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

NCT04451187 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: CR10876242847922MDD10052019-004913-15
• Study Type: interventional
• Target: 63
• Locations: 2 countries
• Sites: 2

Brief Summary

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).

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Driving Performance as Assessed by the Mean Difference of SDLP From an on-road Driving Test

  Day 2 and Day 9

• Participant Driving Performance as Assessed by Visual Analog Scale

  Day 2 and Day 9

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Up to 20 weeks

Study Arms (4)

Treatment Sequence CADB

EXPERIMENTAL

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; Drug: Seltorexant Dose 2; Drug: Placebo; Drug: Zopiclone

Treatment Sequence ABCD

EXPERIMENTAL

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; Drug: Seltorexant Dose 2; Drug: Placebo; Drug: Zopiclone

Treatment Sequence BDAC

EXPERIMENTAL

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; Drug: Seltorexant Dose 2; Drug: Placebo; Drug: Zopiclone

Treatment Sequence DCBA

EXPERIMENTAL

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; Drug: Seltorexant Dose 2; Drug: Placebo; Drug: Zopiclone

Interventions

Seltorexant Dose 1 DRUG

Participants will receive Dose 1 of seltorexant OD from Day 1 to Day 8 as part of Treatment A as per assigned treatment sequence.

Also known as: JNJ-42847922

Treatment Sequence ABCD; Treatment Sequence BDAC; Treatment Sequence CADB; Treatment Sequence DCBA

Seltorexant Dose 2 DRUG

Participants will receive Dose 2 of seltorexant OD from Day 1 to Day 8 as part of Treatment D as per assigned treatment sequence.

Also known as: JNJ-42847922

Treatment Sequence ABCD; Treatment Sequence BDAC; Treatment Sequence CADB; Treatment Sequence DCBA

Placebo DRUG

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.

Treatment Sequence ABCD; Treatment Sequence BDAC; Treatment Sequence CADB; Treatment Sequence DCBA

Zopiclone DRUG

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.

Treatment Sequence ABCD; Treatment Sequence BDAC; Treatment Sequence CADB; Treatment Sequence DCBA

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (2)

Anima

Alken, 3570, Belgium

Location

Universitaetsklinikum der RWTH Aachen

Aachen, 52074, Germany

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

seltorexant; zopiclone

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: June 30, 2020
• Study Start: July 16, 2020
• Primary Completion: March 16, 2023
• Study Completion: March 16, 2023
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

BE (1); DE (1)