Major Depressive Disorder (MDD) MedDRA version: 20.0 Level: LLT Classification code 10025453 Term: Major depressive disorder NOS System Organ Class: 100000004873
Conditions
Interventions
Product Name: JNJ-42847922 10 mg
Product Code: JNJ-42847922
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Seltorexant
CAS Num
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or WONCBP, aged 18 to 70 years (inclusive). Note: Subjects should be at least 18 years of age or older as per the legal age of consent in the jurisdiction in which the study is taking place. A WONCBP is defined as: o Postmenopausal A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level (>40 IU/L or mIU/mL) in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. o Permanently sterile Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy. If reproductive status is questionable, additional evaluation should be considered. 2. Meet DSM-5 diagnostic criteria for MDD, without psychotic features (DSM-5 296.22, 296.23, 296.32, or 296.33), based upon clinical assessment and confirmed by the SCID-CT. In addition, their major depressive episode must be deemed “valid” using the SSQ interview administered by remote, independent raters. The length of the current depressive episode must be =18 months. 3. Have had an inadequate response to at least 1 but no more than 3 antidepressants (see the inclusion criterion below), administered at an adequate dose and duration in the current episode of depression, as measured by the MGH-ATRQ. An inadequate response is defined as 20% on their MADRS total score) from the screening to baseline visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 280 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Has a history of, or current signs and symptoms of, severe renal insufficiency (creatinine clearance <30 mL/min); moderate to severe hepatic insufficiency (Child-Pugh Score 7-9), significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic (including narcolepsy), hematologic, rheumatologic, immunologic or endocrine disorders (including uncontrolled hypo- or hyperthyroidism or diabetes, or insulin-dependent diabetes mellitus). Subjects with non-insulin dependent diabetes mellitus who are well-controlled (hemoglobin A1C [HbA1C] =7.5% and fasting glucose <126 mg/dL at screening) may be eligible to participate if otherwise medically healthy, and if on a stable regimen of glucose-lowering medications for at least 2 months prior to screening. 2. Has current signs/symptoms of hypothyroidism or hyperthyroidism (Subjects with known hypothyroidism who have been on stable treatment for at least 3 months prior to screening are required to have thyroid-stimulating hormone [TSH] and free thyroxine [FT4] obtained. Any subject with an elevated TSH should also have FT4 measured. In any case where the TSH value is out of range, but FT4 is normal, the findings should be discussed directly with the medical monitor before the subject is enrolled. If the FT4 value is out of range, the subject is not eligible. Subjects taking thyroid supplementation for antidepressant purposes are not allowed in the study). 3. Has signs and symptoms of Cushing’s Disease, Addison’s Disease, primary amenorrhea, or other evidence of significant medical disorders of the HPA axis. 4. Has a current or recent history of serious suicidal ideation within the past 6 months, corresponding to a positive response on item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) for ideation on the C-SSRS, or a history of suicidal behavior within the past year, as validated by the C SSRS at screening or Day 1. Subjects with a prior suicide attempt of any sort, or prior serious suicidal ideation/plan within the past 6 months, should be carefully screened for current suicidal ideation and only subjects with non-serious items (1-3 of the suicidal ideation section of the C-SSRS) may be included at the discretion of the investigator. 5. Has a history of lack of response to 3 or more adequate antidepressant treatments, as indicated by no or minimal (=25% improvement in symptoms) when treated with an antidepressant of adequate dose (per MGH-ATRQ) and duration (at least 4 weeks).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the dose-response relationship of up to 3 doses of JNJ 42847922 (20 and 40 mg, with 10 mg potentially added at the interim analysis) compared to placebo as adjunctive therapy to an antidepressant drug in improving depressive symptoms in subjects with MDD who have had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). 2. To assess the safety and tolerability of JNJ 42847922 compared to placebo as adjunctive therapy to an antidepressant in subjects with MDD. ; Secondary Objective: To assess the efficacy of JNJ-42847922 compared to placebo as adjunctive therapy to an antidepressant in improving: 1. Depressive symptoms in subjects with MDD with significant insomnia symptoms (baseline Insomnia Severity Index [ISI] score =15) versus those without significant insomnia symptoms (baseline ISI score <15). 2. Response and remission of depressive symptoms, Anxiety symptoms, Response of anxiety symptoms, Clinical severity, Global functioning (work/school, social and family life). 3. Depressive symptoms in the subpopulation of subjects with MDD with anxious distress 4. To evaluate the effect of JNJ-42847922 exposure on the HPA axis in subjects with MDD 5. To assess the exposure of JNJ-42847922 and metabolites M12 and M16 in subjects with MDD 6 To capture patient-reported assessment of JNJ 42847922 compared to placebo as adjunctive therapy to an antidepressant ; Primary end point(s): 1. Change from baseline to the end of Week 6 in the MADRS total score. 2. Safety assessments, including adverse events, laboratory values, electrocardiogram (ECG), vital signs, physical exam, the Columbia Suicide Severity Rating Scale (C-SSRS), the Arizona Sexual Experiences Scal | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Correlation between baseline ISI score as a continuous variable and change from baseline to the end of Week 6 in the MADRS total score. 2. Change from baseline to the end of Week 6 in the MADRS total score in subjects with baseline ISI score =15 versus subjects with baseline ISI score <15. 3. Shift in ISI score category from baseline to the end of Week 6. 4. Proportion of responders on depressive symptoms scale, defined as a =50% improvement in MADRS total score from baseline to the end of Week 6. 5. Proportion of subjects with remission of depressive symptoms, defined as a MADRS total score =8, =10, or =12 at the end of Week 6. 6. Change from baseline to the end of Week 6 on the 14-item Hamilton Anxiety Rating scale (HAM-A) total score. 7. Proportion of responders on anxiety symptoms scale, defined as a =50% improvement in the HAM-A total score from baseline to the end of Week 6. 8. Change from baseline to the end of Week 6 in the Clinical Global Impression-Severity (CGI-S) score. 9. Change from baseline to the end of Week 6 in the Sheehan Disability Scale (SDS). 10. Change from baseline to the end of Week 6 in the MADRS total score in subjects with MDD with anxious distress versus subjects with MDD without anxious distress. 11. Change from baseline to Weeks 2, 4, and 6 in salivary cortisol levels, as measured upon awakening. 12. Observed plasma concentrations of JNJ 42847922 and metabolites and estimated exposure parameters for JNJ-42847922 from population based pharmacokinetic (PK) modeling. 13. Change from baseline to the end of Week 6 in: - Depressive symptoms using the Patient Health Questionnaire 9-item (PHQ-9) -Anhedonia using the Snaith-Hamilton Pleasure Scale (SHAPS) -Sleep dist | — |
Countries
Bulgaria, Finland, France, Germany, Japan, Russian Federation, Ukraine, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed