SYNAPSE: A Study to Evaluate the Safety and Efficacy of Intranasal Esketamine in Treatment-resistant Depression
Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01998958
Collaborator
(none)
108
25
5
19.9
4.3
0.2
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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
Study Type:
Interventional
Actual Enrollment
:
108 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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)
Actual Study Start Date
:
Jan 27, 2014
Actual Primary Completion Date
:
Jul 21, 2015
Actual Study Completion Date
:
Sep 25, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Esketamine 14 mg 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). |
Drug: Esketamine 14 mg
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
Drug: Esketamine 56 mg
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
Drug: Placebo
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
|
| Experimental: Esketamine 28 mg 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). |
Drug: Esketamine 28 mg
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
Drug: Esketamine 56 mg
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
Drug: Placebo
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
|
| Experimental: Esketamine 56 mg 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). |
Drug: Esketamine 56 mg
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
Drug: Placebo
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
|
| Experimental: Esketamine 84 mg 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). |
Drug: Esketamine 56 mg
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
Drug: Esketamine 84 mg
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
Drug: Placebo
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
|
| Placebo Comparator: Placebo 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. |
Drug: Esketamine 14 mg
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
Drug: Esketamine 28 mg
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
Drug: Esketamine 56 mg
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
Drug: Esketamine 84 mg
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
Drug: Placebo
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
|
Outcome Measures
Primary Outcome Measures
- 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 [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 [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.
Secondary Outcome Measures
- 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 [Day 2 Up to Day 15]
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.
- 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 [Day 2 Up to Day 15]
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.
- Panel A and B: Percentage of Participants With Response Based on MADRS Total Score [Period 1: Days 1 (2 hour), 2 and 8 of Double-blind Phase]
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.
- Panel A and B: Percentage of Participants With Response Based on MADRS Total Score [Period 2: Days 1 (2 hour), 2 and 8 of Double-blind Phase]
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.
- Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase [Days 1, 2 and 8 of Double-blind Phase of Period 1]
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.
- Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase [Days 1, 2 and 8 of Double-blind Phase of Period 2]
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.
- 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 [Baseline (Day 1) and Endpoint (Day 8) of Period 1]
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.
- 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 [Baseline (Day 8) and Endpoint (Day 15) of Period 2]
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.
- 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 [Baseline (Day 1) and Endpoint (Day 8) of Period 1]
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.
- 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 [Baseline (Day 8) and Endpoint (Day 15) of Period 2]
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.
- 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 [Baseline (Day 1) and Endpoint (Day 8) of Period 1]
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).
- 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 [Baseline (Day 8) and Endpoint (Day 15) of Period 2]
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).
- 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 [Baseline (Day 1) and Endpoint (Day 8) of Period 1]
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.
- 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 [Baseline (Day 8) and Endpoint (Day 15) of Period 2]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
to 64 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | ||
| 2 | Garden Grove | California | United States | ||
| 3 | Hartford | Connecticut | United States | ||
| 4 | Jacksonville | Florida | United States | ||
| 5 | Tampa | Florida | United States | ||
| 6 | Atlanta | Georgia | United States | ||
| 7 | Chicago | Illinois | United States | ||
| 8 | Hoffman Estates | Illinois | United States | ||
| 9 | Rockville | Maryland | United States | ||
| 10 | Cedarhurst | New York | United States | ||
| 11 | New York | New York | United States | ||
| 12 | Allentown | Pennsylvania | United States | ||
| 13 | Philadelphia | Pennsylvania | United States | ||
| 14 | Memphis | Tennessee | United States | ||
| 15 | Lede | Belgium | |||
| 16 | Akita | Japan | |||
| 17 | Hiroshima | Japan | |||
| 18 | Ichikawa | Japan | |||
| 19 | Kanzaki | Japan | |||
| 20 | Kashihara | Japan | |||
| 21 | Kitakyushu | Japan | |||
| 22 | Kodaira | Japan | |||
| 23 | Kumamoto | Japan | |||
| 24 | Nagano | Japan | |||
| 25 | Shibukawa | Japan |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01998958
Other Study ID Numbers:
- CR102968
- 2013-004005-11
- JNJ-54135419
- ESKETINTRD2003
First Posted:
Dec 3, 2013
Last Update Posted:
Jun 2, 2020
Last Verified:
May 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Keywords provided by Janssen Research & Development, LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo (Panel A: Period 1) | Esketamine 28 mg (Panel A: Period 1) | Esketamine 56 mg (Panel A: Period 1) | Esketamine 84 mg (Panel A: Period 1) | Placebo (Panel B: Period 1) | Esketamine 14 mg (Panel B: Period 1) | Esketamine 56 mg (Panel B: Period 1) | Placebo (Panel A: Period 2) QIDS >= 11 Participants | Placebo (Panel A: Period 2) QIDS<11 Participants | Placebo to Esketamine 28mg (Panel A: Period 2) | Placebo to Esketamine 56 mg (Panel A: Period 2) | Placebo to Esketamine 84 mg (Panel A: Period 2) | Esketamine 28 mg (Panel A: Period 2) | Esketamine 56 mg (Panel A: Period 2) | Esketamine 84 mg (Panel A: Period 2) | Placebo (Panel B: Period 2) QIDS >=11 Participants | Placebo (Panel B: Period 2) QIDS<11 Participants | Placebo to Esketamine 14mg (Panel B: Period 2) | Placebo to Esketamine 56mg (Panel B: Period 2) | Esketamine 14 mg (Panel B: Period 2) | Esketamine 56 mg (Panel B: Period 2) | Placebo/Placebo/Open Label Esketamine (Panel A) | Placebo/Esketamine/Open Label Esketamine (Panel A) | Esketamine/Esketamine/Open Label Esketamine (Panel A) | Placebo/Placebo/Open Label Esketamine (Panel B) | Placebo/Esketamine/Open Label Esketamine (Panel B) | Esketamine/Esketamine/Open Label Esketamine (Panel B) | Placebo: Follow up Phase | Esketamine 14 mg: Follow up Phase | Esketamine 28 mg: Follow up Phase | Esketamine 56 mg: Follow up Phase | Esketamine 84 mg: Follow up Phase |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants self-administered placebo intranasally (1 spray to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1 in Panel A. | Participants self administered esketamine 28 milligram (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 1 and 4 of Period 1 in Panel A. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 1 and 4 of Period 1 in Panel A. | Participants self administered esketamine 84 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1 in Panel A. | Participants self administered placebo intranasally (1 spray to each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1 in Panel B. | Participants self administered esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) on Days 1 and 4 of Period 1 in Panel B. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1 in Panel B. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score greater than or equal to [>=] 11) were re-randomized to receive Placebo (1 spray to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were responders (with QIDS-SR16 score <11) at the end of Period 1 in Panel A continued to receive placebo (1 spray to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were re-randomized to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were re-randomized to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were re-randomized to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who received esketamine 28 mg in Period 1 of Panel A continued to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who received esketamine 56 mg in Period 1 of Panel A continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2. | Participants who received esketamine 84 mg in Period 1 of Panel A continued to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders with QIDS-SR16 score >=11 at the end of Period 1 were re-randomized to receive placebo intranasally (1 spray of placebo into each nostril at 0 and 5 minutes using 4 separate devices) on Days 8 and 11 of Period 2 in Panel B. | Participants who were responders with QIDS-SR16 score <11 at the end of Period 1 continued to receive placebo intranasally (1 spray of placebo into each nostril at 0 and 5 minutes using 4 separate devices) on Days 8 and 11 in Period 2. | Participants who received placebo in Period 1 and were non-responders with QIDS-SR16 score >=11 at the end of Period 1 were re-randomized to receive esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo in other nostril at 0 minute and 1 spray of placebo in each nostril at 5 minutes using 4 separate devices) on Days 8 and 11 in Period 2. | Participants who received placebo in Period 1 and were non-responders (with QIDS-SR16 score >=11) at the end of Period 1 in Panel B were re-randomized to receive esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2. | Participants who received esketamine 14 mg in Period 1 of Panel B continued to receive esketamine 14 mg (1 spray of esketamine 14 mg to one nostril and 1 spray of placebo into other nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 in Period 2. | Participants who received esketamine 56 mg in Period 1 of Panel B continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2. | Participants who received Placebo in Period 1 and 2 of Panel A and elected to continue with open label phase received up to 9 single doses of intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60 and 74. The doses for the optional open-label treatment phase included 28, 56, and 84 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18, 22, 25, 32, 39, and 46 could be adjusted to the next lower or higher dose, based on the investigator's clinical judgment. The same dose administered on Day 46 was administered on Day 60 and Day 74. | Participants who received Placebo in Period 1 and esketamine in Period 2 of Panel A and elected to continue with open label phase received up to 9 single doses of intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60 and 74. The doses for the optional open-label treatment phase included 28, 56, and 84 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18, 22, 25, 32, 39, and 46 could be adjusted to the next lower or higher dose, based on the investigator's clinical judgment. The same dose administered on Day 46 was administered on Day 60 and Day 74. | Participants who received esketamine in Period 1 and 2 of Panel A and elected to continue with open label phase received up to 9 single doses of intranasal esketamine on Days 15, 18, 22, 25, 32, 39, 46, 60 and 74. The doses for the optional open-label treatment phase included 28, 56, and 84 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18, 22, 25, 32, 39, and 46 could be adjusted to the next lower or higher dose, based on the investigator's clinical judgment. The same dose administered on Day 46 was administered on Day 60 and Day 74. | Participants who received Placebo in Period 1 and 2 of Panel A and elected to continue with open label phase received up to 4 single doses of intranasal esketamine on Days 15, 18, 22 and 25. The doses for the optional open-label treatment phase included 14, 28 and 56 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18, 22 and 25 could be adjusted to the next lower or higher dose, based on the investigator's clinical judgment. | Participants who received Placebo in Period 1 and esketamine in Period 2 of Panel A and elected to continue with open label phase received up to 4 single doses of intranasal esketamine on Days 15, 18, 22 and 25. The doses for the optional open-label treatment phase included 14, 28 and 56 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18, 22 and 25 could be adjusted to the next lower or higher dose, based on the investigator's clinical judgment. | Participants who received esketamine in Period 1 and 2 of Panel A and elected to continue with open label phase received up to 4 single doses of intranasal esketamine on Days 15, 18, 22 and 25. The doses for the optional open-label treatment phase included 14, 28 and 56 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18, 22 and 25 could be adjusted to the next lower or higher dose, based on the investigator's clinical judgment. | All participants whose last dose was Placebo in the double-blind phase or open label phase and were not consent withdrawn were followed for safety for 8 weeks. | All participants whose last dose was esketamine 14 mg in the double-blind phase or open label phase and were not consent withdrawn were followed for safety for 8 weeks. | All participants whose last dose was esketamine 28 mg in the double-blind phase or open label phase and were not consent withdrawn were followed for safety for 8 weeks. | All participants whose last dose was esketamine 56 mg in the double-blind phase or open label phase and were not consent withdrawn were followed for safety for 8 weeks. | All participants whose last dose was esketamine 84 mg in the double-blind phase or open label phase and were not consent withdrawn were followed for safety for 8 weeks. |
| Period Title: Period 1 (Panel A and B) | ||||||||||||||||||||||||||||||||
| STARTED | 33 | 11 | 11 | 12 | 21 | 11 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Rerandomized to Esketamine 56 mg | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Rerandomized to Esketamine 28mg | 8 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Rerandomized to Esketamine 84mg | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 32 | 8 | 11 | 12 | 21 | 11 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Period 1 (Panel A and B) | ||||||||||||||||||||||||||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 4 | 8 | 9 | 5 | 8 | 11 | 12 | 5 | 8 | 5 | 3 | 11 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 4 | 8 | 8 | 5 | 8 | 11 | 10 | 5 | 8 | 5 | 2 | 11 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Period 1 (Panel A and B) | ||||||||||||||||||||||||||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 10 | 20 | 27 | 13 | 7 | 19 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 11 | 23 | 13 | 7 | 19 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 9 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Period 1 (Panel A and B) | ||||||||||||||||||||||||||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 4 | 12 | 39 | 42 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 4 | 12 | 39 | 42 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo (Panel A: Period 1) | Esketamine 28 mg (Panel A: Period 1) | Esketamine 56 mg (Panel A: Period 1) | Esketamine 84 mg (Panel A: Period 1) | Placebo (Panel B: Period 1) | Esketamine 14 mg (Panel B: Period 1) | Esketamine 56 mg (Panel B: Period 1) | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants self-administered placebo intranasally (1 spray to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1 in Panel A. | Participants self administered esketamine 28 milligram (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 1 and 4 of Period 1 in Panel A. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 1 and 4 of Period 1 in Panel A. | Participants self administered esketamine 84 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1 in Panel A. | Participants self administered placebo intranasally (1 spray to each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1 in Panel B. | Participants self administered esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) on Days 1 and 4 of Period 1 in Panel B. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1 in Panel B. | Total of all reporting groups |
| Overall Participants | 33 | 11 | 11 | 12 | 21 | 11 | 9 | 108 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [years] |
44.4
(9.60)
|
42.1
(10.31)
|
42.7
(11.23)
|
49.8
(9.29)
|
45.3
(7.66)
|
42.2
(9.43)
|
45.6
(7.35)
|
44.6
(9.29)
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
18
54.5%
|
5
45.5%
|
9
81.8%
|
6
50%
|
9
42.9%
|
4
36.4%
|
4
44.4%
|
55
50.9%
|
| Male |
15
45.5%
|
6
54.5%
|
2
18.2%
|
6
50%
|
12
57.1%
|
7
63.6%
|
5
55.6%
|
53
49.1%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.9%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
21
100%
|
11
100%
|
9
100%
|
41
38%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
9
27.3%
|
4
36.4%
|
4
36.4%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
18
16.7%
|
| White |
24
72.7%
|
7
63.6%
|
6
54.5%
|
11
91.7%
|
0
0%
|
0
0%
|
0
0%
|
48
44.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 1) and Endpoint (Day 8) of Period 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 1 Intent-to-treat (ITT) analysis set included all participants randomly assigned to treatment in period 1. |
| Arm/Group Title | Panel A: Period 1 Placebo | Panel A: Period 1 Esketamine 28 mg | Panel A: Period 1 Esketamine 56 mg | Panel A: Period 1 Esketamine 84 mg | Panel B: Period 1 Placebo | Panel B: Period 1 Esketamine 14 mg | Panel B: Period 1 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants self administered placebo intranasally (1 spray to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 28 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 84 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered placebo intranasally (1 spray to each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. |
| Measure Participants | 33 | 11 | 11 | 12 | 21 | 11 | 9 |
| Least Squares Mean (Standard Error) [Unit on a scale] |
-4.9
(1.74)
|
-9.8
(2.72)
|
-12.4
(2.66)
|
-15.3
(2.56)
|
-6.6
(1.53)
|
-4.8
(2.13)
|
-10.3
(2.36)
|
| Title | Panel A and B: Change From Baseline (Day 8) in Montgomery Asberg Depression Rating Scale Total Score at Day 15- ANCOVA Analysis |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 8) and Endpoint (Day 15) of Period 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 2 ITT analysis set included non-responders (QIDS-SR16 total score >=11) to placebo treatment in Period 1 and were then randomly re-assigned to a treatment group in Period 2. Only placebo participants with a QIDS-SR16 score >= 11 at End Point Period 1 who were re-randomized in Period 2 are included in the Period 2 summary. |
| Arm/Group Title | Panel A: Period 2 Placebo | Panel A:Period 2 Esketamine 28 mg | Panel A: Period 2 Esketamine 56 mg | Panel A: Period 2 Esketamine 84 mg | Panel B: Period 2 Placebo | Panel B: Period 2 Esketamine 14 mg | Panel B:Period 2 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who were non-responders at the end of Period 1 in Panel A (with Quick Inventory of Depressive Symptomatology - 16-item Self Report (QIDS-SR16) score >=11) were randomly re-assigned to receive same Placebo (1 spray to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly re-assigned to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders with QIDS-SR 16 score >=11 received placebo intranasally (1 spray of placebo into each nostril at 0 and 5 minutes) on Days 8 and 11 of Period 2. | Participants who received placebo in Period 1 and were non-responders with QIDS-SR16 score >=11 received esketamine 14 mg intranasally (1 spray of esketamine into one nostril and 1 spray of placebo in other nostril at 0 minutes and 1 spray of placebo in each nostril at 5 minutes) in Period 2. | Participants who were responders (with QIDS-SR16 score <11) at the end of Period 1 in Panel B continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2. |
| Measure Participants | 6 | 8 | 9 | 5 | 5 | 5 | 3 |
| Least Squares Mean (Standard Error) [Unit on a scale] |
-4.5
(2.92)
|
-7.6
(2.49)
|
-8.9
(2.51)
|
-11.4
(2.68)
|
-0.7
(3.32)
|
-6.6
(4.02)
|
-1.2
(6.04)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Day 2 Up to Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population analyzed included participants from double-blind (DB) ITT (who were randomly assigned to treatment during the double-blind phase) who completed the double-blind phase and received the same treatment for both periods. |
| Arm/Group Title | Panel A: Placebo (Period 1 and 2) | Panel A: Esketamine 28 mg (Period 1 and 2) | Panel A: Esketamine 56 mg (Period 1 and 2) | Panel A: Esketamine 84 mg (Period 1 and 2) | Panel B: Placebo (Period 1 and 2) | Panel B: Esketamine 14 mg (Period 1 and 2) | Panel B: Esketamine 56 mg (Period 1 and 2) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who received same placebo (1 spray to each nostril at 0, 5 and 10 minutes) treatment in Period 1 and 2 of Panel A. | Participants who received same esketamine 28mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) treatment in Period 1 and 2 of Panel A. | Participants who received same esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) treatment in Period 1 and 2 of Panel A. | Participants who received same esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) treatment in Period 1 and 2 of Panel A. | Participants who received same placebo (1 spray to each nostril at 0 and 5 minutes) treatment in Period 1 and 2 of Panel B. | Participants who received same esketamine 14 mg (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) treatment in Period 1 and 2 of Panel B. | Participants who received same esketamine 56 mg (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) treatment in Period 1 and 2 of Panel B. |
| Measure Participants | 10 | 8 | 11 | 10 | 13 | 11 | 9 |
| Number [Percentage of participants] |
0
0%
|
12.5
113.6%
|
9.1
82.7%
|
30.0
250%
|
15.4
73.3%
|
18.2
165.5%
|
22.2
246.7%
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Day 2 Up to Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population analyzed included participants from DB ITT (who were randomly assigned to treatment during the double-blind phase) who received the same treatment for both periods, including participants who did not complete the double-blind Phase. |
| Arm/Group Title | Panel A: Placebo (Period 1 and 2) | Panel A: Esketamine 28 mg (Period 1 and 2) | Panel A: Esketamine 56 mg (Period 1 and 2) | Panel A: Esketamine 84 mg (Period 1 and 2) | Panel B: Placebo (Period 1 and 2) | Panel B: Esketamine 14 mg (Period 1 and 2) | Panel B: Esketamine 56 mg (Period 1 and 2) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who received same placebo (1 spray to each nostril at 0, 5 and 10 minutes) treatment in Period 1 and 2 of Panel A. | Participants who received same esketamine 28mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) treatment in Period 1 and 2 of Panel A. | Participants who received same esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) treatment in Period 1 and 2 of Panel A. | Participants who received same esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) treatment in Period 1 and 2 of Panel A. | Participants who received same placebo (1 spray to each nostril at 0 and 5 minutes) treatment in Period 1 and 2 of Panel B. | Participants who received same esketamine 14 mg (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) treatment in Period 1 and 2 of Panel B. | Participants who received same esketamine 56 mg (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) treatment in Period 1 and 2 of Panel B. |
| Measure Participants | 10 | 8 | 11 | 12 | 13 | 11 | 9 |
| Number [Percentage of participants] |
0
0%
|
12.5
113.6%
|
9.1
82.7%
|
25.0
208.3%
|
15.4
73.3%
|
18.2
165.5%
|
22.2
246.7%
|
| Title | Panel A and B: Percentage of Participants With Response Based on MADRS Total Score |
|---|---|
| Description | 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. |
| Time Frame | Period 1: Days 1 (2 hour), 2 and 8 of Double-blind Phase |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 1 ITT analysis set included all participants randomly assigned to treatment in period 1. |
| Arm/Group Title | Panel A: Period 1 Placebo | Panel A: Period 1 Esketamine 28 mg | Panel A: Period 1 Esketamine 56 mg | Panel A: Period 1 Esketamine 84 mg | Panel B: Period 1 Placebo | Panel B: Period 1 Esketamine 14 mg | Panel B: Period 1 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants self administered placebo intranasally (1 spray to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 28 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 84 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered placebo intranasally (1 spray to each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. |
| Measure Participants | 33 | 11 | 11 | 12 | 21 | 11 | 9 |
| Day 1 (2 hour) |
18.2
55.2%
|
54.5
495.5%
|
36.4
330.9%
|
58.3
485.8%
|
33.3
158.6%
|
36.4
330.9%
|
44.4
493.3%
|
| Day 2 |
3.0
9.1%
|
36.4
330.9%
|
27.3
248.2%
|
41.7
347.5%
|
28.6
136.2%
|
36.4
330.9%
|
44.4
493.3%
|
| Day 8 |
6.1
18.5%
|
9.1
82.7%
|
18.2
165.5%
|
41.7
347.5%
|
23.8
113.3%
|
18.2
165.5%
|
22.2
246.7%
|
| Title | Panel A and B: Percentage of Participants With Response Based on MADRS Total Score |
|---|---|
| Description | 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. |
| Time Frame | Period 2: Days 1 (2 hour), 2 and 8 of Double-blind Phase |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 2 ITT analysis set included non-responders (QIDS-SR16 total score >=11) to placebo treatment in Period 1 and were then randomly re-assigned to a treatment group in Period 2. Only placebo participants with a QIDS-SR16 score >= 11 at End Point Period 1 who were re-randomized in Period 2 are included in the Period 2 summary. |
| Arm/Group Title | Panel A: Period 2 Placebo | Panel A: Period 2 Esketamine 28 mg | Panel A: Period 2 Esketamine 56 mg | Panel A: Period 2 Esketamine 84 mg | Panel B: Period 2 Placebo | Panel B: Period 2 Esketamine 14 mg | Panel B: Period 2 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who were non-responders at the end of Period 1 in Panel A (with Quick Inventory of Depressive Symptomatology - 16-item Self Report (QIDS-SR16) score >=11) were randomly re-assigned to receive same Placebo (1 spray to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly re-assigned to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders with QIDS-SR 16 score >=11 received placebo intranasally (1 spray of placebo into each nostril at 0 and 5 minutes) on Days 8 and 11 of Period 2. | Participants who received placebo in Period 1 and were non-responders with QIDS-SR16 score >=11 received esketamine 14 mg intranasally (1 spray of esketamine into one nostril and 1 spray of placebo in other nostril at 0 minutes and 1 spray of placebo in each nostril at 5 minutes) in Period 2. | Participants who were responders (with QIDS-SR16 score <11) at the end of Period 1 in Panel B continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2. |
| Measure Participants | 6 | 8 | 9 | 5 | 5 | 5 | 3 |
| Day 1 (2 hour) |
16.7
50.6%
|
12.5
113.6%
|
22.2
201.8%
|
40.0
333.3%
|
0
0%
|
60.0
545.5%
|
0
0%
|
| Day 2 |
0
0%
|
0
0%
|
11.1
100.9%
|
40.0
333.3%
|
0
0%
|
80.0
727.3%
|
0
0%
|
| Day 8 |
0
0%
|
12.5
113.6%
|
0
0%
|
20.0
166.7%
|
0
0%
|
0
0%
|
33.3
370%
|
| Title | Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 2 and 8 of Double-blind Phase of Period 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 1 ITT analysis set included all participants randomly assigned to treatment in period 1. |
| Arm/Group Title | Panel A: Period 1: Placebo | Panel A: Period 1 Esketamine 28 mg | Panel A: Period 1: Esketamine 56 mg | Panel A: Period 1 Esketamine 84 mg | Panel B: Period 1 Placebo | Panel B: Period 1 Esketamine 14 mg | Panel B: Period 1 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants self administered placebo intranasally (1 spray to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 28 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 84 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered placebo intranasally (1 spray to each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. |
| Measure Participants | 33 | 11 | 11 | 12 | 21 | 11 | 9 |
| Day 1 |
3.0
9.1%
|
27.3
248.2%
|
18.2
165.5%
|
25.0
208.3%
|
19.0
90.5%
|
36.4
330.9%
|
33.3
370%
|
| Day 2 |
0
0%
|
36.4
330.9%
|
18.2
165.5%
|
25.0
208.3%
|
19.0
90.5%
|
27.3
248.2%
|
33.3
370%
|
| Day 8 |
3.0
9.1%
|
9.1
82.7%
|
9.1
82.7%
|
25.0
208.3%
|
14.3
68.1%
|
18.2
165.5%
|
22.2
246.7%
|
| Title | Panel A and B: Percentage of Participants in Remission Based on MADRS Total Score at Days 1, 2 and 8 of Double-blind Phase |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 2 and 8 of Double-blind Phase of Period 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 2 ITT analysis set included non-responders (QIDS-SR16 total score >=11) to placebo treatment in Period 1 and were then randomly re-assigned to a treatment group in Period 2. Only placebo participants with a QIDS-SR16 score >= 11 at End Point Period 1 who were re-randomized in Period 2 are included in the Period 2 summary. |
| Arm/Group Title | Panel A: Period 2 Placebo | Panel A: Period 2 Esketamine 28 mg | Panel A: Period 2 Esketamine 56 mg | Panel A: Period 2 Esketamine 84 mg | Panel B: Period 2 Placebo | Panel B: Period 2 Esketamine 14 mg | Panel B: Period 2 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who were non-responders at the end of Period 1 in Panel A (with Quick Inventory of Depressive Symptomatology - 16-item Self Report (QIDS-SR16) score >=11) were randomly re-assigned to receive same Placebo (1 spray to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly re-assigned to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders with QIDS-SR 16 score >=11 received placebo intranasally (1 spray of placebo into each nostril at 0 and 5 minutes) on Days 8 and 11 of Period 2. | Participants who received placebo in Period 1 and were non-responders with QIDS-SR16 score >=11 received esketamine 14 mg intranasally (1 spray of esketamine into one nostril and 1 spray of placebo in other nostril at 0 minutes and 1 spray of placebo in each nostril at 5 minutes) in Period 2. | Participants who were responders (with QIDS-SR16 score <11) at the end of Period 1 in Panel B continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2. |
| Measure Participants | 6 | 8 | 9 | 5 | 5 | 5 | 3 |
| Day 1 |
16.7
50.6%
|
12.5
113.6%
|
0
0%
|
40.0
333.3%
|
0
0%
|
60.0
545.5%
|
0
0%
|
| Day 2 |
0
0%
|
0
0%
|
0
0%
|
20.0
166.7%
|
0
0%
|
80.0
727.3%
|
0
0%
|
| Day 8 |
0
0%
|
12.5
113.6%
|
0
0%
|
20.0
166.7%
|
0
0%
|
0
0%
|
0
0%
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 1) and Endpoint (Day 8) of Period 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 1 ITT analysis set included all participants randomly assigned to treatment in period 1. |
| Arm/Group Title | Panel A: Period 1 Placebo | Panel A: Period 1 Esketamine 28 mg | Panel A: Period 1 Esketamine 56 mg | Panel A: Period 1 Esketamine 84 mg | Panel B: Period 1 Placebo | Panel B: Period 1 Esketamine 14 mg | Panel B: Period 1 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants self administered placebo intranasally (1 spray to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 28 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 84 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered placebo intranasally (1 spray to each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. |
| Measure Participants | 33 | 11 | 11 | 12 | 21 | 11 | 9 |
| Least Squares Mean (Standard Error) [Unit on a scale] |
-1.8
(0.93)
|
-4.0
(1.43)
|
-4.4
(1.43)
|
-4.2
(1.39)
|
-1.1
(0.78)
|
-0.6
(1.10)
|
-3.0
(1.20)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 8) and Endpoint (Day 15) of Period 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 2 ITT analysis set included non-responders (QIDS-SR16 total score >=11) to placebo treatment in Period 1 and were then randomly re-assigned to a treatment group in Period 2. Only placebo participants with a QIDS-SR16 score >= 11 at End Point Period 1 who were re-randomized in Period 2 are included in the Period 2 summary. |
| Arm/Group Title | Panel A: Period 2 Placebo | Panel A: Period 2 Esketamine 28 mg | Panel A: Period 2 Esketamine 56 mg | Panel A: Period 2 Esketamine 84 mg | Panel B: Period 2 Placebo | Panel B: Period 2 Esketamine 14 mg | Panel B: Period 2 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who were non-responders at the end of Period 1 in Panel A (with Quick Inventory of Depressive Symptomatology - 16-item Self Report (QIDS-SR16) score >=11) were randomly re-assigned to receive same Placebo (1 spray to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly re-assigned to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders with QIDS-SR 16 score >=11 received placebo intranasally (1 spray of placebo into each nostril at 0 and 5 minutes) on Days 8 and 11 of Period 2. | Participants who received placebo in Period 1 and were non-responders with QIDS-SR16 score >=11 received esketamine 14 mg intranasally (1 spray of esketamine into one nostril and 1 spray of placebo in other nostril at 0 minutes and 1 spray of placebo in each nostril at 5 minutes) in Period 2. | Participants who were responders (with QIDS-SR16 score <11) at the end of Period 1 in Panel B continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2. |
| Measure Participants | 6 | 8 | 9 | 5 | 5 | 5 | 3 |
| Least Squares Mean (Standard Error) [Unit on a scale] |
-2.0
(1.50)
|
-3.1
(1.35)
|
-2.0
(1.41)
|
-3.3
(1.48)
|
-2.1
(1.78)
|
-5.7
(1.78)
|
-1.5
(2.31)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 1) and Endpoint (Day 8) of Period 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 1 ITT analysis set included all participants randomly assigned to treatment in period 1. |
| Arm/Group Title | Panel A: Period 1 Placebo | Panel A: Period 1 Esketamine 28 mg | Panel A: Period 1 Esketamine 56 mg | Panel A: Period 1 Esketamine 84 mg | Panel B: Period 1 Placebo | Panel B: Period 1 Esketamine 14 mg | Panel B: Period 1 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants self administered placebo intranasally (1 spray to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 28 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 84 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered placebo intranasally (1 spray to each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. |
| Measure Participants | 33 | 11 | 11 | 12 | 21 | 11 | 9 |
| Median (Full Range) [Units on a scale] |
5.0
|
4.0
|
4.0
|
4.0
|
4.0
|
4.0
|
3.0
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 8) and Endpoint (Day 15) of Period 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 2 ITT analysis set included non-responders (QIDS-SR16 total score >=11) to placebo treatment in Period 1 and were then randomly re-assigned to a treatment group in Period 2. Only placebo participants with a QIDS-SR16 score >= 11 at End Point Period 1 who were re-randomized in Period 2 are included in the Period 2 summary. |
| Arm/Group Title | Panel A: Period 2 Placebo | Panel A: Period 2 Esketamine 28 mg | Panel A: Period 2 Esketamine 56 mg | Panel A: Period 2 Esketamine 84 mg | Panel B: Period 2 Placebo | Panel B: Period 2 Esketamine 14 mg | Panel B: Period 2 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who were non-responders at the end of Period 1 in Panel A (with Quick Inventory of Depressive Symptomatology - 16-item Self Report (QIDS-SR16) score >=11) were randomly re-assigned to receive same Placebo (1 spray to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly re-assigned to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders with QIDS-SR 16 score >=11 received placebo intranasally (1 spray of placebo into each nostril at 0 and 5 minutes) on Days 8 and 11 of Period 2. | Participants who received placebo in Period 1 and were non-responders with QIDS-SR16 score >=11 received esketamine 14 mg intranasally (1 spray of esketamine into one nostril and 1 spray of placebo in other nostril at 0 minutes and 1 spray of placebo in each nostril at 5 minutes) in Period 2. | Participants who were responders (with QIDS-SR16 score <11) at the end of Period 1 in Panel B continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2. |
| Measure Participants | 6 | 8 | 9 | 5 | 5 | 5 | 3 |
| Median (Full Range) [Units on a scale] |
5.0
|
4.0
|
5.0
|
4.0
|
4.0
|
3.0
|
4.0
|
| Title | 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 |
|---|---|
| Description | 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). |
| Time Frame | Baseline (Day 1) and Endpoint (Day 8) of Period 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 1 ITT analysis set included all participants randomly assigned to treatment in period 1. |
| Arm/Group Title | Panel A: Period 1 Placebo | Panel A: Period 1 Esketamine 28 mg | Panel A: Period 1 Esketamine 56 mg | Panel A: Period 1 Esketamine 84 mg | Panel B: Period 1 Placebo | Panel B: Period 1 Esketamine 14 mg | Panel B: Period 1 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants self administered placebo intranasally (1 spray to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 28 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 84 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered placebo intranasally (1 spray to each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. |
| Measure Participants | 33 | 11 | 11 | 12 | 21 | 11 | 9 |
| Least Squares Mean (Standard Error) [Unit on a scale] |
-1.7
(0.88)
|
-1.5
(1.34)
|
-3.1
(1.34)
|
-5.1
(1.30)
|
-1.7
(0.68)
|
-1.9
(0.94)
|
-3.2
(1.03)
|
| Title | 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 |
|---|---|
| Description | 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). |
| Time Frame | Baseline (Day 8) and Endpoint (Day 15) of Period 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 2 ITT analysis set included non-responders (QIDS-SR16 total score >=11) to placebo treatment in Period 1 and were then randomly re-assigned to a treatment group in Period 2. Only placebo participants with a QIDS-SR16 score >= 11 at End Point Period 1 who were re-randomized in Period 2 are included in the Period 2 summary. |
| Arm/Group Title | Panel A: Period 2 Placebo | Panel A: Period 2 Esketamine 28 mg | Panel A: Period 2 Esketamine 56 mg | Panel A: Period 2 Esketamine 84 mg | Panel B: Period 2 Placebo | Panel B: Period 2 Esketamine 14 mg | Panel B: Period 2 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who were non-responders at the end of Period 1 in Panel A (with Quick Inventory of Depressive Symptomatology - 16-item Self Report (QIDS-SR16) score >=11) were randomly re-assigned to receive same Placebo (1 spray to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly re-assigned to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders with QIDS-SR 16 score >=11 received placebo intranasally (1 spray of placebo into each nostril at 0 and 5 minutes) on Days 8 and 11 of Period 2. | Participants who received placebo in Period 1 and were non-responders with QIDS-SR16 score >=11 received esketamine 14 mg intranasally (1 spray of esketamine into one nostril and 1 spray of placebo in other nostril at 0 minutes and 1 spray of placebo in each nostril at 5 minutes) in Period 2. | Participants who were responders (with QIDS-SR16 score <11) at the end of Period 1 in Panel B continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2. |
| Measure Participants | 6 | 8 | 9 | 5 | 5 | 5 | 3 |
| Least Squares Mean (Standard Error) [Unit on a scale] |
0.4
(1.02)
|
-1.6
(0.87)
|
1.0
(0.98)
|
-0.9
(1.02)
|
-2.7
(1.68)
|
-6.6
(1.68)
|
-0.7
(2.27)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 1) and Endpoint (Day 8) of Period 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 1 ITT analysis set included all participants randomly assigned to treatment in period 1. |
| Arm/Group Title | Panel A: Period 1 Placebo | Panel A: Period 1 Esketamine 28 mg | Panel A: Period 1 Esketamine 56 mg | Panel A: Period 1 Esketamine 84 mg | Panel B: Period 1 Placebo | Panel B: Period 1 Esketamine 14 mg | Panel B: Period 1 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants self administered placebo intranasally (1 spray to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 28 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 84 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1. | Participants self administered placebo intranasally (1 spray to each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. |
| Measure Participants | 33 | 11 | 11 | 12 | 21 | 11 | 9 |
| Median (Full Range) [Unit on a scale] |
3.0
|
3.0
|
3.0
|
3.0
|
3.0
|
3.0
|
3.0
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 8) and Endpoint (Day 15) of Period 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Period 2 ITT analysis set included non-responders (QIDS-SR16 total score >=11) to placebo treatment in Period 1 and were then randomly re-assigned to a treatment group in Period 2. Only placebo participants with a QIDS-SR16 score >= 11 at End Point Period 1 who were re-randomized in Period 2 are included in the Period 2 summary. |
| Arm/Group Title | Panel A: Period 2 Placebo | Panel A: Period 2 Esketamine 28 mg | Panel A: Period 2 Esketamine 56 mg | Panel A: Period 2 Esketamine 84 mg | Panel B: Period 2 Placebo | Panel B: Period 2 Esketamine 14 mg | Panel B: Period 2 Esketamine 56 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants who were non-responders at the end of Period 1 in Panel A (with Quick Inventory of Depressive Symptomatology - 16-item Self Report (QIDS-SR16) score >=11) were randomly re-assigned to receive same Placebo (1 spray to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly re-assigned to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR 16 score >=11) were randomly re-assigned to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2. | Participants who were non-responders with QIDS-SR 16 score >=11 received placebo intranasally (1 spray of placebo into each nostril at 0 and 5 minutes) on Days 8 and 11 of Period 2. | Participants who received placebo in Period 1 and were non-responders with QIDS-SR16 score >=11 received esketamine 14 mg intranasally (1 spray of esketamine into one nostril and 1 spray of placebo in other nostril at 0 minutes and 1 spray of placebo in each nostril at 5 minutes) in Period 2. | Participants who were responders (with QIDS-SR16 score <11) at the end of Period 1 in Panel B continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2. |
| Measure Participants | 6 | 8 | 9 | 5 | 5 | 5 | 3 |
| Median (Full Range) [Unit on a scale] |
3.0
|
3.0
|
4.0
|
3.0
|
3.0
|
3.0
|
3.0
|
Adverse Events
| Time Frame | Up to 21 weeks | |||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety analysis set for double-blind and open-label phase included all randomized participants who receive at least 1 dose of study drug in the respective phases. For follow-up phase safety population included all participants who entered in follow up phase. | |||||||||||||||||||||||||||||||||||||||||||||
| Arm/Group Title | Placebo (Panel A and B: Period 1) | Esketamine 28 mg (Panel A: Period 1) | Placebo (Panel A and B: Period 2) QIDS >=11 Participants | Placebo to Esketamine 14mg (Panel B: Period 2) | Placebo to Esketamine 28mg (Panel A: Period 2) | Placebo to Esketamine 56mg (Panel A and B: Period 2) | Placebo to Esketamine 84 mg (Panel A: Period 2) | Placebo (Panel A and Panel B: Period 2) | Esketamine 14 mg (Panel B: Period 2) | Esketamine 28 mg (Panel A: Period 2) | Esketamine 56 mg (Panel A and B: Period 2) | Placebo/Placebo/Open Label Esketamine (Panel A and B) | Placebo/Esketamine/Open Label Esketamine (Panel A and B) | Esketamine/Esketamine/Open Label Esketamine (Panel A and B) | Placebo: Follow up Phase | Esketamine 14 mg: Follow up Phase | Esketamine 28 mg: Follow up Phase | Esketamine 56 mg: Follow up Phase | Esketamine 84 mg: Follow up Phase | Esketamine 14 mg (Panel B: Period 1) | Esketamine 56 mg (Panel A and B: Period 1) | Esketamine 84 mg (Panel A: Period 1) | Esketamine 84 mg (Panel A: Period 2) | |||||||||||||||||||||||
| Arm/Group Description | Panel A: Participants self-administered placebo intranasally (1 spray to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1 in Panel A. Panel B: Participants self-administered placebo intranasally (1 spray to each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1 in Panel B. | Participants self administered esketamine 28 milligram (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 1 and 4 of Period 1 in Panel A. | Panel A: Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly reassigned to receive same Placebo (1 spray to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2 in Panel A. Panel B: Participants who were non-responders with QIDS-SR16 score >=11 at the end of Period 1 were randomly assigned to receive placebo intranasally (1 spray of placebo into each nostril at 0 and 5 minutes using 4 separate devices) on Days 8 and 11 of Period 2 in Panel B. | Participants who received placebo in Period 1 and were non-responders with QIDS-SR16 score >=11 at the end of Period 1 were randomly reassigned to receive esketamine 14 mg intranasally (1 spray of esketamine 14 mg into once nostril and 1 spray of placebo in other nostril at 0 minute and 1 spray of placebo in each nostril at 5 minutes using 4 separate devices) on Days 8 and 11 in Period 2 of Panel B. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly reassigned to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2 in Panel A. | Panel A: Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly reassigned to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2 in Panel A. Panel B: Participants who were responders (with QIDS-SR16 score <11) at the end of Period 1 in Panel B continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2 of Panel B. | Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly reassigned to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2 in Panel A. | All participants who received placebo in Period 2 of Panel A and B (including participants with QIDS-SR16 score >=11 and QIDS-SR16 score <11) in double-blind phase. | Participants who received esketamine 14 mg in Period 1 of Panel B continued to receive esketamine 14 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2 of Panel B. | Participants who received esketamine 28 mg in Period 1 of Panel A continued to receive esketamine 28 mg (1 spray of esketamine 14 mg to each nostril at 0 minute and 1 spray of placebo to each nostril at 5 and 10 minutes) on Days 8 and 11 of Period 2 in Panel A. | Panel A: Participants who were non-responders at the end of Period 1 in Panel A (with QIDS-SR16 score >=11) were randomly re-assigned to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 of Period 2. Panel B: Participants who were responders (with QIDS-SR16 score <11) at the end of Period 1 in Panel B continued to receive esketamine 56 mg (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 8 and 11 in Period 2. | Panel A: Participants who received Placebo in Period 1 and 2 of Panel A and elected to continue with open label (OL) phase received up to 9 single doses of intranasal esketamine on Days 15,18,22,25,32, 39, 46,60,74. Doses for optional OL phase included 28, 56, and 84 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18,22,25,32,39,46 could be adjusted to next lower or higher dose, based on investigator's clinical judgment. Same dose administered on Day 46 was administered on Day 60, 74. Panel B: Participants who received Placebo in Period 1 and 2 of Panel A and elected to continue with OL phase received up to 4 single doses of intranasal esketamine on Days 15, 18, 22, 25. Doses for OL phase included 14, 28, 56 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18, 22, 25 could be adjusted to next lower or higher dose, based on investigator's clinical judgment. | Panel A: Participants who received Placebo in Period 1, esketamine in Period 2 and elected to continue with OL phase received up to 9 single doses of intranasal esketamine on Days 15,18,22,25,32,39,46,60, 74. Doses for OL phase included 28,56,84 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18,22,25,32,39, 46 could be adjusted to the next lower or higher dose, based on the investigator's clinical judgment. Same dose administered on Day 46 was administered on Day 60,74. Panel B: Participants who received Placebo in Period 1 and esketamine in Period 2 of Panel A and elected to continue with OL phase received up to 4 single doses of intranasal esketamine on Days 15,18,22,25. Doses for OL phase included 14,28,56 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18,22,25 could be adjusted to next lower or higher dose, based on the investigator's clinical judgment. | Panel A: Participants who received esketamine in Period 1 and 2 and elected to continue with open label phase received up to 9 single doses of intranasal esketamine on Days 15,18,22,25,32,39,46,60,74. Doses for OL treatment phase included 28, 56, 84 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18, 22,25,32,39, 46 could be adjusted to the next lower or higher dose, based on the investigator's clinical judgment. Same dose administered on Day 46 was administered on Day 60,74.Panel B: Participants who received esketamine in Period 1 and 2 of Panel A and elected to continue with OL phase received up to 4 single doses of intranasal esketamine on Days 15, 18, 22, 25. Doses for OL phase included 14, 28, 56 mg of esketamine. All participants started with intranasal esketamine 56 mg on Day 15. Subsequent doses on Days 18, 22, 25 could be adjusted to the next lower or higher dose, based on the investigator's clinical judgment. | All participants whose last dose was Placebo in the double-blind phase or open label phase and were not consent withdrawn were followed for safety for 8 weeks. | All participants whose last dose was esketamine 14 mg in the double-blind phase or open label phase and were not consent withdrawn were followed for safety for 8 weeks. | All participants whose last dose was esketamine 28 mg in the double-blind phase or open label phase and were not consent withdrawn were followed for safety for 8 weeks. | All participants whose last dose was esketamine 56 mg in the double-blind phase or open label phase and were not consent withdrawn were followed for safety for 8 weeks. | All participants whose last dose was esketamine 84 mg in the double-blind phase or open label phase and were not consent withdrawn were followed for safety for 8 weeks. | Participants self administered esketamine 14 mg intranasally (1 spray of esketamine 14 mg into one nostril and 1 spray of placebo into other nostril at 0 minute and then 1 spray of placebo to each nostril at 5 minutes) on Days 1 and 4 of Period 1 in Panel B. | Panel A: Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0 and 5 minute and 1 spray of placebo to each nostril at 10 minutes) on Days 1 and 4 of Period 1. Panel B: Participants self administered esketamine 56 mg intranasally (1 spray of esketamine 14 mg into each nostril at 0 and 5 minutes) on Days 1 and 4 of Period 1. | Participants self administered esketamine 84 mg intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 1 and 4 of Period 1 in Panel A. | Participants who received esketamine 84 mg in Period 1 of Panel A continued to receive esketamine 84 mg (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) on Days 8 and 11 of Period 2 in Panel A. | |||||||||||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||||||||||||||||||||
| Placebo (Panel A and B: Period 1) | Esketamine 28 mg (Panel A: Period 1) | Placebo (Panel A and B: Period 2) QIDS >=11 Participants | Placebo to Esketamine 14mg (Panel B: Period 2) | Placebo to Esketamine 28mg (Panel A: Period 2) | Placebo to Esketamine 56mg (Panel A and B: Period 2) | Placebo to Esketamine 84 mg (Panel A: Period 2) | Placebo (Panel A and Panel B: Period 2) | Esketamine 14 mg (Panel B: Period 2) | Esketamine 28 mg (Panel A: Period 2) | Esketamine 56 mg (Panel A and B: Period 2) | Placebo/Placebo/Open Label Esketamine (Panel A and B) | Placebo/Esketamine/Open Label Esketamine (Panel A and B) | Esketamine/Esketamine/Open Label Esketamine (Panel A and B) | Placebo: Follow up Phase | Esketamine 14 mg: Follow up Phase | Esketamine 28 mg: Follow up Phase | Esketamine 56 mg: Follow up Phase | Esketamine 84 mg: Follow up Phase | Esketamine 14 mg (Panel B: Period 1) | Esketamine 56 mg (Panel A and B: Period 1) | Esketamine 84 mg (Panel A: Period 1) | Esketamine 84 mg (Panel A: Period 2) | ||||||||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||||||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||||||||||||||||||||
| Placebo (Panel A and B: Period 1) | Esketamine 28 mg (Panel A: Period 1) | Placebo (Panel A and B: Period 2) QIDS >=11 Participants | Placebo to Esketamine 14mg (Panel B: Period 2) | Placebo to Esketamine 28mg (Panel A: Period 2) | Placebo to Esketamine 56mg (Panel A and B: Period 2) | Placebo to Esketamine 84 mg (Panel A: Period 2) | Placebo (Panel A and Panel B: Period 2) | Esketamine 14 mg (Panel B: Period 2) | Esketamine 28 mg (Panel A: Period 2) | Esketamine 56 mg (Panel A and B: Period 2) | Placebo/Placebo/Open Label Esketamine (Panel A and B) | Placebo/Esketamine/Open Label Esketamine (Panel A and B) | Esketamine/Esketamine/Open Label Esketamine (Panel A and B) | Placebo: Follow up Phase | Esketamine 14 mg: Follow up Phase | Esketamine 28 mg: Follow up Phase | Esketamine 56 mg: Follow up Phase | Esketamine 84 mg: Follow up Phase | Esketamine 14 mg (Panel B: Period 1) | Esketamine 56 mg (Panel A and B: Period 1) | Esketamine 84 mg (Panel A: Period 1) | Esketamine 84 mg (Panel A: Period 2) | ||||||||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 1/23 (4.3%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 1/39 (2.6%) | 1/42 (2.4%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Oesophagitis | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 1/23 (4.3%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| General disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| General Physical Health Deterioration | 0/1 (0%) | 0/3 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/11 (0%) | 0/8 (0%) | 0/16 (0%) | 0/12 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 1/42 (2.4%) | 1/11 (9.1%) | 1/20 (5%) | 1/12 (8.3%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||||||||||||||||||||||||||||||||||
| Ectopic Pregnancy | 0/1 (0%) | 0/3 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/11 (0%) | 0/8 (0%) | 0/16 (0%) | 0/12 (0%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Completed Suicide | 0/1 (0%) | 0/3 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/11 (0%) | 0/8 (0%) | 0/16 (0%) | 0/12 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 1/39 (2.6%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Confusional State | 0/1 (0%) | 0/3 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/11 (0%) | 0/8 (0%) | 0/16 (0%) | 0/12 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
Other (Not Including Serious) Adverse Events |
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| Placebo (Panel A and B: Period 1) | Esketamine 28 mg (Panel A: Period 1) | Placebo (Panel A and B: Period 2) QIDS >=11 Participants | Placebo to Esketamine 14mg (Panel B: Period 2) | Placebo to Esketamine 28mg (Panel A: Period 2) | Placebo to Esketamine 56mg (Panel A and B: Period 2) | Placebo to Esketamine 84 mg (Panel A: Period 2) | Placebo (Panel A and Panel B: Period 2) | Esketamine 14 mg (Panel B: Period 2) | Esketamine 28 mg (Panel A: Period 2) | Esketamine 56 mg (Panel A and B: Period 2) | Placebo/Placebo/Open Label Esketamine (Panel A and B) | Placebo/Esketamine/Open Label Esketamine (Panel A and B) | Esketamine/Esketamine/Open Label Esketamine (Panel A and B) | Placebo: Follow up Phase | Esketamine 14 mg: Follow up Phase | Esketamine 28 mg: Follow up Phase | Esketamine 56 mg: Follow up Phase | Esketamine 84 mg: Follow up Phase | Esketamine 14 mg (Panel B: Period 1) | Esketamine 56 mg (Panel A and B: Period 1) | Esketamine 84 mg (Panel A: Period 1) | Esketamine 84 mg (Panel A: Period 2) | ||||||||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/54 (50%) | 8/11 (72.7%) | 15/23 (65.2%) | 5/5 (100%) | 4/8 (50%) | 11/12 (91.7%) | 5/5 (100%) | 12/23 (52.2%) | 11/16 (68.8%) | 8/16 (50%) | 26/32 (81.3%) | 23/23 (100%) | 22/27 (81.5%) | 39/46 (84.8%) | 0/1 (0%) | 1/4 (25%) | 4/12 (33.3%) | 10/39 (25.6%) | 7/42 (16.7%) | 6/11 (54.5%) | 18/20 (90%) | 10/12 (83.3%) | 12/17 (70.6%) | |||||||||||||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Bradycardia | 0/54 (0%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Palpitations | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 1/23 (4.3%) | 1/16 (6.3%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Sinus Bradycardia | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Sinus Tachycardia | 0/1 (0%) | 0/3 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/11 (0%) | 0/8 (0%) | 0/16 (0%) | 0/12 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Ear Congestion | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Vertigo | 0/54 (0%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 2/12 (16.7%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 1/16 (6.3%) | 2/32 (6.3%) | 2/23 (8.7%) | 3/27 (11.1%) | 2/46 (4.3%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Eye disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Accommodation Disorder | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 1/27 (3.7%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Conjunctival Hyperaemia | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Vision Blurred | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 1/5 (20%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 1/23 (4.3%) | 1/27 (3.7%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 2/17 (11.8%) | |||||||||||||||||||||||
| Visual Impairment | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 1/23 (4.3%) | 1/27 (3.7%) | 3/46 (6.5%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Conjunctivitis Allergic | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Abdominal Pain | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 1/23 (4.3%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Abdominal Pain Upper | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Hypoaesthesia Oral | 0/54 (0%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 2/12 (16.7%) | 1/5 (20%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 3/32 (9.4%) | 2/23 (8.7%) | 1/27 (3.7%) | 2/46 (4.3%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 3/20 (15%) | 1/12 (8.3%) | 2/17 (11.8%) | |||||||||||||||||||||||
| Nausea | 5/54 (9.3%) | 2/11 (18.2%) | 3/23 (13%) | 1/5 (20%) | 0/8 (0%) | 2/12 (16.7%) | 2/5 (40%) | 2/23 (8.7%) | 1/16 (6.3%) | 1/16 (6.3%) | 3/32 (9.4%) | 4/23 (17.4%) | 6/27 (22.2%) | 6/46 (13%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 5/20 (25%) | 2/12 (16.7%) | 2/17 (11.8%) | |||||||||||||||||||||||
| Oral Discomfort | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 1/27 (3.7%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Paraesthesia Oral | 0/54 (0%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 2/23 (8.7%) | 0/27 (0%) | 3/46 (6.5%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Salivary Hypersecretion | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Stomatitis | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Vomiting | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 3/27 (11.1%) | 3/46 (6.5%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 1/39 (2.6%) | 0/42 (0%) | 1/11 (9.1%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Dry Mouth | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/12 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Diarrhoea | 1/54 (1.9%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Erosive Oesophagitis | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Gastritis | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/32 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Oesophageal Stenosis | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| General disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Asthenia | 0/54 (0%) | 0/11 (0%) | 2/23 (8.7%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 2/23 (8.7%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 2/23 (8.7%) | 0/27 (0%) | 2/46 (4.3%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 1/39 (2.6%) | 0/42 (0%) | 1/11 (9.1%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Chills | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Discomfort | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Energy Increased | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Feeling Abnormal | 1/54 (1.9%) | 2/11 (18.2%) | 1/23 (4.3%) | 2/5 (40%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 1/23 (4.3%) | 4/16 (25%) | 0/16 (0%) | 3/32 (9.4%) | 4/23 (17.4%) | 4/27 (14.8%) | 7/46 (15.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 2/11 (18.2%) | 4/20 (20%) | 1/12 (8.3%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Feeling Drunk | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 1/32 (3.1%) | 1/23 (4.3%) | 0/27 (0%) | 3/46 (6.5%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Feeling Hot | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Feeling Jittery | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Gait Disturbance | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 1/27 (3.7%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Hangover | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 1/16 (6.3%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Injection Site Haemorrhage | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Malaise | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 2/23 (8.7%) | 1/27 (3.7%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 1/39 (2.6%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Pain | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Product Taste Abnormal | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Pyrexia | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Sluggishness | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Thirst | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||||||||||||||||||||
| Cystitis | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 1/27 (3.7%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Nasopharyngitis | 1/54 (1.9%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 1/27 (3.7%) | 2/46 (4.3%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 5/39 (12.8%) | 1/42 (2.4%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Gastroenteritis | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Pharyngitis | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||||||||||||||||||
| Contusion | 1/54 (1.9%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Scratch | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Skin Abrasion | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 1/16 (6.3%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Arthropod Bite | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Investigations | ||||||||||||||||||||||||||||||||||||||||||||||
| Blood Pressure Diastolic Increased | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 1/16 (6.3%) | 0/32 (0%) | 0/23 (0%) | 1/27 (3.7%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Blood Pressure Increased | 1/54 (1.9%) | 0/11 (0%) | 1/23 (4.3%) | 1/5 (20%) | 0/8 (0%) | 0/12 (0%) | 1/5 (20%) | 1/23 (4.3%) | 1/16 (6.3%) | 0/16 (0%) | 1/32 (3.1%) | 4/23 (17.4%) | 3/27 (11.1%) | 3/46 (6.5%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 2/20 (10%) | 0/12 (0%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Blood Pressure Systolic Increased | 0/54 (0%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Oxygen Saturation Decreased | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 1/5 (20%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| C-Reactive Protein Increased | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Decreased Appetite | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 1/39 (2.6%) | 1/42 (2.4%) | 1/11 (9.1%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Back Pain | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 1/27 (3.7%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Limb Discomfort | 1/54 (1.9%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Muscle Tightness | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Myalgia | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Pain in Extremity | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Muscle Spasms | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Akathisia | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 1/5 (20%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Altered State of Consciousness | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Coordination Abnormal | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 1/27 (3.7%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Disturbance in Attention | 1/54 (1.9%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Dizziness | 1/54 (1.9%) | 4/11 (36.4%) | 0/23 (0%) | 2/5 (40%) | 0/8 (0%) | 4/12 (33.3%) | 3/5 (60%) | 0/23 (0%) | 2/16 (12.5%) | 2/16 (12.5%) | 11/32 (34.4%) | 7/23 (30.4%) | 9/27 (33.3%) | 14/46 (30.4%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 7/20 (35%) | 5/12 (41.7%) | 5/17 (29.4%) | |||||||||||||||||||||||
| Dizziness Postural | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 2/32 (6.3%) | 2/23 (8.7%) | 0/27 (0%) | 4/46 (8.7%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 1/39 (2.6%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Dysaesthesia | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 1/23 (4.3%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Dysgeusia | 9/54 (16.7%) | 2/11 (18.2%) | 6/23 (26.1%) | 1/5 (20%) | 1/8 (12.5%) | 2/12 (16.7%) | 3/5 (60%) | 4/23 (17.4%) | 2/16 (12.5%) | 1/16 (6.3%) | 4/32 (12.5%) | 4/23 (17.4%) | 6/27 (22.2%) | 9/46 (19.6%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 4/20 (20%) | 3/12 (25%) | 4/17 (23.5%) | |||||||||||||||||||||||
| Dysgraphia | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 1/27 (3.7%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Dyskinesia | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Headache | 4/54 (7.4%) | 4/11 (36.4%) | 5/23 (21.7%) | 0/5 (0%) | 2/8 (25%) | 3/12 (25%) | 1/5 (20%) | 4/23 (17.4%) | 1/16 (6.3%) | 2/16 (12.5%) | 3/32 (9.4%) | 4/23 (17.4%) | 5/27 (18.5%) | 5/46 (10.9%) | 0/1 (0%) | 1/4 (25%) | 0/12 (0%) | 0/39 (0%) | 4/42 (9.5%) | 2/11 (18.2%) | 4/20 (20%) | 2/12 (16.7%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Hypersomnia | 0/54 (0%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 1/16 (6.3%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Hypoaesthesia | 0/54 (0%) | 1/11 (9.1%) | 1/23 (4.3%) | 1/5 (20%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 1/23 (4.3%) | 3/16 (18.8%) | 0/16 (0%) | 4/32 (12.5%) | 3/23 (13%) | 4/27 (14.8%) | 8/46 (17.4%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 3/20 (15%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Loss of Consciousness | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Mental Impairment | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 1/27 (3.7%) | 2/46 (4.3%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Paraesthesia | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 1/23 (4.3%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 1/42 (2.4%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Psychomotor Hyperactivity | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 1/16 (6.3%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Sedation | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/12 (0%) | 1/5 (20%) | 0/23 (0%) | 0/16 (0%) | 1/16 (6.3%) | 1/32 (3.1%) | 3/23 (13%) | 2/27 (7.4%) | 3/46 (6.5%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 3/20 (15%) | 0/12 (0%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Slow Speech | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 2/46 (4.3%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Somnolence | 3/54 (5.6%) | 1/11 (9.1%) | 7/23 (30.4%) | 1/5 (20%) | 0/8 (0%) | 2/12 (16.7%) | 0/5 (0%) | 6/23 (26.1%) | 1/16 (6.3%) | 1/16 (6.3%) | 5/32 (15.6%) | 7/23 (30.4%) | 5/27 (18.5%) | 5/46 (10.9%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 2/11 (18.2%) | 2/20 (10%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Syncope | 0/54 (0%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Tremor | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 1/27 (3.7%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 1/39 (2.6%) | 0/42 (0%) | 1/11 (9.1%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Tunnel Vision | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 1/27 (3.7%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 2/12 (16.7%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Visual Field Defect | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Dysarthria | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 1/27 (3.7%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Sensory Disturbance | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Anxiety | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 1/27 (3.7%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Confusional State | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Daydreaming | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Dissociation | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 1/5 (20%) | 0/8 (0%) | 4/12 (33.3%) | 1/5 (20%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 8/32 (25%) | 2/23 (8.7%) | 4/27 (14.8%) | 8/46 (17.4%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 6/20 (30%) | 3/12 (25%) | 2/17 (11.8%) | |||||||||||||||||||||||
| Dissociative Disorder | 0/54 (0%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/12 (0%) | 1/5 (20%) | 0/23 (0%) | 0/16 (0%) | 1/16 (6.3%) | 1/32 (3.1%) | 4/23 (17.4%) | 2/27 (7.4%) | 3/46 (6.5%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 3/12 (25%) | 3/17 (17.6%) | |||||||||||||||||||||||
| Dysphoria | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Fear | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Hallucination, Visual | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 1/16 (6.3%) | 1/32 (3.1%) | 0/23 (0%) | 2/27 (7.4%) | 2/46 (4.3%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Illusion | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 1/23 (4.3%) | 0/27 (0%) | 2/46 (4.3%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Insomnia | 1/54 (1.9%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 2/12 (16.7%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 2/32 (6.3%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 1/4 (25%) | 1/12 (8.3%) | 1/39 (2.6%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Irritability | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 1/23 (4.3%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 2/27 (7.4%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Merycism | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Somatic Hallucination | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Suspiciousness | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Thinking Abnormal | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 1/23 (4.3%) | 1/27 (3.7%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Depersonalisation | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 2/23 (8.7%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Persecutory Delusion | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Suicidal Ideation | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Bladder Pain | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 1/12 (8.3%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Micturition Urgency | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Polyuria | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Dry Throat | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Dyspnoea | 0/54 (0%) | 0/11 (0%) | 1/23 (4.3%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 1/23 (4.3%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 3/46 (6.5%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Hyperventilation | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 1/27 (3.7%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Nasal Congestion | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 1/5 (20%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Nasal Discomfort | 3/54 (5.6%) | 0/11 (0%) | 2/23 (8.7%) | 0/5 (0%) | 0/8 (0%) | 2/12 (16.7%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 3/23 (13%) | 2/27 (7.4%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Nasal Dryness | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Nasal Mucosal Disorder | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Nasal Obstruction | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Nasal Oedema | 1/54 (1.9%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 1/5 (20%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Nasal Pruritus | 2/54 (3.7%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 1/5 (20%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 1/11 (9.1%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Oropharyngeal Pain | 2/54 (3.7%) | 0/11 (0%) | 2/23 (8.7%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 1/5 (20%) | 1/23 (4.3%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 2/23 (8.7%) | 2/27 (7.4%) | 3/46 (6.5%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 1/12 (8.3%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Pharyngeal Disorder | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 1/5 (20%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Pharyngeal Hypoaesthesia | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 1/5 (20%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 1/46 (2.2%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Rhinorrhoea | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 1/23 (4.3%) | 1/27 (3.7%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 1/39 (2.6%) | 0/42 (0%) | 1/11 (9.1%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Sneezing | 1/54 (1.9%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 1/23 (4.3%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Throat Irritation | 0/54 (0%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 1/5 (20%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 2/23 (8.7%) | 2/27 (7.4%) | 3/46 (6.5%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 2/17 (11.8%) | |||||||||||||||||||||||
| Upper-Airway Cough Syndrome | 2/54 (3.7%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 1/5 (20%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Dermatitis Contact | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 1/12 (8.3%) | 0/17 (0%) | |||||||||||||||||||||||
| Hyperhidrosis | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 2/12 (16.7%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 2/32 (6.3%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Pruritus | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Scab | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 1/16 (6.3%) | 0/32 (0%) | 0/23 (0%) | 1/27 (3.7%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Vascular disorders | ||||||||||||||||||||||||||||||||||||||||||||||
| Hot Flush | 0/54 (0%) | 1/11 (9.1%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 0/32 (0%) | 1/23 (4.3%) | 0/27 (0%) | 0/46 (0%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 0/20 (0%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
| Hypertension | 2/54 (3.7%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 3/12 (25%) | 0/5 (0%) | 0/23 (0%) | 1/16 (6.3%) | 0/16 (0%) | 3/32 (9.4%) | 0/23 (0%) | 1/27 (3.7%) | 2/46 (4.3%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 1/20 (5%) | 1/12 (8.3%) | 1/17 (5.9%) | |||||||||||||||||||||||
| Peripheral Coldness | 0/54 (0%) | 0/11 (0%) | 0/23 (0%) | 0/5 (0%) | 0/8 (0%) | 0/12 (0%) | 0/5 (0%) | 0/23 (0%) | 0/16 (0%) | 0/16 (0%) | 1/32 (3.1%) | 0/23 (0%) | 0/27 (0%) | 2/46 (4.3%) | 0/1 (0%) | 0/4 (0%) | 0/12 (0%) | 0/39 (0%) | 0/42 (0%) | 0/11 (0%) | 2/20 (10%) | 0/12 (0%) | 0/17 (0%) | |||||||||||||||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
| Name/Title | Senior Director |
|---|---|
| Organization | Janssen Research & Development, LLC |
| Phone | 844-434-4210 |
| ClinicalTrialDisclosure@its.jnj.com |
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01998958
Other Study ID Numbers:
- CR102968
- 2013-004005-11
- JNJ-54135419
- ESKETINTRD2003
First Posted:
Dec 3, 2013
Last Update Posted:
Jun 2, 2020
Last Verified:
May 1, 2020