Treatment Resistant Depressive DisorderPhase 2SYNAPSENCT01998958
A Study to Evaluate the Safety and Efficacy of Intranasal Esketamine in Treatment-resistant Depression
A Phase 2 study testing Esketamine 14 mg, Esketamine 28 mg and Esketamine 56 mg in people with Treatment Resistant Depressive Disorder, run by Janssen Research & Development, LLC at 25 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 20 to 64 years
- Conditions the study is for
- Treatment Resistant Depressive Disorder
- What is being tested?
- Esketamine 14 mg, Esketamine 28 mg and Esketamine 56 mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 25 sitesin 3 countries
- Study dates
- 27 Jan 2014to 25 Sep 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- --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
Who cannot join
- -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
Trial locations and contacts
25 sites in 3 countries.
25 sites in 3 countries
United States14 sites
Study site
Allentown, Pennsylvania
Study site
Atlanta, Georgia
Study site
Birmingham, Alabama
Study site
Cedarhurst, New York
Study site
Chicago, Illinois
Study site
Garden Grove, California
Study site
Hartford, Connecticut
Study site
Hoffman Estates, Illinois
Study site
Jacksonville, Florida
Study site
Memphis, Tennessee
Study site
New York, New York
Study site
Philadelphia, Pennsylvania
Study site
Rockville, Maryland
Study site
Tampa, Florida
Japan10 sites
Study site
Akita
Study site
Hiroshima
Study site
Ichikawa
Study site
Kanzaki
Study site
Kashihara
Study site
Kitakyushu
Study site
Kodaira
Study site
Kumamoto
Study site
Nagano
Study site
Shibukawa
About this study
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)
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).
Read the 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.
- Conditions
- Treatment Resistant Depressive Disorder
- Being tested
- Esketamine 14 mg, Esketamine 28 mg, Esketamine 56 mg, Esketamine 84 mg, Placebo
- Keywords
- Treatment resistant depressive disorder, Intranasal esketamine, Efficacy, SYNAPSE, JNJ-54135419
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esketamine 14 mgDrug
1 to 6 sprays of esketamine 14 mg self-administered as an intranasal formulation for 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable during the optional open-label phase for up to 4 days
Esketamine 28 mgDrug
1 to 6 sprays of esketamine 28 mg self-administered as an intranasal formulation for 4 days (Days 1,4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days
Esketamine 56 mgDrug
1 to 6 sprays of esketamine 56 mg self-administered as an intranasal formulation for up to 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days
Esketamine 84 mgDrug
1 to 6 sprays of esketamine 84 mg self-administered as an intranasal formulation for up to 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days
PlaceboDrug
1 to 6 sprays of placebo self-administered as an intranasal formulation for 2 days (Days 1 and 4) or depending on response on Day 8, for 4 days (Days 1,4, 8, 11) during the double-blind phase
| Study group | Role | What they receive |
|---|---|---|
| Esketamine 14 mg | Experimental | Participants in Panel B will self-administer intranasal esketamine 14 milligram or placebo on Days 1, 4, 8, and 11 during the double-blind phase and intranasal esketamine on Days 15, 18, 22, and 25 during the optional open-label phase. During the optional open-label phase, participants will start with treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability). Receives: Drug: Esketamine 14 mg; Drug: Esketamine 56 mg; Drug: Placebo |
| Esketamine 28 mg | Experimental | Participants in Panel A will self-administer intranasal esketamine 28 mg or placebo on Days 1, 4, 8, and 11 during the double-blind phase and intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60, and 74 during the optional open-label phase. During the optional open-label phase, all participants will start treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability). Receives: Drug: Esketamine 28 mg; Drug: Esketamine 56 mg; Drug: Placebo |
| Esketamine 56 mg | Experimental | Participants in Panel A and Panel B will self-administer intranasal esketamine 56 mg or placebo on Days 1, 4, 8, and 11 during the double-blind phase. During the optional open-label phase, participants in Panel A will self-administer intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60, and 74 and participants in Panel B will self-administer intranasal esketamine on Days 15, 18, 22, and 25. During the optional open-label phase, all participants will start treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability). Receives: Drug: Esketamine 56 mg; Drug: Placebo |
| Esketamine 84 mg | Experimental | Participants in Panel A will self-administer intranasal esketamine 84 mg or placebo on Days 1, 4, 8, and 11 during the double-blind phase and intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60, and 74 during the optional open-label phase. During the optional open-label phase, all participants will start treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability). Receives: Drug: Esketamine 56 mg; Drug: Esketamine 84 mg; Drug: Placebo |
| Placebo | Placebo comparator | Participants in Panel A and B will self-administer intranasal placebo on Days 1 and 4 during the double-blind phase. Depending on response on Day 8, participants will receive intranasal placebo on Days 8 and 11 or be re-randomized to receive intranasal placebo or esketamine at a dose of 28 mg, 56 mg, or 84 mg (Panel A) or 14 mg or 56 mg (Panel B) on Day 8 and Day 11. Receives: Drug: Esketamine 14 mg; Drug: Esketamine 28 mg; Drug: Esketamine 56 mg; Drug: Esketamine 84 mg; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. A negative change in score indicates improvement.
Measured: Baseline (Day 1) and Endpoint (Day 8) of Period 1
Panel A and B: Change From Baseline (Day 8) in Montgomery Asberg Depression Rating Scale Total Score at Day 15- ANCOVA Analysis
MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. A negative change in score indicates improvement.
Measured: Baseline (Day 8) and Endpoint (Day 15) of Period 2
Secondary outcomes (14)
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
Sustained response was defined as at least 50% improvement from baseline in the MADRS total score with onset by Day 2 that is maintained to study Day 15. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Measured: Day 2 Up to Day 15
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
Sustained response was defined as at least 50 percent (%) improvement from baseline in the MADRS total score with onset by Day 2 that is maintained to study Day 15. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Measured: Day 2 Up to Day 15
Panel A and B: Percentage of Participants With Response Based on MADRS Total Score
A participant is defined a responder at a given time point if the percent improvement in MADRS is greater than or equal to (>=) 50%. Participant who do not meet such criterion, worsen or discontinue during the DB phase for any reason was considered as non-responders, that is, was assigned a value of 0. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Measured: Period 1: Days 1 (2 hour), 2 and 8 of Double-blind Phase
Panel A and B: Percentage of Participants With Response Based on MADRS Total Score
A participant is defined a responder at a given time point if the percent improvement in MADRS is >=50%. Participant who do not meet such criterion, worsen or discontinue during the DB phase for any reason was considered as non-responders, that is, was assigned a value of 0. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Measured: Period 2: Days 1 (2 hour), 2 and 8 of Double-blind Phase
Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase
Participants who had a MADRS total score of <=10 were considered remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Measured: Days 1, 2 and 8 of Double-blind Phase of Period 1
Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase
Participants who had a MADRS total score of less than or equal to (<=10) were considered remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. A negative change in score indicates improvement.
Measured: Days 1, 2 and 8 of Double-blind Phase of Period 2
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
QIDS-SR16 is self-rated scale assesses severity of depressive symptoms. Total scores range from 0-27. Higher score indicates greater severity of depression. Negative change in score indicates improvement. Total score obtained by adding scores for each of 9 symptom domains of Diagnostic and Statistical Manual of Mental Disorders-4th edition major depressive disorder (DSM-IV MDD) criteria: depressed mood, loss of interest/pleasure, concentration/decision making, self-outlook, suicidal ideation, energy/fatigability, sleep, weight/appetite change, psychomotor changes. 16 items used to rate 9 criterion domains: 4 items used to rate sleep disturbance (early/middle/late insomnia/hypersomnia); 2 items used to rate psychomotor disturbance (agitation, retardation); 4 items used to rate appetite/weight disturbance. 1 item used to rate 6 domains (depressed mood, decreased interest, decreased energy, worthlessness/guilt, concentration/decision making, suicidal ideation). Each item was rated 0-3.
Measured: Baseline (Day 1) and Endpoint (Day 8) of Period 1
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
QIDS-SR16 is self-rated scale assesses severity of depressive symptoms. Total scores range from 0-27. Higher score indicates greater severity of depression. Negative change in score indicates improvement. Total score obtained by adding scores for each of 9 symptom domains of Diagnostic and Statistical Manual of Mental Disorders-4th edition major depressive disorder (DSM-IV MDD) criteria: depressed mood, loss of interest/pleasure, concentration/decision making, self-outlook, suicidal ideation, energy/fatigability, sleep, weight/appetite change, psychomotor changes. 16 items used to rate 9 criterion domains: 4 items used to rate sleep disturbance (early/middle/late insomnia/hypersomnia); 2 items used to rate psychomotor disturbance (agitation, retardation); 4 items used to rate appetite/weight disturbance. 1 item used to rate 6 domains (depressed mood, decreased interest, decreased energy, worthlessness/guilt, concentration/decision making, suicidal ideation). Each item was rated 0-3.
Measured: Baseline (Day 8) and Endpoint (Day 15) of Period 2
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
CGI-S provides measure of severity of participant's illness including participant's history, psychosocial circumstances, symptoms, behavior and impact of symptoms on ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Considering total clinical experience, participant is assessed on severity of mental illness according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill patients. CGI-S permits global evaluation of participant's condition at given time. A negative change in score indicates improvement.
Measured: Baseline (Day 1) and Endpoint (Day 8) of Period 1
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
CGI-S provides measure of severity of participant's illness including participant's history, psychosocial circumstances, symptoms, behavior and impact of symptoms on ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Considering total clinical experience, participant is assessed on severity of mental illness according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill patients. CGI-S permits global evaluation of participant's condition at given time. A negative change in score indicates improvement.
Measured: Baseline (Day 8) and Endpoint (Day 15) of Period 2
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
GAD-7 is a brief and validated 7-item self-report assessment of overall anxiety. Participants respond to each item using a 4-point scale with response categories of 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield a total score with a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15 -21).
Measured: Baseline (Day 1) and Endpoint (Day 8) of Period 1
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
GAD-7 is a brief and validated 7-item self-report assessment of overall anxiety. Participants respond to each item using a 4-point scale with response categories of 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield a total score with a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15 -21).
Measured: Baseline (Day 8) and Endpoint (Day 15) of Period 2
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
PGI-S is a patient-rated scale that assesses the severity of their illness at the time of assessment, relative to participants past experience. It is a 4-point (1 to 4) scale in response to the question 'Considering all aspects of your depression right now would you say your depression is?' with scores as follows: 1: none; 2: mild; 3: moderate; 4: severe. A higher score implies a more severe condition.
Measured: Baseline (Day 1) and Endpoint (Day 8) of Period 1
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
PGI-S is a patient-rated scale that assesses the severity of their illness at the time of assessment, relative to participants past experience. It is a 4-point (1 to 4) scale in response to the question 'Considering all aspects of your depression right now would you say your depression is?' with scores as follows: 1: none; 2: mild; 3: moderate; 4: severe. A higher score implies a more severe condition. A negative change in score indicates improvement.
Measured: Baseline (Day 8) and Endpoint (Day 15) of Period 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2013 (estimated)
- Study start27 Jan 2014
- Primary completion21 Jul 2015
- Study completion25 Sep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01998958
- Sponsor's protocol ID
- CR102968
- Other IDs
- 2013-004005-11, JNJ-54135419, ESKETINTRD2003
- Acronym
- SYNAPSE
- Status last verified
- Apr 2025
- First submitted
- 25 Nov 2013
- Last updated
- 29 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
Publications
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.
PubMed 33128208Daly 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.
PubMed 29282469
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01998958
- Acronym / sponsor ID
- SYNAPSE / CR102968
- Conditions
- Treatment Resistant Depressive Disorder
- Keywords
- Treatment resistant depressive disorder, Intranasal esketamine, Efficacy, SYNAPSE, JNJ-54135419
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 27 Jan 2014 (actual)
- Primary completion
- 21 Jul 2015 (actual)
- Study completion
- 25 Sep 2015 (actual)
- First posted
- 3 Dec 2013 (estimated)
- Results
- Posted 12 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Esketamine 14 mg | Experimental | Drug: Esketamine 14 mg, Drug: Esketamine 56 mg, Drug: PlaceboParticipants in Panel B will self-administer intranasal esketamine 14 milligram or placebo on Days 1, 4, 8, and 11 during the double-blind phase and intranasal esketamine on Days 15, 18, 22, and 25 during the optional open-label phase. During the optional open-label phase, participants will start with treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability). |
| Esketamine 28 mg | Experimental | Drug: Esketamine 28 mg, Drug: Esketamine 56 mg, Drug: PlaceboParticipants in Panel A will self-administer intranasal esketamine 28 mg or placebo on Days 1, 4, 8, and 11 during the double-blind phase and intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60, and 74 during the optional open-label phase. During the optional open-label phase, all participants will start treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability). |
| Esketamine 56 mg | Experimental | Drug: Esketamine 56 mg, Drug: PlaceboParticipants in Panel A and Panel B will self-administer intranasal esketamine 56 mg or placebo on Days 1, 4, 8, and 11 during the double-blind phase. During the optional open-label phase, participants in Panel A will self-administer intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60, and 74 and participants in Panel B will self-administer intranasal esketamine on Days 15, 18, 22, and 25. During the optional open-label phase, all participants will start treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability). |
| Esketamine 84 mg | Experimental | Drug: Esketamine 56 mg, Drug: Esketamine 84 mg, Drug: PlaceboParticipants in Panel A will self-administer intranasal esketamine 84 mg or placebo on Days 1, 4, 8, and 11 during the double-blind phase and intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60, and 74 during the optional open-label phase. During the optional open-label phase, all participants will start treatment with a 56-mg dose of intranasal esketamine on Day 15 (the dose of esketamine can be adjusted if desired based on the Investigator's clinical judgment of efficacy and tolerability). |
| Placebo | Placebo comparator | Drug: Esketamine 14 mg, Drug: Esketamine 28 mg, Drug: Esketamine 56 mg, Drug: Esketamine 84 mg, Drug: PlaceboParticipants in Panel A and B will self-administer intranasal placebo on Days 1 and 4 during the double-blind phase. Depending on response on Day 8, participants will receive intranasal placebo on Days 8 and 11 or be re-randomized to receive intranasal placebo or esketamine at a dose of 28 mg, 56 mg, or 84 mg (Panel A) or 14 mg or 56 mg (Panel B) on Day 8 and Day 11. |
Who may qualify
- Ages
- 20 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- --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
Key exclusion criteria (1 listed)
- -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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Esketamine 14 mg1 to 6 sprays of esketamine 14 mg self-administered as an intranasal formulation for 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable during the optional open-label phase for up to 4 days | Drug | Esketamine 14 mg, Placebo |
| Esketamine 28 mg1 to 6 sprays of esketamine 28 mg self-administered as an intranasal formulation for 4 days (Days 1,4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days | Drug | Esketamine 28 mg, Placebo |
| Esketamine 56 mg1 to 6 sprays of esketamine 56 mg self-administered as an intranasal formulation for up to 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days | Drug | Esketamine 14 mg, Esketamine 28 mg, Esketamine 56 mg, Esketamine 84 mg, Placebo |
| Esketamine 84 mg1 to 6 sprays of esketamine 84 mg self-administered as an intranasal formulation for up to 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days | Drug | Esketamine 84 mg, Placebo |
| Placebo1 to 6 sprays of placebo self-administered as an intranasal formulation for 2 days (Days 1 and 4) or depending on response on Day 8, for 4 days (Days 1,4, 8, 11) during the double-blind phase | Drug | Esketamine 14 mg, Esketamine 28 mg, Esketamine 56 mg, Esketamine 84 mg, Placebo |
Primary outcome
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
Time frame: Baseline (Day 1) and Endpoint (Day 8) of Period 1
MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. A negative change in score indicates improvement.
Panel A and B: Change From Baseline (Day 8) in Montgomery Asberg Depression Rating Scale Total Score at Day 15- ANCOVA Analysis
Time frame: Baseline (Day 8) and Endpoint (Day 15) of Period 2
MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. A negative change in score indicates improvement.
14 secondary outcomes
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
Time frame: Day 2 Up to Day 15
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
Time frame: Day 2 Up to Day 15
Panel A and B: Percentage of Participants With Response Based on MADRS Total Score
Time frame: Period 1: Days 1 (2 hour), 2 and 8 of Double-blind Phase
Panel A and B: Percentage of Participants With Response Based on MADRS Total Score
Time frame: Period 2: Days 1 (2 hour), 2 and 8 of Double-blind Phase
Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase
Time frame: Days 1, 2 and 8 of Double-blind Phase of Period 1
Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase
Time frame: Days 1, 2 and 8 of Double-blind Phase of Period 2
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
Time frame: Baseline (Day 1) and Endpoint (Day 8) of Period 1
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
Time frame: Baseline (Day 8) and Endpoint (Day 15) of Period 2
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
Time frame: Baseline (Day 1) and Endpoint (Day 8) of Period 1
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
Time frame: Baseline (Day 8) and Endpoint (Day 15) of Period 2
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
Time frame: Baseline (Day 1) and Endpoint (Day 8) of Period 1
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
Time frame: Baseline (Day 8) and Endpoint (Day 15) of Period 2
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
Time frame: Baseline (Day 1) and Endpoint (Day 8) of Period 1
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
Time frame: Baseline (Day 8) and Endpoint (Day 15) of Period 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33128208Perez-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.
- Derived from this study: PubMed 29282469Daly 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.
- A Double-Blind, Doubly-Randomized, Placebo-Controlled Study of Intranasal Esketamine in an Adaptive Treatment Protocol to Assess Safety and Efficacy in Treatment-Resistant DepressionLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
25 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Esketamine 14 mg, Esketamine 28 mg and Esketamine 56 mg in people with Treatment Resistant Depressive Disorder, run by Janssen Research & Development, LLC at 25 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Japan, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Baseline (Day 1) and Endpoint (Day 8) of Period 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01998958, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.