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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 31
- 试验地点
- 23
- 主要终点
- Pediatric Adverse Event Rating Scale (PAERS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Seltorexant
Participants will receive weight based dose of Seltorexant orally once daily from Day 1 to Day 42 (until the end of Week 6). Participants will continue baseline selective serotonin reuptake inhibitor (SSRI) antidepressant (Fluoxetine or escitalopram) orally once daily.
干预措施: Seltorexant (Drug)
Placebo
Participants will receive matching placebo tablets to seltorexant orally once daily from Day 1 to Day 42 (until the end of Week 6).
干预措施: Placebo (Drug)
结局指标
主要结局
Pediatric Adverse Event Rating Scale (PAERS)
时间窗: Up to 12 weeks
The PAERS is a patient-rated scale designed to assess adverse events occurring in pediatric participants treated with psychotropic medication in clinical studies. Individual PAERS (patient-reported version) will rate symptoms and severity of symptoms. This scale has a total of 48 items. There is no overall score and individual item will be rated on a scale of 0 to 4 in which 0 indicates 'not present' and 4 indicates 'very bothersome/an extreme problem'.
Number of Participants with Abnormalities in Electrocardiogram (ECG)
时间窗: up to 6 weeks
Number of participants with abnormalities in ECG will be reported.
Number of Participants with Abnormalities in Physical Examination
时间窗: Up to 6 weeks
Number of participants with abnormalities in physical examination including weight will be reported.
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to 12 weeks
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are adverse events with onset during the double-blind treatment phase or that are a consequence of a preexisting condition that has worsened since baseline.
Number of Participants with Abnormalities in Vital Signs
时间窗: Up to 12 weeks
Number of participants with abnormalities in vital sign(blood pressure and pulse/heart rate) will be reported.
Suicidality Assessment Using the Columbia Suicide Severity Rating Scale (C-SSRS) Score
时间窗: Up to 12 weeks
Suicidality assessment using the C-SSRS will be reported. C-SSRS is a clinician rated assessment of suicidal behavior and/ or intent. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 yes/no items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Worsening of suicidal ideation will be an increase in severity of suicidal ideation from baseline.
Withdrawal Symptoms Assessment Using the Physician Withdrawal Checklist (PWC-20)
时间窗: 2 weeks
Withdrawal symptoms assessment using the PWC-20 will be reported. The PWC-20 is a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 is a reliable and sensitive instrument for the assessment of discontinuation symptoms. Each individual item score ranges from 0 (not present) to 3 (severe), where higher scores = more affected condition.
Number of Participants with Menstrual Cycle Tracking
时间窗: Up to 6 weeks
Number of participants with menstrual cycle tracking will be reported. Menstrual cycles will be tracked during the study in female adolescents or participants who have at least one menses using a participant diary and participant's verbal report.
Number of Participants with Adverse Event of Special Interest (AESIs)
时间窗: Up to 12 weeks
Number of participants with AESIs will be reported. AEs are considered to be of special interest in this study: a) Cataplexy (sudden, transient episode of muscle weakness accompanied by conscious awareness); b) Sleep paralysis (the experience of not being able to move, react, or speak when falling asleep/awakening); c) Complex, sleep-related behaviors/parasomnias such as confusional arousals, somnambulism (sleep walking), sleep terrors, bruxism (teeth grinding), sleep sex, sleep-related eating disorder, and catathrenia (REM-associated end-inspiratory apnea/breath holding); d) Any new suicidal behavior or suicidal ideation.
Number of Participants with Abnormalities in Clinical Laboratory Values
时间窗: Up to 6 weeks
Number of participants with abnormalities in clinical laboratory values (hematology, serum chemistry and urinalysis) will be reported.
次要结局
- Change from Baseline to Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Score(Baseline up to 6 weeks)
- Plasma Concentration of Seltorexant(Up to 6 weeks)
- Change from Baseline in Clinical Global Impression- severity (CGI-S) Score Over Time(Baseline up to 6 weeks)
- Change from Baseline to Week 6/End of Treatment (EOT) in the Children's Depression Rating Scale (CDRS) Total Score(Baseline up to 6 weeks)
- Change from Baseline to Week 6/EOT on Objective Sleep Assessment Actigraphy(Baseline up to 6 weeks)
- Change in Subjective Sleep Related Impairment (PROMIS-Pediatric- Sleep-Related Impairment [SRI])(Up to 6 weeks)
- 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])(Baseline up to 6 weeks)
- Cognitive Performance on a Neurocognitive Battery at Baseline and Week 6/EOT(Baseline, Week 6)