A Study of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants With Treatment-resistant Depression
- Conditions
- Depressive Disorder, Treatment-Resistant
- Interventions
- Registration Number
- NCT04599855
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy of each individual dose of esketamine nasal spray, 56 milligram (mg) and 84 mg, compared with placebo nasal spray in improving depressive symptoms in participants with treatment resistant depression (TRD), as assessed by the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from Day 1 (prerandomization) to the end of the 4 week double-blind treatment phase (Day 28).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 477
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Esketamine 84 mg Esketamine 84 mg 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). Placebo Placebo 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). Esketamine 56 Milligram (mg) Esketamine 56 mg 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).
- Primary Outcome Measures
Name Time Method Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score from Day 1 (Pre-randomization) to the End of the 4-week Double-Blind Treatment Phase (Day 28) Baseline to Day 28 MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
- Secondary Outcome Measures
Name Time Method Change from Baseline in MADRS Total Score from Day 1 (Pre-randomization) to Day 2 Baseline to Day 2 MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Trial Locations
- Locations (53)
University of Chicago
🇺🇸Chicago, Illinois, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Lehigh Center for Clinical Research
🇺🇸Allentown, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Family Psychiatry of The Woodlands
🇺🇸The Woodlands, Texas, United States
Neuroscience Research Institute
🇺🇸West Palm Beach, Florida, United States
Accel Research Sites
🇺🇸Lakeland, Florida, United States
CBH Health
🇺🇸Gaithersburg, Maryland, United States
Midwest Research Group - St. Charles Psychiatric Associates
🇺🇸Saint Charles, Missouri, United States
Clinilabs
🇺🇸New York, New York, United States
Copley Clinical
🇺🇸Boston, Massachusetts, United States
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Preferred Research Partners
🇺🇸Little Rock, Arkansas, United States
Pacific Research Partners
🇺🇸Oakland, California, United States
APG Research LLC
🇺🇸Orlando, Florida, United States
University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Joliet Center for Clinical Research
🇺🇸Joliet, Illinois, United States
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
University of Kansas School of Medicine
🇺🇸Wichita, Kansas, United States
Ascension via Christi Research
🇺🇸Wichita, Kansas, United States
UAB Huntsville Regional Medical Campus
🇺🇸Huntsville, Alabama, United States
CalNeuro Research
🇺🇸Los Angeles, California, United States
Behavioral Research Specialists LLC
🇺🇸Glendale, California, United States
Anderson Clinical Research
🇺🇸Redlands, California, United States
University of California at San Diego
🇺🇸San Diego, California, United States
Artemis Institute for Clinical Research
🇺🇸San Diego, California, United States
Velocity Clinical Research
🇺🇸Santa Ana, California, United States
CMB Clinical Trials
🇺🇸Santee, California, United States
Atlanta Behavioral Research, LLC
🇺🇸Atlanta, Georgia, United States
Psych Atlanta, P.C.
🇺🇸Marietta, Georgia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Chicago Research Center
🇺🇸Chicago, Illinois, United States
Pillar Clinical Research, LLC
🇺🇸Richardson, Texas, United States
Psychiatric Medicine Associates LLC
🇺🇸Skokie, Illinois, United States
The Medical Research Network, LLC
🇺🇸New York, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Midwest Clinical Research Center
🇺🇸Dayton, Ohio, United States
University of Pennsylvania Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
The Warren Alpert Medical School of Brown University - Butler Hospital
🇺🇸Providence, Rhode Island, United States
Relaro Medical Trials
🇺🇸Dallas, Texas, United States
Brain Health Consultants and TMS Center
🇺🇸Houston, Texas, United States
Grayline Research Center
🇺🇸Wichita Falls, Texas, United States
University of Virginia Center for Psychiatric Clinical Research
🇺🇸Charlottesville, Virginia, United States
UAB Department of Psychiatry and Behavioral Neurobiology
🇺🇸Birmingham, Alabama, United States
UCSF Nancy Friend Pritzker Psychiatry Building
🇺🇸San Francisco, California, United States
Paradigm Research Professionals, LLC
🇺🇸Oklahoma City, Oklahoma, United States
USF, Department of Psychiatry and Behavioral Neurosciences
🇺🇸Tampa, Florida, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Rochester Center for Behavioral Medicine (RCBM)
🇺🇸Rochester Hills, Michigan, United States
Sheppard Pratt Health System
🇺🇸Baltimore, Maryland, United States
Velocity Clinical Research, Hallandale Beach
🇺🇸Hallandale Beach, Florida, United States
Adams Clinical
🇺🇸Watertown, Massachusetts, United States
BioBehavioral Research of Austin PC
🇺🇸Austin, Texas, United States