A Study of Oral Seltorexant as an add-on Medication to an Antidepressant on On-road Driving Performance in Participants With Major Depressive Disorder

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effect of seltorexant, compared to placebo, as an add-on medication to an antidepressant, on next-day driving performance as assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test in participants with major depressive disorder (MDD).

Official Title
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A Multicentric, Randomized, Double-Blind, Placebo- and Positive-Controlled 4-way Crossover Study to Evaluate the Effects of Single and Repeated Administration of Oral Seltorexant as an add-on Medication to an Antidepressant on On-Road Driving Performance in Participants With Major Depressive Disorder

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Drug: Seltorexant Dose 1
* Drug: Seltorexant Dose 2
* Drug: Placebo
* Drug: Zopiclone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant with major depressive disorder (MDD) (not applicable for elderly without MDD) must 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 (DSM-5 296.20, 296.21, 296.25, 296.26, 296.30, 296.31, 296.35 or 296.36) and confirmed by the Mini International Neuropsychiatric Interview (MINI) and the attending general physician, psychiatrist or mental health practitioner. The MINI will also be conducted for elderly participants without MDD to rule out major psychiatric disorders Participants with MDD (not applicable for elderly without MDD) must have mild or better depressive symptoms indicated by a Montgomery-Asberg Depression Rating Scale (MADRS) total score of less than or equal to (<=) 18 at screening Participants with MDD having comorbid generalized anxiety disorder, social anxiety disorder, or panic disorder for whom major depressive disorder (MDD) is considered the primary diagnosis are not excluded Participants with MDD (not applicable for elderly without MDD) must be receiving and tolerating well any one of the following selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) for depressive symptoms in any formulation and available in the participating country: citalopram, duloxetine, escitalopram, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable dose (at therapeutic dose level) for at least 4 weeks prior to screening, and expected to continue to take the same drug and dose for the duration of the study Participant should be medically stable on the basis of medical history, neurological examination and clinical laboratory tests performed at screening, and physical examination, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and predose on Day 1 of Period 1. Exclusion Criteria: Participants has a recent (last 3 months) history of, or current signs and symptoms of severe renal insufficiency (creatinine clearance less than [<]30 milliliter per minute [mL/min]); clinically significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrine disorders; and participants with uncontrolled type 1 or type 2 diabetes mellitus Participants has clinically significant hepatic disease as defined by greater than or equal to (>=) 2* Upper Limit of Normal [ULN]) increase of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at screening (one retest is permitted); and significant liver disease including cirrhosis, ascites, active hepatitis etc. (fatty liver disease or Gilbert's syndrome will be allowed as long as it does not meet the above criteria) Participants has current signs/symptoms of hypothyroidism or hyperthyroidism. For participants with a history of thyroid disease and for participants who, regardless of thyroid history have the thyroid stimulating hormone (TSH) value out of range, a free thyroxine (FT4) test will be conducted. If the FT4 value is abnormal and considered to be clinically significant (after discussion with the medical monitor) the participant is not eligible. Participants with a pre-existing history of thyroid disease/disorder who are treated with thyroid hormones need to be on a stable dosage for 3 months prior to the start of the screening phase. Participants taking thyroid supplementation for antidepressant purposes are not allowed in the study Participants has Cushing's Disease, Addison's Disease, primary amenorrhea, or other evidence of significant medical disorders of the hypothalamic-pituitary-adrenal (HPA) axis Participants has a lifetime history of narcolepsy and seizures (except childhood seizures)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence CADB<br>Participants will receive placebo once daily (OD) at bedtime for 8 consecutive days from Day 1 to Day 8 (Treatment C) in Period 1 followed by Dose 1 of seltorexant tablets and placebo OD at bedtime for 8 consecutive days from Day 1 to Day 8 (Treatment A) in Period 2 followed by Dose 2 of seltorexant tablets OD at bedtime for 8 consecutive days from Day 1 to Day 8 (Treatment D) in Period 3 followed by zopiclone on Day 1 and Day 8 and placebo from Day 2 to Day 7 OD at bedtime (Treatment B) in Period 4. There will be a washout period of 5 to 21 days between each period. | Drug: Seltorexant Dose 1<br>* Participants will receive Dose 1 of seltorexant OD from Day 1 to Day 8 as part of Treatment A as per assigned treatment sequence.<br>* Other names: JNJ-42847922;Drug: Seltorexant Dose 2<br>* Participants will receive Dose 2 of seltorexant OD from Day 1 to Day 8 as part of Treatment D as per assigned treatment sequence.<br>* Other names: JNJ-42847922;Drug: Placebo<br>* Participants will receive placebo of seltorexant OD from Day 1 to Day 8 as a part of Treatment A and C and from Day 2 and Day 7 as a part of Treatment B as per assigned treatment sequence.<br>Drug: Zopiclone<br>* Participants will receive Dose 3 of zopiclone OD from Day 1 to Day 8 as a part of Treatment B as per assigned treatment sequence.<br>|
| Experimental: Treatment Sequence ABCD<br>Participants will receive Treatment A in Period 1 followed by Treatment B in Period 2 followed by Treatment C in Period 3 followed by Treatment D in Period 4. There will be a washout period of 5 to 21 days between each period. | Drug: Seltorexant Dose 1<br>* Participants will receive Dose 1 of seltorexant OD from Day 1 to Day 8 as part of Treatment A as per assigned treatment sequence.<br>* Other names: JNJ-42847922;Drug: Seltorexant Dose 2<br>* Participants will receive Dose 2 of seltorexant OD from Day 1 to Day 8 as part of Treatment D as per assigned treatment sequence.<br>* Other names: JNJ-42847922;Drug: Placebo<br>* Participants will receive placebo of seltorexant OD from Day 1 to Day 8 as a part of Treatment A and C and from Day 2 and Day 7 as a part of Treatment B as per assigned treatment sequence.<br>Drug: Zopiclone<br>* Participants will receive Dose 3 of zopiclone OD from Day 1 to Day 8 as a part of Treatment B as per assigned treatment sequence.<br>|
| Experimental: Treatment Sequence BDAC<br>Participants will receive Treatment B in Period 1 followed by Treatment D in Period 2 followed by Treatment A in Period 3 followed by Treatment C in Period 4. There will be a washout period of 5 to 21 days between each period. | Drug: Seltorexant Dose 1<br>* Participants will receive Dose 1 of seltorexant OD from Day 1 to Day 8 as part of Treatment A as per assigned treatment sequence.<br>* Other names: JNJ-42847922;Drug: Seltorexant Dose 2<br>* Participants will receive Dose 2 of seltorexant OD from Day 1 to Day 8 as part of Treatment D as per assigned treatment sequence.<br>* Other names: JNJ-42847922;Drug: Placebo<br>* Participants will receive placebo of seltorexant OD from Day 1 to Day 8 as a part of Treatment A and C and from Day 2 and Day 7 as a part of Treatment B as per assigned treatment sequence.<br>Drug: Zopiclone<br>* Participants will receive Dose 3 of zopiclone OD from Day 1 to Day 8 as a part of Treatment B as per assigned treatment sequence.<br>|
| Experimental: Treatment Sequence DCBA<br>Participants will receive Treatment D in Period 1 followed by Treatment C in Period 2 followed by Treatment B in Period 3 followed by Treatment A in Period 4. There will be a washout period of 5 to 21 days between each period. | Drug: Seltorexant Dose 1<br>* Participants will receive Dose 1 of seltorexant OD from Day 1 to Day 8 as part of Treatment A as per assigned treatment sequence.<br>* Other names: JNJ-42847922;Drug: Seltorexant Dose 2<br>* Participants will receive Dose 2 of seltorexant OD from Day 1 to Day 8 as part of Treatment D as per assigned treatment sequence.<br>* Other names: JNJ-42847922;Drug: Placebo<br>* Participants will receive placebo of seltorexant OD from Day 1 to Day 8 as a part of Treatment A and C and from Day 2 and Day 7 as a part of Treatment B as per assigned treatment sequence.<br>Drug: Zopiclone<br>* Participants will receive Dose 3 of zopiclone OD from Day 1 to Day 8 as a part of Treatment B as per assigned treatment sequence.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Driving Performance as Assessed by the Mean Difference of SDLP From an on-road Driving Test | 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. | Day 2 | 
| Driving Performance as Assessed by the Mean Difference of SDLP From an on-road Driving Test | In the participants with MDD, driving performance will be assessed by the mean difference of 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. | Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Driving Performance as Assessed by the Mean Difference of SDLP From an on-road Driving Test | The driving performance will be assessed by the mean difference of SDLP from an on-road driving test to evaluate the effect of seltorexant doses (Dose 1 and Dose 2), compared to placebo in adult participants with major depressive disorder (MDD); and on adults and elderly participants with MDD and healthy elderly (if enrolled) (seltorexant Dose 1 and Dose 2); and on adults and elderly participants with MDD (seltorexant Dose 2). | Day 2 and Day 9 | 
| Participant Driving Performance as Assessed by Visual Analog Scale | Immediately after each driving test, participants with MDD or in healthy elderly participants (if enrolled) will indicate the perceived quality of their driving performance on a visual analog scale from 0 ('I drove exceptionally poorly') to 20 ('I drove exceptionally well') around a midpoint of 'I drove normally'. | Day 2 and Day 9 | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | An adverse event is any untoward medical occurrence in a clinical study participant with MDD or in healthy elderly participants (if enrolled) administered a medicinal (investigational or non investigational) product. An adverse event does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product. | Up to 20 weeks |