A Study of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants With Treatment-resistant Depression
Depressive Disorder, Treatment-Resistant
About this trial
This is an interventional treatment trial for Depressive Disorder, Treatment-Resistant
Eligibility Criteria
Inclusion Criteria:
- Participant must meet the Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for single-episode MDD or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the MINI. Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age
- Participant must have had nonresponse (<=25% improvement) to >=2 oral antidepressant treatments in the current episode of depression, assessed using the MGH-ATRQ, and confirmed by documented records (example, medical/pharmacy/prescription records or a letter from a treating physician)
- Participant must have an Inventory of Depressive Symptomatology-Clinician rated, 30-item (IDS-C30) total score of >=34
- The participant's current major depressive episode, depression symptom severity, and antidepressant treatment response in the current depressive episode, must be confirmed by the State vs. Trait, Assessibility, Face Validity, Ecological Validity, Rule of Three P's (SAFER) Interview
- Participant must be medically stable on the basis of physical examination, medical history, vital signs (including blood pressure), and 12-lead electrocardiogram (ECG) performed in the screening phase. If there are any abnormalities that are not specified in the inclusion and exclusion criteria, the determination of their clinical significance must be determined by the investigator and recorded in the participant's source documents and initiated by the investigator
- Participant must be medically stable on the basis of clinical laboratory tests performed in the screening phase. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator: (a) Participants with a pre-existing history of thyroid disease/disorder who are treated with thyroid hormones must be on a stable dosage for 3 months prior to the start of the screening phase; (b) For any participant (regardless of thyroid history), if the thyroid-stimulating hormone (TSH) value is out of range, a free thyroxine (FT4) will be conducted. If the FT4 value is abnormal and considered to be clinically significant (after discussion with the medical monitor), the participant is not eligible
- Participant must be comfortable with self-administration of nasal spray medication and be able to follow the nasal spray administration instructions provided
Exclusion Criteria:
- The participant has used ketamine/esketamine (lifetime)
- The participant's depressive symptoms have previously demonstrated nonresponse to an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT
- Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression
- Participant has a current or history of seizures (uncomplicated childhood febrile seizures with no sequelae are not exclusionary)
- Participant has any anatomical or medical condition that, per the investigator's clinical judgment based on assessment, may impede delivery or absorption of nasal spray study drug
Sites / Locations
- UAB Department of Psychiatry and Behavioral NeurobiologyRecruiting
- UAB Huntsville Regional Medical CampusRecruiting
- Preferred Research PartnersRecruiting
- Behavioral Research Specialists, LLCRecruiting
- CalNeuro ResearchRecruiting
- Pacific Research Partners
- Anderson Clinical ResearchRecruiting
- University of California at San DiegoRecruiting
- Artemis Institute for Clinical ResearchRecruiting
- UCSF Nancy Friend Pritzker Psychiatry BuildingRecruiting
- Velocity Clinical ResearchRecruiting
- CMB Clinical TrialsRecruiting
- University of Connecticut Health CenterRecruiting
- Velocity Clinical Research, Hallandale Beach
- Accel Research SitesRecruiting
- APG Research, LLCRecruiting
- USF, Department of Psychiatry and Behavioral NeurosciencesRecruiting
- Neuroscience Research InstituteRecruiting
- Atlanta Behavioral Research, LLCRecruiting
- Psych Atlanta, P.C.Recruiting
- Rush University Medical CenterRecruiting
- Chicago Research CenterRecruiting
- University of ChicagoRecruiting
- Joliet Center for Clinical Research
- Pillar Clinical Research, LLC
- Psychiatric Medicine Associates LLCRecruiting
- Ascension via Christi ResearchRecruiting
- University of Kansas School of MedicineRecruiting
- Sheppard Pratt Health SystemRecruiting
- CBH HealthRecruiting
- Copley ClinicalRecruiting
- Adams ClinicalRecruiting
- University of Massachusetts Medical SchoolRecruiting
- University of Michigan
- Rochester Center for Behavioral Medicine (RCBM)Recruiting
- Midwest Research Group - St. Charles Psychiatric AssociatesRecruiting
- Clinilabs
- The Medical Research Network, LLCRecruiting
- Stony Brook University Medical CenterRecruiting
- Ohio State UniversityRecruiting
- Midwest Clinical Research CenterRecruiting
- Paradigm Research Professionals, LLCRecruiting
- Lehigh Center for Clinical ResearchRecruiting
- University of Pennsylvania Medical CenterRecruiting
- The Warren Alpert Medical School of Brown University - Butler HospitalRecruiting
- BioBehavioral Research of Austin, PCRecruiting
- Relaro Medical TrialsRecruiting
- University of Texas Southwestern Medical CenterRecruiting
- Brain Health Consultants and TMS CenterRecruiting
- The University of Texas Health Science Center at HoustonRecruiting
- Pillar Clinical Research, LLC
- Family Psychiatry of The WoodlandsRecruiting
- Grayline Research CenterRecruiting
- University of Virginia Center for Psychiatric Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Esketamine 56 Milligram (mg)
Esketamine 84 mg
Placebo
Participants will receive nasal spray treatment with esketamine 56 mg twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 Montgomery-Asberg Depression Rating Scale [MADRS] assessment).
Participants will receive nasal spray treatment with esketamine 84 mg twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 MADRS assessment).
Participants will receive nasal spray treatment with placebo twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 MADRS assessment).