coordination, Diaphoresis, Tremor-Tremulousness, Dizziness-Lightheadedness, Increased Acuity Sound Smell Touch, Paresthesias. Higher scores indicating more severe symptoms.
Time frame: Day 49 to Day 56
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Physician Withdrawal Checklist-20 (PWC-20) Total Score From Day 49 to Day 56 | 0.9 score on a scale | Standard Deviation 1.91 |
| Seltorexant 10 mg | Physician Withdrawal Checklist-20 (PWC-20) Total Score From Day 49 to Day 56 | 0.4 score on a scale | Standard Deviation 0.78 |
| Seltorexant 20 mg | Physician Withdrawal Checklist-20 (PWC-20) Total Score From Day 49 to Day 56 | 0.8 score on a scale | Standard Deviation 1.64 |
| Seltorexant 40 mg | Physician Withdrawal Checklist-20 (PWC-20) Total Score From Day 49 to Day 56 | 0.7 score on a scale | Standard Deviation 1.25 |
Secondary
Change From Baseline in Anhedonia Using the Snaith-Hamilton Pleasure Scale (SHAPS) Score at DB Endpoint (Up to Week 6)
The SHAPS is a 14-item, self-report instrument to assess hedonic capacity in adults with MDD. Each of the items has a set of 4 response categories-Definitely Agree (=1), Agree (=2), Disagree (=3), and Definitely Disagree (=4). A total score is created with either of the Disagree responses receiving a score of 1 and either of the Agree responses receiving a score of 0. The participants item responses are summed to provide a total score ranging from 0 to 14. A higher total SHAPS score indicates higher levels of current anhedonia.
Time frame: Baseline and DB Endpoint (Up to Week 6)
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Endpoint (DB) values are from the last measurement within the double-blind period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Anhedonia Using the Snaith-Hamilton Pleasure Scale (SHAPS) Score at DB Endpoint (Up to Week 6) | -3.6 Units on a scale | Standard Deviation 4.44 |
| Seltorexant 10 mg | Change From Baseline in Anhedonia Using the Snaith-Hamilton Pleasure Scale (SHAPS) Score at DB Endpoint (Up to Week 6) | -2.3 Units on a scale | Standard Deviation 4.09 |
| Seltorexant 20 mg | Change From Baseline in Anhedonia Using the Snaith-Hamilton Pleasure Scale (SHAPS) Score at DB Endpoint (Up to Week 6) | -4.2 Units on a scale | Standard Deviation 4.5 |
| Seltorexant 40 mg | Change From Baseline in Anhedonia Using the Snaith-Hamilton Pleasure Scale (SHAPS) Score at DB Endpoint (Up to Week 6) | -3.2 Units on a scale | Standard Deviation 5.2 |
Secondary
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at DB Endpoint (Up to Week 6)
The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S is a 7-point global assessment scale that measures the clinician's impression of the severity of illness exhibited by a participant, rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. Higher scores indicate worsening. Negative change in score indicates improvement.
Time frame: Baseline and DB Endpoint (Up to Week 6)
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Endpoint (DB) values are from the last measurement within the double-blind period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at DB Endpoint (Up to Week 6) | -1.0 Units on a scale |
| Seltorexant 10 mg | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at DB Endpoint (Up to Week 6) | -1.0 Units on a scale |
| Seltorexant 20 mg | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at DB Endpoint (Up to Week 6) | -1.0 Units on a scale |
| Seltorexant 40 mg | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at DB Endpoint (Up to Week 6) | -1.0 Units on a scale |
Secondary
Change From Baseline in Depressive Symptoms Using the Patient Health Questionnaire 9-Item (PHQ-9) at DB Endpoint (Up to Week 6)
The PHQ-9 is a 9-item, Patient Reported Outcome (PRO) 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 is 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 participants item responses are 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 is categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19) and Severe (20-27).
Time frame: Baseline and DB Endpoint (Up to Week 6)
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Depressive Symptoms Using the Patient Health Questionnaire 9-Item (PHQ-9) at DB Endpoint (Up to Week 6) | -7.3 Units on a scale | Standard Deviation 6.14 |
| Seltorexant 10 mg | Change From Baseline in Depressive Symptoms Using the Patient Health Questionnaire 9-Item (PHQ-9) at DB Endpoint (Up to Week 6) | -6.2 Units on a scale | Standard Deviation 5.48 |
| Seltorexant 20 mg | Change From Baseline in Depressive Symptoms Using the Patient Health Questionnaire 9-Item (PHQ-9) at DB Endpoint (Up to Week 6) | -8.6 Units on a scale | Standard Deviation 6.66 |
| Seltorexant 40 mg | Change From Baseline in Depressive Symptoms Using the Patient Health Questionnaire 9-Item (PHQ-9) at DB Endpoint (Up to Week 6) | -7.0 Units on a scale | Standard Deviation 7.64 |
Secondary
Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Total Score at Endpoint (Up to Week 6)
The EQ-5D-5L is a standardized instrument for use as a measure of health outcome, primarily designed for self-completion by respondents. It consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). EQ-5D-5L (describing and valuing health-related quality of life) descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the participant's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. Higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. EQ-VAS self-rating records respondent's own assessment of his/her overall health status at time of completion, on scale of 0 (worst health you can imagine) to 100 (best health you can imagine).
Time frame: Baseline and Endpoint (up to Week 6)
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (number of participants analyzed) signifies participants who were evaluable for this outcome measure. Endpoint (DB) values: last measurement within double-blind period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Total Score at Endpoint (Up to Week 6) | 17.4 Units on a scale | Standard Deviation 20.55 |
| Seltorexant 10 mg | Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Total Score at Endpoint (Up to Week 6) | 8.9 Units on a scale | Standard Deviation 19.34 |
| Seltorexant 20 mg | Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Total Score at Endpoint (Up to Week 6) | 23.4 Units on a scale | Standard Deviation 21.18 |
| Seltorexant 40 mg | Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Total Score at Endpoint (Up to Week 6) | 20.1 Units on a scale | Standard Deviation 23.08 |
Secondary
Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Heath State Index Total Score at DB Endpoint (Up to Week 6)
EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). The responses to 5 EQ-5D-5L dimensions were scored using a utility-weighted algorithm to derive an EQ-5D-5L health status index score between 0 (death) to 100 (full health).
Time frame: Baseline and DB Endpoint (Up to Week 6)
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (number of participants analyzed) signifies participants who were evaluable for this outcome measure. Endpoint (DB) values are from the last measurement within the double-blind period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Heath State Index Total Score at DB Endpoint (Up to Week 6) | 0.188 Units on a scale | Standard Deviation 0.2201 |
| Seltorexant 10 mg | Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Heath State Index Total Score at DB Endpoint (Up to Week 6) | 0.143 Units on a scale | Standard Deviation 0.1856 |
| Seltorexant 20 mg | Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Heath State Index Total Score at DB Endpoint (Up to Week 6) | 0.229 Units on a scale | Standard Deviation 0.2084 |
| Seltorexant 40 mg | Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Heath State Index Total Score at DB Endpoint (Up to Week 6) | 0.158 Units on a scale | Standard Deviation 0.2841 |
Secondary
Change From Baseline in Fatigue Using the Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Short Form Subscale Score at DB Endpoint (Up to Week 6)
The PROMIS-Fatigue Short Form subscale consists of a static 8 item questionnaire. It assesses a range of symptoms from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Ratings are done on a 5-item Likert scale ranging from 0 (not at all) to 5 (very much) or 0 (never) to 5(always) depending upon the question answered. Higher scores on the PROMIS-F indicate more of the concept measured (fatigue). Negative change in score indicates improvement.
Time frame: Baseline and DB Endpoint (Up to Week 6)
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Endpoint (DB) values are from the last measurement within the double-blind period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fatigue Using the Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Short Form Subscale Score at DB Endpoint (Up to Week 6) | -7.7 Units on a scale | Standard Deviation 8.45 |
| Seltorexant 10 mg | Change From Baseline in Fatigue Using the Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Short Form Subscale Score at DB Endpoint (Up to Week 6) | -7.4 Units on a scale | Standard Deviation 8.25 |
| Seltorexant 20 mg | Change From Baseline in Fatigue Using the Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Short Form Subscale Score at DB Endpoint (Up to Week 6) | -9.4 Units on a scale | Standard Deviation 8.62 |
| Seltorexant 40 mg | Change From Baseline in Fatigue Using the Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Short Form Subscale Score at DB Endpoint (Up to Week 6) | -8.0 Units on a scale | Standard Deviation 10.29 |
Secondary
Change From Baseline in ISI Total Score at DB Endpoint (Up to Week 6)
The ISI is a commonly used, 7-item psychometrically validated measure used to rate insomnia. Each item is scored 0 (no problem) to 4 (very big problem) with total between 0-28 which is calculated by adding the scores of all 7 items (absence of insomnia \[0-7\]; sub-threshold insomnia \[8-14\]; moderate insomnia \[15-21\]; and severe insomnia \[22-28\]). The change in ISI total score from baseline at DB endpoint was evaluated. Negative change in score indicates improvement.
Time frame: Baseline and DB Endpoint (Up to Week 6)
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the evaluable participants for this outcome measure. Endpoint (DB) values are from the last measurement within the double-blind period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in ISI Total Score at DB Endpoint (Up to Week 6) | -6.3 Units on a scale | Standard Deviation 6.73 |
| Seltorexant 10 mg | Change From Baseline in ISI Total Score at DB Endpoint (Up to Week 6) | -4.9 Units on a scale | Standard Deviation 6.22 |
| Seltorexant 20 mg | Change From Baseline in ISI Total Score at DB Endpoint (Up to Week 6) | -8.7 Units on a scale | Standard Deviation 6.91 |
| Seltorexant 40 mg | Change From Baseline in ISI Total Score at DB Endpoint (Up to Week 6) | -8.5 Units on a scale | Standard Deviation 8.73 |
Secondary
Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42
Exposure on the hypothalamic-pituitary-adrenal (HPA) axis in participants with MDD was evaluated by assessing change in salivary cortisol levels.
Time frame: Baseline, Days 8, 22 and 42
Population: Biomarker analysis set included all randomized participants who received at least 1 dose of study drug during the double-blind phase and had biomarker data at baseline. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure; 'n' (number analyzed) signifies those participants who were evaluable for specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 8 | 0.2 nanomoles per Liter (nmol/L) | Standard Deviation 8.41 |
| Placebo | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 42 | 1.0 nanomoles per Liter (nmol/L) | Standard Deviation 10.85 |
| Placebo | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 22 | 0.4 nanomoles per Liter (nmol/L) | Standard Deviation 8.65 |
| Seltorexant 10 mg | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 8 | 0.7 nanomoles per Liter (nmol/L) | Standard Deviation 7.24 |
| Seltorexant 10 mg | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 42 | 1.5 nanomoles per Liter (nmol/L) | Standard Deviation 6.15 |
| Seltorexant 10 mg | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 22 | 2.1 nanomoles per Liter (nmol/L) | Standard Deviation 6.39 |
| Seltorexant 20 mg | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 22 | 0.7 nanomoles per Liter (nmol/L) | Standard Deviation 6.75 |
| Seltorexant 20 mg | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 8 | 0.0 nanomoles per Liter (nmol/L) | Standard Deviation 8.64 |
| Seltorexant 20 mg | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 42 | -1.2 nanomoles per Liter (nmol/L) | Standard Deviation 6.67 |
| Seltorexant 40 mg | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 8 | -0.4 nanomoles per Liter (nmol/L) | Standard Deviation 6.19 |
| Seltorexant 40 mg | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 42 | -0.5 nanomoles per Liter (nmol/L) | Standard Deviation 6.69 |
| Seltorexant 40 mg | Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42 | Change at Day 22 | 1.0 nanomoles per Liter (nmol/L) | Standard Deviation 10.75 |
Secondary
Change From Baseline in Severity of Depression Using the Patient Global Impression-Severity (PGI-S) Score at DB Endpoint (Up to Week 6)
The PGI-S is a self-report scale to measure severity of illness (1=none, 2=mild, 3=moderate, 4=severe). Higher score indicates more illness severity. Negative change in score indicates improvement.
Time frame: Baseline and DB Endpoint (Up to Week 6)
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Endpoint (DB) values are from the last measurement within the double-blind period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Severity of Depression Using the Patient Global Impression-Severity (PGI-S) Score at DB Endpoint (Up to Week 6) | -1.0 Units on a scale |
| Seltorexant 10 mg | Change From Baseline in Severity of Depression Using the Patient Global Impression-Severity (PGI-S) Score at DB Endpoint (Up to Week 6) | 0.0 Units on a scale |
| Seltorexant 20 mg | Change From Baseline in Severity of Depression Using the Patient Global Impression-Severity (PGI-S) Score at DB Endpoint (Up to Week 6) | -1.0 Units on a scale |
| Seltorexant 40 mg | Change From Baseline in Severity of Depression Using the Patient Global Impression-Severity (PGI-S) Score at DB Endpoint (Up to Week 6) | -1.0 Units on a scale |
Secondary
Change From Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form at DB Endpoint (Up to Week 6)
The PROMIS-SD Short Form subscale consists of a static 8 item questionnaire. It assesses the concepts of sleep initiation (2 items), quality of sleep (3 items), early morning feelings (2 items) and worrying about sleep (1 item). Responses to each of the 8 items range from 1 to 5, and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS-SD indicate more of the concept measured (disturbed sleep). Negative change in score indicates improvement.
Time frame: Baseline and DB Endpoint (Up to Week 6)
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form at DB Endpoint (Up to Week 6) | -6.4 Units on a scale | Standard Deviation 8.53 |
| Seltorexant 10 mg | Change From Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form at DB Endpoint (Up to Week 6) | -5.1 Units on a scale | Standard Deviation 8.39 |
| Seltorexant 20 mg | Change From Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form at DB Endpoint (Up to Week 6) | -10.2 Units on a scale | Standard Deviation 9.21 |
| Seltorexant 40 mg | Change From Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form at DB Endpoint (Up to Week 6) | -10.9 Units on a scale | Standard Deviation 9.25 |
Secondary
Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Day 42
HAM-A is a 14-item scale designed to measure anxiety in individuals. Each question reflects a symptom of anxiety and physical as well as mental symptoms are represented. Each of the 14-items in the scale is scored on a 5-point scale, ranging from 0 (a complete lack of that symptom) to 4 (a very severe show of anxiety with that symptom). The total score ranges from 0 to 56 which is calculated by adding the scores of all 14 items, where 0-13 indicates normal range, 14-17 indicates mild severity, 18 -24: mild to moderate severity, 25 -30: moderate to severe, and \>=31: severe. Higher score indicates worsening. Negative change in score indicates improvement.
Time frame: Baseline and Day 42
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the evaluable participants for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Day 42 | -8.7 Units on a scale | Standard Deviation 7.92 |
| Seltorexant 10 mg | Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Day 42 | -9.9 Units on a scale | Standard Deviation 5.57 |
| Seltorexant 20 mg | Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Day 42 | -9.6 Units on a scale | Standard Deviation 9.31 |
| Seltorexant 40 mg | Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Day 42 | -9.9 Units on a scale | Standard Deviation 10.17 |
Secondary
Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress
MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. Negative change in score indicates improvement.
Time frame: Baseline and Day 42
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure; 'n' (number analyzed) signifies those participants who were evaluable for specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress | MDD with Anxious Distress | -13.9 Units on a scale | Standard Deviation 11.5 |
| Placebo | Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress | MDD without Anxious distress | -9.7 Units on a scale | Standard Deviation 9.59 |
| Seltorexant 10 mg | Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress | MDD without Anxious distress | -13.4 Units on a scale | Standard Deviation 8.15 |
| Seltorexant 10 mg | Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress | MDD with Anxious Distress | -11.0 Units on a scale | Standard Deviation 8.67 |
| Seltorexant 20 mg | Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress | MDD with Anxious Distress | -16.9 Units on a scale | Standard Deviation 12.31 |
| Seltorexant 20 mg | Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress | MDD without Anxious distress | -12.5 Units on a scale | Standard Deviation 11.7 |
| Seltorexant 40 mg | Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress | MDD with Anxious Distress | -15.3 Units on a scale | Standard Deviation 13 |
| Seltorexant 40 mg | Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress | MDD without Anxious distress | -13.8 Units on a scale | Standard Deviation 14.63 |
Secondary
Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42
MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. The ISI has 7 questions, each rated on a 5-point Likert scale ranging from 0 to 4. The total score is calculated as the sum of the 7 items ranging from 0 to 28. Higher scores represent a more severe condition.
Time frame: Baseline and Day 42
Population: Full analysis set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, N (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure; 'n' (number analyzed) signifies those participants who were evaluable for specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42 | Day 42: Baseline ISI score per IWRS less than (<)15 | -13.3 score on a scale | Standard Deviation 10.83 |
| Placebo | Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42 | Day 42: Baseline ISI score per IWRS>=15 | -11.6 score on a scale | Standard Deviation 11.06 |
| Seltorexant 10 mg | Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42 | Day 42: Baseline ISI score per IWRS>=15 | -10.4 score on a scale | Standard Deviation 10.41 |
| Seltorexant 10 mg | Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42 | Day 42: Baseline ISI score per IWRS less than (<)15 | -12.6 score on a scale | Standard Deviation 8.01 |
| Seltorexant 20 mg | Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42 | Day 42: Baseline ISI score per IWRS less than (<)15 | -13.0 score on a scale | Standard Deviation 11.38 |
| Seltorexant 20 mg | Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42 | Day 42: Baseline ISI score per IWRS>=15 | -16.5 score on a scale | Standard Deviation 12.62 |
| Seltorexant 40 mg | Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42 | Day 42: Baseline ISI score per IWRS less than (<)15 | -14.9 score on a scale | Standard Deviation 12.14 |
| Seltorexant 40 mg | Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42 | Day 42: Baseline ISI score per IWRS>=15 | -14.6 score on a scale | Standard Deviation 13.87 |
Secondary
Change From Baseline in the Sheehan Disability Scale (SDS) Score at Day 42
The SDS is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. The first 3 items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0-10 rating scale. The scores for the first 3 items are summed to create a total score of 0-30, where a higher score indicates greater impairment. It also has 1 item on days lost from school or work and 1 item on days when underproductive. Negative change in score indicates improvement.
Time frame: Baseline and Day 42
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Sheehan Disability Scale (SDS) Score at Day 42 | -7.9 Units on a scale | Standard Deviation 6.99 |
| Seltorexant 10 mg | Change From Baseline in the Sheehan Disability Scale (SDS) Score at Day 42 | -7.5 Units on a scale | Standard Deviation 5.19 |
| Seltorexant 20 mg | Change From Baseline in the Sheehan Disability Scale (SDS) Score at Day 42 | -7.9 Units on a scale | Standard Deviation 7.46 |
| Seltorexant 40 mg | Change From Baseline in the Sheehan Disability Scale (SDS) Score at Day 42 | -5.9 Units on a scale | Standard Deviation 9.2 |
Secondary
Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6)
The WLQ is to assess the on-the-job impact of chronic health problems and/or treatment (work limitations) in adults. It is a 8-item questionnaire self-report rating scale developed to measure the on-the-job impact of chronic health problems and/or treatment (work limitations). It comprises five dimensions of limitations: handling time, physical, mental-interpersonal, productivity loss and output demands. Participants respond to each item with options ranging from 'Almost all of the time' to 'none of the time', or 'Does not apply to my job'. Each dimension of limitations have a scale score ranging from 0 to 100 with lower score indicating low level of work limitations.
Time frame: Baseline and DB Endpoint (Up to Week 6)
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure; 'n' (number analyzed) signifies those participants who were evaluable for specific categories. Endpoint (DB) values are from the last measurement within the double-blind period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Output demand scale | -23.9 Units on a scale | Standard Deviation 26.72 |
| Placebo | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Physical demands | -15.2 Units on a scale | Standard Deviation 23.64 |
| Placebo | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Productivity loss | -5.1 Units on a scale | Standard Deviation 5.56 |
| Placebo | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Mental interpersonal scale | -21.2 Units on a scale | Standard Deviation 27.61 |
| Placebo | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Time management | -21.3 Units on a scale | Standard Deviation 30.41 |
| Seltorexant 10 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Mental interpersonal scale | -19.5 Units on a scale | Standard Deviation 25.28 |
| Seltorexant 10 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Output demand scale | -22.2 Units on a scale | Standard Deviation 27.8 |
| Seltorexant 10 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Productivity loss | -4.7 Units on a scale | Standard Deviation 5.3 |
| Seltorexant 10 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Physical demands | -23.5 Units on a scale | Standard Deviation 26.1 |
| Seltorexant 10 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Time management | -18.2 Units on a scale | Standard Deviation 28.28 |
| Seltorexant 20 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Mental interpersonal scale | -26.28 Units on a scale | Standard Deviation 27.89 |
| Seltorexant 20 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Time management | -21.8 Units on a scale | Standard Deviation 34.46 |
| Seltorexant 20 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Physical demands | -11.7 Units on a scale | Standard Deviation 31.4 |
| Seltorexant 20 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Output demand scale | -20.3 Units on a scale | Standard Deviation 30.08 |
| Seltorexant 20 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Productivity loss | -4.7 Units on a scale | Standard Deviation 6.16 |
| Seltorexant 40 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Output demand scale | -21.7 Units on a scale | Standard Deviation 35.8 |
| Seltorexant 40 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Physical demands | -14.3 Units on a scale | Standard Deviation 35.37 |
| Seltorexant 40 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Time management | -20.8 Units on a scale | Standard Deviation 37.48 |
| Seltorexant 40 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Mental interpersonal scale | -15.9 Units on a scale | Standard Deviation 31.76 |
| Seltorexant 40 mg | Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6) | Productivity loss | -4.6 Units on a scale | Standard Deviation 7.02 |
Secondary
Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score
Participants with a MADRS total score of less than or equal to (\<=) 8, \<=10, and \<=12 at a given time point were considered as remitters. MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. Participants with missing values at a given time point were imputed as non-responders.
Time frame: Day 42
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=12) | 19.0 Percentage of participants |
| Placebo | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=8) | 16.1 Percentage of participants |
| Placebo | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=10) | 17.5 Percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=12) | 15.2 Percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=8) | 6.1 Percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=10) | 9.1 Percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=10) | 26.2 Percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=12) | 29.5 Percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=8) | 23.0 Percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=12) | 26.9 Percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=8) | 19.2 Percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score | MADRS (<=10) | 26.9 Percentage of participants |
Secondary
Percentage of Participants With Response on Anxiety Symptoms Scale Based on HAM-A Total Score
Participants with a \>=50 percent improvement in the HAM-A total score from baseline at a given timepoint were considered as responders. HAM-A is a 14-item scale designed to measure anxiety in individuals. Each question reflects a symptom of anxiety and physical as well as mental symptoms are represented. Each of the 14-items in the scale is scored on a 5-point scale, ranging from 0 (a complete lack of that symptom) to 4 (a very severe show of anxiety with that symptom). The total score ranges from 0 to 56 which is calculated by adding the scores of all 14 items, where 0-13 indicates normal range, 14-17 indicates mild severity, 18 -24: mild to moderate severity, 25 -30: moderate to severe, and \>=31: severe. Higher score indicates worsening. Participants with missing values at a given time point were imputed as non-responders.
Time frame: Day 42
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Response on Anxiety Symptoms Scale Based on HAM-A Total Score | 37.2 Percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Response on Anxiety Symptoms Scale Based on HAM-A Total Score | 57.6 Percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Response on Anxiety Symptoms Scale Based on HAM-A Total Score | 50.8 Percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Response on Anxiety Symptoms Scale Based on HAM-A Total Score | 46.2 Percentage of participants |
Secondary
Percentage of Participants With Response on Depressive Symptoms Scale Based on MADRS Total Score
Responders are defined as participants with a \>=50 percent (%) improvement in the MADRS total score from baseline to a given timepoint. MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. Participants with missing values at a given time point were imputed as non-responders.
Time frame: Day 42
Population: Full analysis set included participants who were randomly assigned to study drug and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Response on Depressive Symptoms Scale Based on MADRS Total Score | 28.5 Percentage of participants |
| Seltorexant 10 mg | Percentage of Participants With Response on Depressive Symptoms Scale Based on MADRS Total Score | 24.2 Percentage of participants |
| Seltorexant 20 mg | Percentage of Participants With Response on Depressive Symptoms Scale Based on MADRS Total Score | 41.0 Percentage of participants |
| Seltorexant 40 mg | Percentage of Participants With Response on Depressive Symptoms Scale Based on MADRS Total Score | 38.5 Percentage of participants |
Secondary
Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16)
Plasma concentrations of Seltorexant and its metabolites (M12 and M16) over time were reported.
Time frame: Day 1: Between 0.25 hours (h) to 1.5 hour, 2 to 4 hours, and 6 to 8 hours post-dose; Day 8 (morning): 6 to 12 hours post evening dose of Day 7
Population: Safety analyses set included all participants who were randomly assigned to study drug and received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure; 'n' (number analyzed) signifies those participants who were evaluable for specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 1, 0.25h-1.5h | 181 nanograms per milliliter (ng/mL) | Standard Deviation 165 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 1, 2-4h | 199 nanograms per milliliter (ng/mL) | Standard Deviation 113 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 1, 6-8h | 117 nanograms per milliliter (ng/mL) | Standard Deviation 99.3 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 8, Morning (6 to 12 hours post evening dose of Day 7) | 52.8 nanograms per milliliter (ng/mL) | Standard Deviation 65.8 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 1,0.25h-1.5h | 118 nanograms per milliliter (ng/mL) | Standard Deviation 107 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 1, 2-4h | 146 nanograms per milliliter (ng/mL) | Standard Deviation 58.8 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 1, 6-8h | 105 nanograms per milliliter (ng/mL) | Standard Deviation 73.5 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 8, Morning (6 to 12 hours post evening dose of Day 7) | 76.2 nanograms per milliliter (ng/mL) | Standard Deviation 79 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 1, 0.25h-1.5h | 29.1 nanograms per milliliter (ng/mL) | Standard Deviation 30.2 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 1, 2-4h | 33.3 nanograms per milliliter (ng/mL) | Standard Deviation 15.7 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 1, 6-8h | 27.5 nanograms per milliliter (ng/mL) | Standard Deviation 16.6 |
| Placebo | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 8, Morning (6 to 12 hours post evening dose of Day 7) | 23.7 nanograms per milliliter (ng/mL) | Standard Deviation 14.9 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 8, Morning (6 to 12 hours post evening dose of Day 7) | 37.6 nanograms per milliliter (ng/mL) | Standard Deviation 36.1 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 1, 0.25h-1.5h | 277 nanograms per milliliter (ng/mL) | Standard Deviation 291 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 1, 6-8h | 187 nanograms per milliliter (ng/mL) | Standard Deviation 189 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 1, 0.25h-1.5h | 47 nanograms per milliliter (ng/mL) | Standard Deviation 53.4 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 1, 2-4h | 374 nanograms per milliliter (ng/mL) | Standard Deviation 232 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 1, 2-4h | 283 nanograms per milliliter (ng/mL) | Standard Deviation 185 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 1, 6-8h | 40.1 nanograms per milliliter (ng/mL) | Standard Deviation 31.4 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 1, 6-8h | 167 nanograms per milliliter (ng/mL) | Standard Deviation 179 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 8, Morning (6 to 12 hours post evening dose of Day 7) | 99 nanograms per milliliter (ng/mL) | Standard Deviation 133 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 1,0.25h-1.5h | 194 nanograms per milliliter (ng/mL) | Standard Deviation 223 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 8, Morning (6 to 12 hours post evening dose of Day 7) | 69.4 nanograms per milliliter (ng/mL) | Standard Deviation 119 |
| Seltorexant 10 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 1, 2-4h | 61.4 nanograms per milliliter (ng/mL) | Standard Deviation 35.7 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 8, Morning (6 to 12 hours post evening dose of Day 7) | 104 nanograms per milliliter (ng/mL) | Standard Deviation 203 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 1,0.25h-1.5h | 357 nanograms per milliliter (ng/mL) | Standard Deviation 367 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 1, 2-4h | 101 nanograms per milliliter (ng/mL) | Standard Deviation 49.3 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 1, 2-4h | 513 nanograms per milliliter (ng/mL) | Standard Deviation 284 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 1, 6-8h | 279 nanograms per milliliter (ng/mL) | Standard Deviation 278 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M12: Day 8, Morning (6 to 12 hours post evening dose of Day 7) | 169 nanograms per milliliter (ng/mL) | Standard Deviation 251 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 1, 6-8h | 70.6 nanograms per milliliter (ng/mL) | Standard Deviation 33.6 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 1, 0.25h-1.5h | 535 nanograms per milliliter (ng/mL) | Standard Deviation 500 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 1, 2-4h | 647 nanograms per milliliter (ng/mL) | Standard Deviation 325 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 1, 0.25h-1.5h | 71.4 nanograms per milliliter (ng/mL) | Standard Deviation 78.3 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | Seltorexant: Day 1, 6-8h | 207 nanograms per milliliter (ng/mL) | Standard Deviation 169 |
| Seltorexant 20 mg | Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16) | M16: Day 8, Morning (6 to 12 hours post evening dose of Day 7) | 61.7 nanograms per milliliter (ng/mL) | Standard Deviation 43.7 |