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

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 3

Conditions: Depressive Disorder, Major

Treatments: Drug: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI); Drug: Placebo; Drug: Seltorexant

Study type: Interventional

Funder types: Industry

Identifiers

NCT06559306

42847922MDD3003

2023-509070-36-00 (Registry Identifier)

Details and patient eligibility

About

The purpose of this study is to know how well seltorexant works, and also to evaluate safety and maintenance effect of seltorexant compared with placebo as an adjunctive therapy to an antidepressant in improving depressive symptoms in participants with major depressive disorder with insomnia symptoms (MDDIS) who have had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).

Enrollment: 752 estimated patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants in part 1 and direct enrollers to part 2:

• Meet DSM-5 MDD, without psychotic features based upon clinical assessment and confirmed by the structured clinical interview for DSM-5 Axis I disorders-clinical trials version (SCID-CT) diagnosed with first depressive episode prior to age 60
• 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 some improvement (that is, improvement greater than [>] 0%) in depressive symptom severity with residual symptoms other than insomnia present, and overall good tolerability, as assessed by the MGH-ATRQ, and this must include the participant's current antidepressant treatment
• Is receiving and tolerating well any one of the following SSRI or SNRI for depressive symptoms at screening, in any formulation and available in the participating country: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable dose (at therapeutic dose level) for at least 6 weeks
• Having a major depressive episode of at least moderate severity, as assessed with 17-item Hamilton Depression Rating Scale, implemented through the Structured Interview Guide (SIGH-D) in a blinded manner at screening and must not demonstrate a clinically 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 no additional 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 the investigator.
• 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, severe renal insufficiency clinically significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrine disorders 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 of significant medical disorders of the HPA axis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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752 participants in 5 patient groups, including a placebo group

Part 1: Seltorexant

Experimental group

Description:

Participants will receive seltorexant orally once daily for 6 weeks during the double-blind (DB) treatment phase in Part 1 of the study. Participants who do not proceed to Part 2 of the study will undergo a post-treatment follow-up phase, after the DB treatment phase in Part 1 and will continue to take their single baseline selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant throughout the study.

Treatment:

Drug: Seltorexant

Drug: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

Part 1: Placebo

Placebo Comparator group

Description:

Participants will receive matching placebo orally once daily for 6 weeks during the DB treatment phase in Part 1 of the study. Participants who do not proceed to Part 2 of the study will undergo a post-treatment follow-up phase, after the DB treatment phase in Part 1 and will continue to take their single baseline SSRI/SNRI antidepressant throughout the study.

Treatment:

Drug: Placebo

Drug: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

Part 2: Open Label (OL) Seltorexant

Experimental group

Description:

All participants who complete Part 1, and who meet eligibility criteria for Part 2, as well as direct entry participants, will enter Part 2 of the study. In Part 2 open-label phases (induction and stabilization) all participants (newly enrolled direct entry participants and Part 1 roll-over participants) will receive seltorexant orally in addition to their background SSRI/SNRI treatment.

Treatment:

Drug: Seltorexant

Drug: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

Part 2: DB Seltorexant

Experimental group

Description:

All participants who complete Part 1, and who meet eligibility criteria for Part 2, as well as direct entry participants, will enter Part 2 of the study. Participants who achieve a stable response during the open-label phase will receive treatment with seltorexant orally once daily during DB Maintenance Phase in Part 2 of the study. Participants will continue to take their single baseline SSRI/SNRI antidepressant throughout the study.

Treatment:

Drug: Seltorexant

Drug: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

Part 2: DB Placebo

Placebo Comparator group

Description:

All participants who complete Part 1, and who meet eligibility criteria for Part 2, as well as direct entry participants, will enter Part 2 of the study. Participants who achieve a stable response during the open-label phases will receive treatment with matching placebo orally once daily during DB Maintenance Phase in Part 2 of the study. Participants will continue to take their single baseline SSRI/SNRI antidepressant throughout the study.

Treatment:

Drug: Placebo

Drug: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)