Major Depressive Disorder with Imminent Risk of Suicide MedDRA version: 20.0 Level: PT Classification code 10042458 Term: Suicidal ideation System Organ Class: 10037175 - Psychiatric disorders MedDRA version: 20.0 Level: PT Classification code 10057840 Term: Major depression System Organ Class: 10037175 - Psychiatric disorders
Conditions
Sponsors
Janssen-Cilag Internacional NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject must be a man or woman, 18 to 64 years of age, inclusive. 2. Subject must meet Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for MDD, without psychotic features, based upon clinical assessment and confirmed by the MINI. 3. Subjects must have current suicidal ideation with intent, confirmed by a “Yes” response to Question B3 [Think (even momentarily) about harming or of hurting or of injuring yourself: with at least some intent or awareness that you might die as a result; or think about suicide (ie, about killing yourself)?] AND Question B10 [Intend to act on thoughts of killing yourself?] obtained from the MINI. Note: the response to B3 must refer to the present, whereas the response to B10 may reflect the past 24 hours. If the screening period is longer than 24 hours, assessment of B3 and B10 of MINI must be repeated prior to randomization to confirm eligibility. 4. In the physician’s opinion, acute psychiatric hospitalization is clinically warranted due to subject’s imminent risk of suicide. 5. Subject has a MADRS total score of >28 predose on Day 1. 6. As part of standard of care treatment, subject agrees to be hospitalized voluntarily for a recommended period of 5 days after randomization (may be shorter or longer if clinically warranted in the investigator’s opinion) and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25). 7. Subject is comfortable with self-administration of intranasal medication and able to follow instructions provided. 8. Subject must be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening. If there are abnormalities, the subject may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator. 9. Subject must be medically stable on the basis of clinical laboratory tests performed by the local laboratory at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator. 10. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies. Before randomization, a woman must be either: a. Not of childbearing potential defined as: -postmenopausal (>45 years of age with amenorrhea for at least 12 months), permanently sterilized (eg, bilateral tubal occlusion/ligation procedures, hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy b. Of childbearing potential and -practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) -agrees to use a highly effective method throughout the study and for at least 6 weeks af
Exclusion criteria
Exclusion criteria: 1. Subject has a current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, or obsessive compulsive disorder. 2. Subject currently meets DSM-5 criteria for borderline personality disorder. -Subjects not meeting full DSM-5 criteria for borderline personality disorder but exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should also be excluded. 3. Subject has a current clinical diagnosis of autism, dementia, or intellectual disability. 4. Subject has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features. 5. Subject has a history of moderate or severe substance or alcohol use disorder, according to DSM-5 criteria, except nicotine or caffeine, within 6 months before screening. 6. Criterion modified per Amendment 1 6.1. Subject has any of the following conditions: -a history or current signs and symptoms of liver or renal insufficiency -clinically significant cardiac (including unstable coronary artery disease and congestive heart failure, tachyarrhythmias and recent myocardial infarction) or vascular, pulmonary, gastrointestinal, endocrine (including uncontrolled hyperthyroidism), neurologic (including current or past history of seizures except uncomplicated childhood febrile seizures with no sequelae), hematologic, rheumatologic, or metabolic (including severe dehydration/hypovolemia) disease. 7. Criterion modified per Amendment 1 7.1. Subject has uncontrolled hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) despite diet, exercise or a stable dose of anti-hypertensive treatment for at least 2 weeks at screening; or any past history of hypertensive crisis. -Subjects with conditions in which the elevation of blood pressure could be a serious risk (including unstable heart failure, severe cardiovascular disease, recent cerebral injury, increased intracranial pressure / intracranial mass lesion, intracranial bleeding or acute stroke, untreated glaucoma or perforating eye injury) are excluded. -An abnormal blood pressure value at screening can be repeated once after 5 minutes of relaxation for subject eligibility. On Day 1 of the double-blind phase prior to randomization, a supine or semi-supine systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg is exclusionary. 8. Subject has a positive urine test result(s) for phencyclidine (PCP), cocaine, or amphetamines at screening. -Subjects who have a positive test due to the appropriate use of prescribed opiates, benzodiazepines, or barbiturates may be eligible for study participation per clinician judgment. In addition, subjects who have a positive test for opiates, benzodiazepines, or barbiturates used without a prescription, may be considered eligible per clinician judgment and in consultation with the sponsor’s medical monitor. -Subjects who have a positive test due to opiates, benzodiazepines, or barbiturates taken in a suicide attempt (eg, overdose) may be eligible for study participation per clinician judgment and in consultation with the sponsor’s medical monitor. 9. Subject has a history of malignancy within 5 years before scr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy of intranasal esketamine 84 mg compared with intranasal placebo in addition to comprehensive standard of care in reducing the symptoms of MDD, including suicidal ideation, in subjects who are assessed to be at imminent risk for suicide, as measured by the change from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 24 hours post first dose.;Secondary Objective: The key secondary objective is to assess the efficacy of intranasal esketamine compared with intranasal placebo in reducing severity of suicidality as measured by the clinical global impression of severity of suicidality revised version (CGI-SS-R) at 24 hours post first dose. Other secondary objectives are listed in Protocol Section 2.1.1.;Primary end point(s): Change from baseline in depressive symptoms, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) total score;Timepoint(s) of evaluation of this end point: Day 1, predose to 24 hours post first dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Change from baseline in severity of suicidality, as measured by the clinical global impression of severity of suicidality revised version (CGI-SS-R) 2) Remission rate (MADRS =12) 3) Change from baseline of MADRS total score 4) Change from baseline of CGI-SS-R 5) Proportion of subjects achieving resolution of suicidality (CGI-SS-R score of 0 or 1) 6) Change from baseline of clinical global impression of imminent suicide risk (CGI SR-I) 7) Change from baseline of Beck Hopelessness Scale (BHS) 8) Change from baseline of European Quality of Life (EuroQol) Group, 5-Dimension, 5-Level (EQ-5D-5L) 9) Change from baseline of Quality of Life in Depression Scale (QLDS) 10) Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores 11) Suicidal Ideation and Behaviors Assessment Tool (SIBAT): Change from baseline in Module 3 My Current Thinking and Module 5 My Risk, Question 3 (patient-reported frequency of suicidal thinking) 12) Pharmacokinetics: Plasma esketamine and noresketamine concentrations will be summarized; plasma concentrations of esketamine (and noresketamine concentrations, if warranted) will be included in a population analysis 13) Safety endpoints will be evaluated throughout the study - Monitoring of treatment emergent adverse events (TEAEs), Clinical laboratory tests, physical examination, nasal examination, 12-lead electrocardiogram (ECG), and vital signs, SIBAT, On dosing days only: MOAA/S, CADSS, and pulse oximetry ; Timepoint(s) of evaluation of this end point: 1) From day 1, predose to 24 hours post first dose 2, 5, 6) 4 hours and 24 hours post first dose, and through the end of the double-blind treatment phase (Day 25) 3,4) 4 hours post first dose and through the end of | — |
Countries
Bulgaria, Estonia, Germany, Hungary, Korea, Republic of, Malaysia, Slovakia, South Africa, Spain, Taiwan, United States
Contacts
Public ContactGlobal Clinical Operations Spain
Janssen-Cilag, S.A
Outcome results
None listed