Phase 3 Study of Adjunctive Treatment With Seltorexant in Adult and Elderly Participants With Major Depressive Disorder and Insomnia Symptoms

Inclusion Criteria:

Participants in part 1 and direct enrollers to part 2:

• Meet DSM-5 MDD, without psychotic features based upon clinical assessment andconfirmed by the structured clinical interview for DSM-5 Axis I disorders-clinicaltrials version (SCID-CT) diagnosed with first depressive episode prior to age 60

• Have had an inadequate response to at least 1 but no more than 2 antidepressants,administered at an adequate dose and duration in the current episode of depression.An inadequate response is defined as less than (<) 50% reduction but with someimprovement (that is, improvement greater than [>] 0%) in depressive symptomseverity with residual symptoms other than insomnia present, and overall goodtolerability, as assessed by the MGH-ATRQ, and this must include the participant'scurrent antidepressant treatment

• Is receiving and tolerating well any one of the following SSRI or SNRI fordepressive symptoms at screening, in any formulation and available in theparticipating country: citalopram, duloxetine, escitalopram, fluvoxamine,fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine,desvenlafaxine, vilazodone, or vortioxetine at a stable dose (at therapeutic doselevel) for at least 6 weeks

• Having a major depressive episode of at least moderate severity, as assessed with 17-item Hamilton Depression Rating Scale, implemented through the StructuredInterview Guide (SIGH-D) in a blinded manner at screening and must not demonstrate aclinically significant improvement from the beginning to end of screening.

Participants entering after completing part 1:

• Must have completed Part 1 DB treatment phase

• Can consistently tolerate study drug (at the end of Part 1), and there is noadditional safety risk for the participant if they proceed to Part 2

• Was able to consistently follow the study procedures in Part 1 as judged by theinvestigator.

• Must be medically stable based on clinical laboratory tests

Exclusion Criteria:

• Has a recent (last 3 months) history of, or current signs and symptoms of, severerenal insufficiency clinically significant or unstable cardiovascular, respiratory,gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrinedisorders and uncontrolled Type 1 or Type 2 diabetes mellitus

• Has a history of narcolepsy and seizures

• Has current signs/symptoms of hypothyroidism or hyperthyroidism

• Participants taking thyroid supplementation for antidepressant purposes

• Has Cushing's disease, Addison's disease, primary amenorrhea, or other evidence ofsignificant medical disorders of the HPA axis