Clinical trial NCT01998958: A Study to Evaluate the Safety and Efficacy of Intranasal Esketamine in Treatment-resistant Depression
Official title: A Double-Blind, Doubly-Randomized, Placebo-Controlled Study of Intranasal Esketamine in an Adaptive Treatment Protocol to Assess Safety and Efficacy in Treatment-Resistant Depression (SYNAPSE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Treatment Resistant Depressive Disorder
Keywords: Treatment resistant depressive disorder
Intranasal esketamine
Efficacy
SYNAPSE
JNJ-54135419
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2013-12-03
Enrollment: 108
Sex: ALL
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and dose response of intranasal esketamine (Panel A: 28 mg, 56 mg, and 84 mg and Panel B: 14 mg and 56 mg) compared with placebo in improving depressive symptoms in participants with treatment-resistant depression (TRD).

Detailed description: This will be a 2-panel, randomized ( participants are assigned different treatments based on chance), double-blind (neither investigator nor participant knows which treatment the participant receives), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), multicenter study. Approximately 100 male and female adult participants diagnosed with TRD will participate in this study. For participants in both panels (Panel A and Panel B), there will be 4 study phases: a 4-week screening phase, a double-blind treatment phase (Day 1 to Day 15), an optional open-label treatment phase (Panel A: Day 15 to 74; Panel B: Day 15 to 25), and an 8-week post-treatment (follow-up) phase. Depending on the treatment Panel, patients will be assigned to intranasal placebo or intranasal esketamine 14 mg, 28 mg, 56 mg, or 84 mg. Safety assessments will be performed throughout the study. The maximum study duration for a participant will be 23 weeks for Panel A and 16 weeks for Panel B.

Eligibility criteria: Inclusion Criteria:

--Participant must meet Diagnostic and Statistical Manual of Mental Disorders -Fourth Edition -Text Revised (DSM-IV-TR) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment, and confirmed by the Mini International Neuropsychiatric Interview (MINI)-Participant's major depressive episode and treatment response must be deemed "valid" by remote independent raters-Participant must have had an inadequate response to at least 2 antidepressants, at least one of which is in the current episode of depression; the antidepressant treatment response questionnaire (ATRQ) will be used to assess antidepressant treatment response during the current episode; prior medication history will be used to determine antidepressant treatment response in prior episode(s) -Have an Inventory of Depressive Symptoms-Clinician rated, 30-item (IDS-C30) total score \>=34 at Screening and predose at Day 1

Exclusion Criteria:

-Participant has a current DSM-IV-TR diagnosis of bipolar and related disorders, intellectual disability, or cluster b personality disorder (e.g., borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder) -Participant has a current or prior DSM-IV-TR diagnosis of a psychotic disorder, MDD with psychosis, post-traumatic stress disorder (PTSD), or obsessive compulsive disorder (OCD) -Anatomical or medical conditions that may impede delivery or absorption of study medication (e.g., undergone facial reconstruction, rhinoplasty, significant structural or functional abnormalities of the nose or upper airway; obstructions or mucosal lesions of the nostrils or nasal passages; undergone sinus surgery in the previous 2 years; signs and symptoms of rhinitis) -Has an abnormal or deviated nasal septum with any 1 or more of the following symptoms: blockage of 1 or both nostrils, nasal congestion (especially 1-sided), frequent nosebleeds, frequent sinus infections, and at times has facial pain, headaches, and postnasal drip -Has a history of substance abuse (drug or alcohol) or dependence (except nicotine or caffeine) within the previous 1 year of the screening visit -Participant has known allergies, hypersensitivity, intolerance, or contraindication to esketamine/ketamine or its excipients

Primary outcomes:
measure: Panel A and B: Change From Baseline (Day 1) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Day 8- Analysis of Covariance (ANCOVA) Analysis
timeFrame: Baseline (Day 1) and Endpoint (Day 8) of Period 1
measure: Panel A and B: Change From Baseline (Day 8) in Montgomery Asberg Depression Rating Scale Total Score at Day 15- ANCOVA Analysis
timeFrame: Baseline (Day 8) and Endpoint (Day 15) of Period 2
Secondary outcomes:
measure: Panel A and B: Percentage of Participants With Sustained Response Based on MADRS Total Score in Participants Who Have Completed the Double-Blind Phase and Received the Same Treatment for Both Periods
timeFrame: Day 2 Up to Day 15
measure: Panel A and B: Percentage of Participants With Sustained Response Based on MADRS Total Score in Participants Who Received the Same Treatment for Both Periods, Including Participants Who Did Not Complete the Double-blind Phase
timeFrame: Day 2 Up to Day 15
measure: Panel A and B: Percentage of Participants With Response Based on MADRS Total Score
timeFrame: Period 1: Days 1 (2 hour), 2 and 8 of Double-blind Phase
measure: Panel A and B: Percentage of Participants With Response Based on MADRS Total Score
timeFrame: Period 2: Days 1 (2 hour), 2 and 8 of Double-blind Phase
measure: Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase
timeFrame: Days 1, 2 and 8 of Double-blind Phase of Period 1
measure: Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase
timeFrame: Days 1, 2 and 8 of Double-blind Phase of Period 2
measure: Panel A and B: Change From Baseline (Day 1) in Quick Inventory of Depressive Symptomatology-16-item Self Report (QIDS-SR16) Total Score at Day 8 in the Double-Blind Treatment Phase- ANCOVA Analysis
timeFrame: Baseline (Day 1) and Endpoint (Day 8) of Period 1
measure: Panel A and B: Change From Baseline (Day 8) in Quick Inventory of Depressive Symptomatology-16-item Self Report Total Score at Day 15 in the Double-Blind Treatment Phase- ANCOVA Analysis
timeFrame: Baseline (Day 8) and Endpoint (Day 15) of Period 2
measure: Panel A and B: Change From Baseline (Day 1) in Clinical Global Impression - Severity (CGI-S) Total Score at Day 8 in the Double-Blind Treatment Phase- ANCOVA Analysis on Ranks
timeFrame: Baseline (Day 1) and Endpoint (Day 8) of Period 1
measure: Panel A and B: Change From Baseline (Day 8) in Clinical Global Impression - Severity Total Score at Day 15 in the Double-Blind Treatment Phase- ANCOVA Analysis on Ranks
timeFrame: Baseline (Day 8) and Endpoint (Day 15) of Period 2
measure: Panel A and B: Change From Baseline (Day 1) in Generalized Anxiety Disorder (GAD-7) Total Score at Day 8 (Double-Blind Treatment Phase) ANCOVA Analysis
timeFrame: Baseline (Day 1) and Endpoint (Day 8) of Period 1
measure: Panel A and B: Change From Baseline (Day 8) in Generalized Anxiety Disorder-7 Total Score at Day 15 (Double-Blind Treatment Phase)- ANCOVA Analysis
timeFrame: Baseline (Day 8) and Endpoint (Day 15) of Period 2
measure: Panel A and B: Change From Baseline (Day 1) in Patient Global Impression of Severity (PGI-S) Score Total Score at Day 8 in the Double-Blind Treatment Phase- ANCOVA Analysis on Ranks
timeFrame: Baseline (Day 1) and Endpoint (Day 8) of Period 1
measure: Panel A and B: Change From Baseline (Day 8) in Patient Global Impression of Severity Score Total Score at Day 15 in the Double-Blind Treatment Phase- ANCOVA Analysis on Ranks
timeFrame: Baseline (Day 8) and Endpoint (Day 15) of Period 2
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Garden Grove
country: United States
state: California
city: Hartford
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Hoffman Estates
country: United States
state: Illinois
city: Rockville
country: United States
state: Maryland
city: Cedarhurst
country: United States
state: New York
city: New York
country: United States
state: New York
city: Allentown
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Memphis
country: United States
state: Tennessee
city: Lede
country: Belgium
city: Akita
country: Japan
city: Hiroshima
country: Japan
city: Ichikawa
country: Japan
city: Kanzaki
country: Japan
city: Kashihara
country: Japan
city: Kitakyushu
country: Japan
city: Kodaira
country: Japan
city: Kumamoto
country: Japan
city: Nagano
country: Japan
city: Shibukawa
country: Japan
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Perez-Ruixo C, Rossenu S, Zannikos P, Nandy P, Singh J, Drevets WC, Perez-Ruixo JJ. Population Pharmacokinetics of Esketamine Nasal Spray and its Metabolite Noresketamine in Healthy Subjects and Patients with Treatment-Resistant Depression. Clin Pharmacokinet. 2021 Apr;60(4):501-516. doi: 10.1007/s40262-020-00953-4. Epub 2020 Oct 31.
citation: Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, Thase ME, Winokur A, Van Nueten L, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):139-148. doi: 10.1001/jamapsychiatry.2017.3739.