A comparison of Esketamine Nasal Spray versus Quetiapine Extended-Release.
- Conditions
- Treatment-Resistant Major Depressive DisorderMedDRA version: 21.1Level: LLTClassification code 10081270Term: Major depressive disorderSystem Organ Class: 100000004873Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2019-002992-33-FI
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 622
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. male or female, 18 years (or older if the minimum legal age of consent in the country in which the study is taking place is >18 years) to 74 years of age, inclusive, at the time of signing the ICF.
2. at screening, each participant must meet DSM-5 diagnostic criteria for single-episode MDD or recurrent MDD, without psychotic features, based on clinical assessment and confirmed by the MINI.
3. at screening and baseline, each participant must have an IDS-C30 total score of =34.
4. must be on a current antidepressive treatment that includes an SSRI/SNRI at screening that resulted in nonresponse (less than 25% improvement of symptoms) after having been given at an adequate dosage (been uptitrated to maximum tolerated dose; based on antidepressive dosages from SmPC [or local equivalent, if applicable]) for an adequate duration of at least 6 weeks; however, at screening the participant must show signs of minimal clinical improvement to be eligible for the study.
Clinical improvement of a participant on their current AD treatment will be retrospectively evaluated in a qualified psychiatric interview performed by an experienced clinician.
At baseline (Day 1) prior to randomization, the investigator will evaluate any changes in the participant’s signs/symptoms of depression since the screening assessment and confirm that the inclusion criteria for the current AD treatment are still met (ie, nonresponse and minimal clinical improvement).
5. must be documented during screening that in addition to the current antidepressive treatment, the participant has had nonresponse within the current moderate to severe depressive episode to at least 1 but not more than 5 different, previous consecutive treatments with ADs taken at an adequate dosage for an adequate duration of at least 6 weeks and that each prior AD treatment did not produce any significant improvement (less than 25% improvement of symptoms).
6. must have been treated with at least 2 different antidepressive substance classes among the failed treatments in the current moderate to severe depressive episode (including the current treatment with an SSRI/SNRI).
7. must be on a single oral SSRI/SNRI on Day 1 prior to randomization.
Participants who are taking combination ADs and/or augmentation at screening are eligible for the study. All AD treatments, including any augmenting substances, must be stopped prior to randomization on Day 1 according to applicable SmPCs (or local equivalents, if applicable), except the SSRI/SNRI to be continued;
8. must be medically stable based on physical examination, medical history, vital signs (including blood pressure) at screening. If there are any abnormalities that are not specified in the inclusion and exclusion criteria, their clinical significance must be determined by the investigator and recorded in the participant’s source documents.
9. must be comfortable with self-administration of nasal medication and be able to follow the nasal administration instructions provided.
10. must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
11. must sign a separate ICF at baseline (Day 1) visit if he or she agrees to provide optional biomarker and/or genomic (DNA and RNA) samples for research (where local regulations permit). Refusal to give consent for the optional bi
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. received treatment with esketamine or ketamine in the current moderate to severe depressive episode.
2. received treatment with quetiapine extended- or immediate-release in the current moderate to severe depressive episode of a dose higher than 50 mg/day.
3. had depressive symptoms in the current moderate to severe depressive episode that previously did not respond to an adequate course of treatment with electroconvulsive therapy (ECT), defined as at least 7 treatments with unilateral/bilateral ECT.
4. has no signs of clinical improvement at all or with a significant improvement on their current AD treatment that includes an SSRI/SNRI as determined at screening by an experienced clinician during the qualified psychiatric interview.
5. received vagal nerve stimulation or has received deep brain stimulation in the current episode of depression.
6. has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the MINI), intellectual disability, autism spectrum disorder, borderline personality disorder, or antisocial personality disorder.
7. age at onset of first episode of MDD was =55 years.
8. has homicidal ideation or intent, per the investigator’s clinical judgment; or has suicidal ideation with some intent to act within 1 month prior to screening, per the investigator’s clinical judgment; or based on the C-SSRS, corresponding to a response of Yes” 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 suicidal ideation, or a history of suicidal behavior within the past year prior to screening. Participants reporting suicidal ideation with intent to act or suicidal behavior prior to the start of the acute phase should also be excluded.
9. history of moderate or severe substance use disorder or severe alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 6 months before the start of the screening or current clinical signs.
10. history (lifetime) of ketamine, PCP, lysergic acid diethylamide (LSD), or 3,4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related use disorder.
11. has a neurodegenerative disorder (eg, Alzheimer’s disease, vascular dementia, Parkinson’s disease with clinical evidence of cognitive impairment) or evidence of mild cognitive impairment.
12. is currently suffering from seizures, has a history of epilepsy, Neuroleptic Malignant Syndrome, or Tardive Dyskinesia.
13. has one of the following cardiovascular-related conditions:
(a). cerebrovascular disease with a history of stroke or transient ischemic attack.
(b). aneurysmal vascular disease (including intracranial, thoracic, or abdominal aorta, or peripheral arterial vessels).
(c). history of intracerebral hemorrhage.
(d). coronary artery disease with myocardial infarction, unstable angina, or revascularization procedure (eg, coronary angioplasty or bypass graft surgery) within 12 months before baseline (Day 1). Participants who have had a revascularization performed >12 months prior to screening and are clinically stable and symptom-free, per investigator’s clinical judgment, can be included.
(e). uncontrolled brady- or tachyarrhythmias that lead to hemodynamic instability.
(f). hemodynamically significant valvular heart disease such as mitra
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