Clinical trial NCT04951609: A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adolescents With Major Depressive Disorder Who Have an Inadequate Response to Selective Serotonin Reuptake Inhibitor (SSRI) and Psychotherapy
Official title: A Short-term Exploratory Study to Evaluate Safety, Tolerability and Pharmacokinetics of Seltorexant as Adjunctive Therapy to Antidepressants in Adolescents With Major Depressive Disorder Who Have an Inadequate Response to SSRI Monotherapy and Psychotherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Depressive Disorder, Major
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-07-07
Enrollment: 31
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and tolerability of Seltorexant as adjunctive therapy to an antidepressant in adolescents with major depressive disorder (MDD) in the short-term compared with placebo.

Detailed description: The prevalence of major depression is approximately 4 percentage (%) to 8% in adolescents, with the highest incidence of MDD in child onset depression occurring during mid- to late adolescence (that is, 14 to 18 years of age). Seltorexant (JNJ-42847922) is a potent and selective antagonist of the human orexin-2 receptor (OX2R) that is being developed for the treatment of adjunctive treatment of MDD with insomnia symptoms (MDDIS).The study will be conducted in 3 phases: a screening phase (up to 30 days prior to first dose administration), a double-blind (DB) treatment phase (6 weeks), and a follow-up phase (up to 2 weeks including a telephone consult and on-site follow-up visit. The total study duration for each participant will be up to 12 weeks. Efficacy, safety, pharmacokinetics, and biomarkers will be assessed at specified time points during this study. The hypothesis for this study is that the safety, tolerability, and pharmacokinetics in the adolescent MDD population. There is no formal statistical hypothesis testing due to the exploratory and descriptive nature of this study.

Eligibility criteria: Inclusion Criteria:

* Has inadequate response to trial of at least 1, but no more than 2 antidepressant treatments during the current major depressive episode including their current antidepressant fluoxetine or escitalopram (SSRI). Inadequate response is determined as less than (\<) 50 percentage (%) symptom reduction after adequate antidepressant treatment for at least 6 weeks at or above the minimum therapeutic dose prior to screening
* Has had access to adequate psychotherapy in the current depressive episode (based on investigator judgement/local guidance) prior to randomization
* Must have Children's Depression Rating Scale-Revised (CDRS-R) total score greater than or equal to (\>=) 48 at screening and \>=40 at the baseline visit
* Participants weighing between fifth and ninety-fifth percentile for age and sex. Obese participants greater than ninety-fifth percentile and underweight participants below fifth percentile may participate following medical clearance, as long as their baseline weight is \>=30 kilograms (kg)
* A female participant of childbearing potential must have a negative urine pregnancy test at screening and baseline

Exclusion Criteria:

* Has a history of liver or renal insufficiency, significant cardiac (example, congenital heart disease, cardiomyopathy, or tachyarrhythmias), vascular, pulmonary, gastrointestinal, endocrine (including uncontrolled hyperthyroidism), neurologic (including seizure disorder), hematologic, rheumatologic, psychiatric, or metabolic disturbances. Stable medical conditions are allowed
* Has current the diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) diagnosis of conduct disorder, intellectual disability, autism spectrum disorder, borderline personality disorder, somatoform disorders, or fibromyalgia. A prior history of one or more of these disorders is allowed as long as the disorder(s) are currently stable and major depressive disorder (MDD) is not secondary to the original diagnosis. Has a current or prior DSM-5 diagnosis of a psychotic disorder, or bipolar disorder
* Has a significant primary sleep disorder (example, obstructive sleep apnea, parasomnias) at screening but participants with insomnia or hypersomnia disorders are allowed
* At significant risk of committing suicide based on history or according to the investigator's experience, or based on active suicidal ideation, intent or plan, item 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past 3 months or a history of suicidal behavior within the last 6 months
* Has known allergies, hypersensitivity, or intolerance to seltorexant or its excipients

Primary outcomes:
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 12 weeks
measure: Number of Participants with Adverse Event of Special Interest (AESIs)
timeFrame: Up to 12 weeks
measure: Pediatric Adverse Event Rating Scale (PAERS)
timeFrame: Up to 12 weeks
measure: Number of Participants with Abnormalities in Clinical Laboratory Values
timeFrame: Up to 6 weeks
measure: Number of Participants with Abnormalities in Electrocardiogram (ECG)
timeFrame: up to 6 weeks
measure: Number of Participants with Abnormalities in Vital Signs
timeFrame: Up to 12 weeks
measure: Number of Participants with Abnormalities in Physical Examination
timeFrame: Up to 6 weeks
measure: Suicidality Assessment Using the Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Up to 12 weeks
measure: Withdrawal Symptoms Assessment Using the Physician Withdrawal Checklist (PWC-20)
timeFrame: 2 weeks
measure: Number of Participants with Menstrual Cycle Tracking
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: Change from Baseline to Week 6/End of Treatment (EOT) in the Children's Depression Rating Scale (CDRS) Total Score
timeFrame: Baseline up to 6 weeks
measure: Change from Baseline to Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Score
timeFrame: Baseline up to 6 weeks
measure: Change from Baseline in Clinical Global Impression- severity (CGI-S) Score Over Time
timeFrame: Baseline up to 6 weeks
measure: Change from Baseline to Week 6/EOT on Subjective Sleep Assessment (Patient Reported Outcome Measurement Information System-Pediatric-Sleep Disturbance [PROMIS-Pediatric-SD] [Short Form 8a])
timeFrame: Baseline up to 6 weeks
measure: Change from Baseline to Week 6/EOT on Objective Sleep Assessment Actigraphy
timeFrame: Baseline up to 6 weeks
measure: Cognitive Performance on a Neurocognitive Battery at Baseline and Week 6/EOT
timeFrame: Baseline, Week 6
measure: Change in Subjective Sleep Related Impairment (PROMIS-Pediatric- Sleep-Related Impairment [SRI])
timeFrame: Up to 6 weeks
measure: Plasma Concentration of Seltorexant
timeFrame: Up to 6 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Autism Research and Resource Center
state: Arizona
city: Anaheim
country: United States
facility: Advanced Research Center Inc
state: California
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Orlando
country: United States
facility: APG Research LLC
state: Florida
city: Naperville
country: United States
facility: Baber Research Group
state: Illinois
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: West Chester
country: United States
facility: CincyScience
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of The Woodlands
state: Texas
city: Genova
country: Italy
facility: G.Gaslini Institute
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambin Gesù
city: Roma
country: Italy
facility: Universita Cattolica del Sacro Cuore - Fondazione Policlinico Universitario 'A. Gemelli'
city: Esplugues de Llobregat
country: Spain
facility: Hosp. Sant Joan de Deu
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Clinica Univ. de Navarra Madrid
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Majadahonda
country: Spain
facility: Hosp. Univ. Pta. de Hierro Majadahonda
city: Sabadell
country: Spain
facility: Corporacio Sanitari Parc Tauli
city: London
country: United Kingdom
facility: South London and Maudsley NHS Foundation Trust of The Maudsley Hospital
city: Oxford
country: United Kingdom
facility: Warneford Hospital, NIHR Clinical Research Facility
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: