A Double-blind, Randomized, Psychoactive Placebo-controlled, Study to Evaluate the Efficacy and Safety of 3 Fixed Doses (28 mg, 56 mg and 84 mg) of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Pediatric Subjects Assessed to be at Imminent Risk for Suicide
Study ID: STU 022017-069
This Phase 2 study is a randomized, double-blind, double-dummy, psychoactive placebocontrolled, multicenter trial with 45 anticipated global sites. a target of 145 male and female subjects, 12 to [Less Than]18 years of age, will be enrolled in this study and randomized in a 1:1:1:2 ratio to one of 3 doses of intranasal esketamine (28, 56 or 84 mg) or a psychoactive placebo (oral midazolam 0.125 mg/kg), with approximately 29 subjects assigned to each dose of intranasal esketamine and approximately 58 subjects assigned to psychoactive placebo. all eligible subjects will have a diagnosis of MDD, and will have presented to an emergency room (eR) or other permitted setting and been assessed to be at imminent risk for suicide. Given the vulnerability of the population, this study will be conducted in the context of standard of care treatment. This includes initial hospitalization in an inpatient psychiatric unit or other permitted setting for a recommended duration of 5 days, with shorter or longer hospitalizations permitted if clinically warranted per local standard of care; initiation or optimization of antidepressant treatment; participation in a specific psychological intervention (individual cognitive behavioral therapy [CBT]), interpersonal therapy, family therapy or psychodynamic psychotherapy) close outpatient follow-up.
1. Male and female adolescents (12 to 17 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 International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) 3. Subject must have current suicidal ideation with intent, confirmed by a * Yes * response to MINI-KID: Question B3 [Think about hurting yourself, with the possibility that you might die? Or did you think about killing yourself?] AND Question B10 [Expect to go through with a plan to kill yourself?] Note: the response to B3 must refer to the present, whereas the response to B10 mayreflect the past 24 hours. If screening is longer than 24 hours, the assessment ofquestions B3 and B10 for the MINI-KID must be repeated and to confirm eligibility. 4. In the physician[Single Quote]s opinion, acute psychiatric hospitalization is clinically warranted due to subject[Single Quote]s imminent risk for suicide 5. Subject must have a Children[Single Quote]s Depression Rating Scale-Revised (CDRS-R) total score >=58 at baseline 6. As part of standard of care treatment, subject must agree to -be hospitalized voluntarily for a recommended period of 5 days after randomization (may be shorter or longer if clinically warranted in the investigator[Single Quote]s opinion), -take prescribed non-investigational antidepressant therapy (fluoxetine, escitalopram or sertraline) for at least the duration of the double-blind treatment phase (Day 25), -participate in a specific psychosocial intervention (individual cognitive behavioral therapy [CBT], interpersonal therapy, family therapy or psychodynamic psychotherapy) at least through the initial 8-week follow-up period (Day 81). 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. Note: Subjects recovering from a recent suicide attempt may be eligible provided they are medically stable. 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. -Incidental exclusionary laboratory values (""incidental"" refers to duplicate results from a separate blood sample analyzed at the central laboratory that become available after the subject has satisfied the inclusion and exclusion criteria based on the local laboratory values) will be handled on a case-by-case basis to determine if the subject should be withdrawn from the study. 10. During the double-blind phase, a heterosexually active female must: -practice a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) and - agree to continue to use a highly effective method throughout the study and for at least 6 weeks after the last dose of study drug. Examples of highly effective contraceptives include: implantable progestogen-only hormone contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); vasectomized partner; combined (estrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, and transdermal; progestogen-only hormone contraception associated with inhibition of ovulation: oral and injectable. Contraceptive use by males or females should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies. 12. Females must have a negative urine pregnancy test at Screening 13.During the double-blind phase (from Day 1 through day of last dose of study drug)) and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study drug, a male subject who is heterosexually active -must be practicing a highly effective method of contraception with his female partner from those listed above (see examples of highly effective methods of contraception provided for female subjects). -must use a condom if his partner is pregnant - must agree not to donate sperm. 14. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol. 15. Subject[Single Quote]s parent(s) or legally acceptable representative(s) [(LAR(s)] must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to allow the subject to participate in the study. Assent is also required of subjects 16. Subject[Single Quote]s parent(s) or legally acceptable representative(s) [(LAR(s)] must sign a separate informed consent form if he or she agrees to have the subject provide an optional DNA/RNA sample for research (where local regulations permit). Assent is also required from the subject as described in Section 16.2.3 Informed Consent/Pediatric Assent. Refusal to give consent/assent for the optional DNA/RNA research sample does not exclude a subject from participation in the study.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- GRAHAM JOHN EMSLIE
JANSSEN RESEARCH AND DEVELOPMENT LLC
Primary objective: The primary objective is to assess the efficacy of a single (first) dose of 3 fixed doses of intranasal esketamine (28 mg, 56 mg, and 84 mg) compared with psychoactive placebo (oral midazolam) in rapidly reducing the symptoms of MDD, including suicidal ideation, in subjects 12 to [Less Than]18 years of age who are assessed to be at imminent risk for suicide. efficacy will be assessed by the change from baseline in Children's Depression Rating Scale, Revised (CDRS-R) total score at 24 hours post first dose (Day 2).