A Study of the Efficacy and Safety of Intranasal Esketamine in the Rapid Reduction of Symptoms of Major Depressive Disorder, in Adults at Imminent Risk for Suicide
- Conditions
- Major Depressive Disorder with Imminent Risk of SuicideMedDRA version: 20.1Level: PTClassification code 10042458Term: Suicidal ideationSystem Organ Class: 10037175 - Psychiatric disordersMedDRA version: 20.0Level: PTClassification code 10057840Term: Major depressionSystem Organ Class: 10037175 - Psychiatric disordersMedDRA version: 20.0Level: PTClassification code 10012397Term: Depression suicidalSystem Organ Class: 10037175 - Psychiatric disordersMedDRA version: 20.0Level: PTClassification code 10065604Term: Suicidal behaviourSystem Organ Class: 10037175 - Psychiatric disordersTherapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2016-003992-23-PL
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 230
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. Criterion modified per Amendment RS-1 Group 1
6.1. As part of standard of care treatment, subject agrees to be hospitalized voluntarily for a recommended period of 14 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 after the last dose of study drug.
11. A woman of childbearing potential must have a negative urine pregnancy test at screening.
12. During the study (ie, from Day 1 of the double-bl
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. Criterion modified per Amendment RS-1 Group 1
5.1. Subject meets the DSM-5 severity criteria for moderate or severe substance or alcohol use disorder (except for nicotine or caffeine) within the 12 months before screening. A history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related use disorder is exclusionary.
6. Subject has a history or current signs and symptoms of liver or renal insufficiency or of clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic (including current or past history of seizures except uncomplicated childhood febrile seizures with no sequelae), hematologic, rheumatologic, or metabolic disease.
7. 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.
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 screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered to have minimal risk of recurrence).
10. Subject has any anatomical or medical condition that, per the investigator’s clinical judgment based on assessment, may impede delivery or absorption of intranasal study drug.
11. Subject has known allergies, hypersensitivity, intolerance or contraindications to esketamine or ketamine or its excipients (refer to Investigator's Brochure for esketamine, Summary of Product Characteristics, US prescribing information).
12. Subject has taken any disallowed therapy(ies) as noted in Section 8, Prestudy and Concomitant Therapy, and Attachment 1 of the protocol.
13. Subject has received an investigational drug (including esketamine, ketamine, or investigational vaccines) or used an invasive investigational medical device within 60 days before the
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method