Seltorexant Dose 1

The MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.

An AE is any untoward medical occurrence in a clinical study participant administered with a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. The following AESIs are considered in this study: Suicidal thoughts, suicidal ideation, and suicidal behavior; Cataplexy; Sleep paralysis; Complex, sleep-related behaviors/parasomnias; Fall and Motor vehicle accident.

Number of participants with vital signs (blood pressure and pulse/heart rate measurements) abnormalities will be reported.

The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed to assess severity and track suicidal events through any treatment. The C-SSRS scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 'yes/no' items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent.

Potential withdrawal effects will be assessed by the PWC-20. The PWC-20 is a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 is a reliable and sensitive instrument for the assessment of discontinuation symptoms.

Number of participants with abnormalities in ECG will be reported.

The ASEX is a patient-reported 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction. The scale has shown satisfactory reliability and validity.

Change from baseline in body weight will be reported.

Change from baseline in BMI will be reported.

Change from baseline in waist circumference will be reported.

Number of participants with laboratory abnormalities related to hematology, serum chemistry will be reported.

The MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.

Stable response is defined as a greater than equal to (\>=) 50 percent (%) reduction in the MADRS total score for the last 3 consecutive visits of the OL stabilization Phase, as assessed by the site investigator. Time from randomization to the first relapse during the DB maintenance phase in participants who achieve a stable response at the end of OL seltorexant treatment will be reported.

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

An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study drug. Treatment emergent AEs was defined as any AE occurred at or after the initial administration of study intervention through the day of last dose plus 2 days.

AE was defined as any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study drug. Treatment emergent AEs was defined as any AE occurred at or after the initial administration of study intervention through the day of last dose plus 2 days. The AEs considered to be of special interest: cataplexy, sleep paralysis, complex, sleep-related behaviors/parasomnias such as confusional arousals, somnambulism, sleep terrors, bruxism, sleep sex, sleep-related eating disorder, and catathrenia, fall, motor vehicle accident.

Change from baseline in vital signs: systolic/diastolic blood pressure were reported. Blood pressure measurements were assessed with the participant in a sitting position using a completely automated device.

Change from baseline in BMI were reported.

Change from baseline in vital signs: temperature were reported.

Change from baseline in vital signs: pulse rate were reported. Pulse rate measurements were assessed with the participant in a sitting position using a completely automated device.

Change from baseline in weight was reported.

Change from baseline in waist circumference were reported.

C-SSRS is a clinician-rated instrument that reports severity and frequency of suicide-related ideation and behaviors. Suicidal ideation was classified on a 5-item scale: 1 (wish to be dead), 2 (non-specific active suicidal thoughts), 3 (suicidal ideation without plan and intent), 4 (suicidal ideation intent to act without plan), and 5 (suicidal ideation with plan and intent), Suicidal behavior is classified on a 5-item scale: 6 (preparatory acts or behavior), 7 (aborted attempt), 8 (interrupted attempt), 9 (actual attempt), and 10 (suicide). Total score from 10 categories was summarized into 3 categories: No suicidal ideation or behavior(0), suicidal ideation (1-5), suicidal behavior (6-10). Total score ranged from 0 to 10, higher total scores indicate more suicidal ideation and/or suicidal behavior. Categories with at least 1 non-zero data values are reported.

The PWC-20 was a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 was a reliable and sensitive instrument for the assessment of discontinuation symptoms. The assessment has 20 items (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue, poor coordination, restlessness, diaphoresis, tremor, dizziness, headaches, muscle aches or stiffness, weakness, increased acuity sound smell touch, paresthesia, difficulty concentrating-remember, depersonalization-derealization) evaluated to detect withdrawal symptoms. Symptoms are rated on a scale: 0-3, 0 =not present, 1=mild, 2 =moderate, and 3 =severe. The total PWC-20 score was the sum of 20 item scores and ranged from 0 to 60. The higher score indicates more severe symptoms.

The PWC-20 was a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 was a reliable and sensitive instrument for the assessment of discontinuation symptoms. The assessment has 20 items (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue, poor coordination, restlessness, diaphoresis, tremor, dizziness, headaches, muscle aches or stiffness, weakness, increased acuity sound smell touch, paresthesia, difficulty concentrating-remember, depersonalization-derealization) evaluated to detect withdrawal symptoms. Symptoms are rated on a scale: 0-3, 0 =not present, 1=mild, 2 =moderate, and 3 =severe. The total PWC-20 score was the sum of 20 item scores and ranged from 0 to 60. The higher score indicates more severe symptoms.

The PWC-20 was a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 was a reliable and sensitive instrument for the assessment of discontinuation symptoms. The assessment has 20 items (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue, poor coordination, restlessness, diaphoresis, tremor, dizziness, headaches, muscle aches or stiffness, weakness, increased acuity sound smell touch, paresthesia, difficulty concentrating-remember, depersonalization-derealization)evaluated to detect withdrawal symptoms. Symptoms are rated on a scale: 0-3, 0 =not present, 1=mild, 2 =moderate, and 3 =severe. The total PWC-20 score was the sum of 20 item scores and ranged from 0 to 60. The higher score indicates more severe symptoms.

Number of participants with ECG abnormalities during OL treatment phase was reported. ECG abnormalities were assessed as per investigator's discretion.

Laboratory parameters: hematology (platelet count, red blood cell \[RBC\] count, hemoglobin, hematocrit, neutrophils (Segmented/Leukocytes), lymphocytes, monocytes, eosinophils/leukocytes \[Eos/Leu\], basophils, Reticulocytes/ Erythrocytes \[Reti/Ery\]); chemistry (sodium, potassium, chloride, bicarbonate, creatinine, Creatine Kinase, glucose, aspartate transaminase \[AST\], alanine transaminase \[ALT\], gamma-glutamyl transferase \[GGT\], alkaline phosphatase, total bilirubin, phosphate, albumin, total protein, total cholesterol, high-density lipoprotein, low-density lipoprotein, Triglycerides); urine (specific gravity, pH, glucose, blood, bilirubin, urobilinogen, RBC). Clinically significant abnormalities (low/high) were determined at the investigator's discretion. Only those categories in which at least one participant had data were reported in this outcome measure.

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 Likert 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. Sexual dysfunction is defined as an ASEX total score of 19 or greater, or a score of 5 or greater on any item, or a score of 4 or greater on any 3 items.

Responders are defined as percentage of participants with greater than or equal to (\>=) 50 percent (%) improvement in the montgomery-asberg depression rating scale (MADRS) total score from baseline. 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 of 60. Higher scores represent a more severe condition.

In the participants with major depressive disorder (MDD), driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test to evaluate the effect of seltorexant dose 1, compared to placebo, as an add-on medication to an antidepressant.