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    Clinical Trial Results:
    A multi-center, randomized, subject and investigatorblinded, placebo-controlled, active comparator, parallelgroup proof of concept study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of MIJ821 in patients with treatment-resistant depression

    Summary
    EudraCT number
    		 2018-003002-12
    Trial protocol
    		 ES  
    Global end of trial date
    23 Mar 2020

    Results information
    Results version number
    		 v3(current)
    This version publication date
    28 Aug 2021
    First version publication date
    17 Mar 2021
    Other versions
    		 v1 , v2
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CMIJ821X2201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03756129
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    23 Mar 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Mar 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to assess efficacy of MIJ821 in treatment-resistant depression.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Feb 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 16
    Country: Number of subjects enrolled
    United States: 54
    Worldwide total number of subjects
    70
    EEA total number of subjects
    16
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    69
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Overall, 72 subjects were randomized in this study, and 2 of them discontinued from study before receiving any study treatment. All the 70 treated subjects were included in both efficacy and safety analyses. Fifty subjects treated with MIJ821 or ketamine were included in the pharmacokinetic analysis.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MIJ821 0.16 mg/kg weekly
    Arm description
    		 MIJ821 0.16 mg/kg weekly
    Arm type
    		 Experimental

    Investigational medicinal product name
    MIJ821
    Investigational medicinal product code
    MIJ821
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MIJ821 fixed dose of 0.16 mg/kg, one infusion per week from Day 1 to Day 36

    Arm title
    		 MIJ821 0.16 mg/kg biweekly
    Arm description
    		 MIJ821 0.16 mg/kg biweekly
    Arm type
    		 Experimental

    Investigational medicinal product name
    MIJ821
    Investigational medicinal product code
    MIJ821
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MIJ821 fixed dose of 0.16 mg/kg one infusion biweekly on Day 1, Day 15, and Day 29, placebo on Day 8, Day 22 and Day 36

    Arm title
    		 MIJ821 0.32 mg/kg weekly
    Arm description
    		 MIJ821 0.32 mg/kg weekly
    Arm type
    		 Experimental

    Investigational medicinal product name
    MIJ821
    Investigational medicinal product code
    MIJ821
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MIJ821 fixed dose of 0.32 mg/kg, one infusion per week from Day 1 to Day 36

    Arm title
    		 MIJ821 0.32 mg/kg biweekly
    Arm description
    		 MIJ821 0.32 mg/kg biweekly
    Arm type
    		 Experimental

    Investigational medicinal product name
    MIJ821
    Investigational medicinal product code
    MIJ821
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MIJ821 fixed dose of 0.32 mg/kg one infusion biweekly on Day 1, Day 15, and Day 29, placebo on Day 8, Day 22 and Day 36

    Arm title
    		 Ketamine 0.5 mg/kg weekly
    Arm description
    		 Ketamine 0.5 mg/kg weekly
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Ketamine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ketamine fixed dose of 0.5 mg/kg, limiting dose at 40 mg/infusion for subjects over 80 kg, one infusion per week from Day 1 to Day 36 (absence of the ketamine arm in the US)

    Arm title
    		 Placebo weekly
    Arm description
    		 Placebo weekly
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo, one infusion per week from Day 1 to Day 36

    Number of subjects in period 1
    		MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Started
    11
    10
    10
    9
    10
    20
    Completed
    8
    8
    7
    6
    9
    15
    Not completed
    3
    2
    3
    3
    1
    5
         Consent withdrawn by subject
    2
    1
    3
    1
    1
    3
         Physician decision
    -
    -
    -
    -
    -
    1
         Adverse event, non-fatal
    1
    1
    -
    2
    -
    -
         Lost to follow-up
    -
    -
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MIJ821 0.16 mg/kg weekly
    Reporting group description
    		 MIJ821 0.16 mg/kg weekly

    Reporting group title
    MIJ821 0.16 mg/kg biweekly
    Reporting group description
    		 MIJ821 0.16 mg/kg biweekly

    Reporting group title
    MIJ821 0.32 mg/kg weekly
    Reporting group description
    		 MIJ821 0.32 mg/kg weekly

    Reporting group title
    MIJ821 0.32 mg/kg biweekly
    Reporting group description
    		 MIJ821 0.32 mg/kg biweekly

    Reporting group title
    Ketamine 0.5 mg/kg weekly
    Reporting group description
    		 Ketamine 0.5 mg/kg weekly

    Reporting group title
    Placebo weekly
    Reporting group description
    		 Placebo weekly

    Reporting group values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly Total
    Number of subjects
    		 11 10 10 9 10 20 70
    Age Categorical
    Units: Participants
        <=18 years
    		 0 0 0 0 0 0 0
        Between 18 and 65 years
    		 11 9 10 9 10 20 69
        >=65 years
    		 0 1 0 0 0 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 48.6 ( 11.70 ) 53.7 ( 9.33 ) 42.9 ( 14.47 ) 46.6 ( 11.83 ) 52.3 ( 6.96 ) 44.8 ( 10.69 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 2 5 6 6 7 9 35
        Male
    		 9 5 4 3 3 11 35
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0
        Asian
    		 0 0 0 0 0 1 1
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0
        Black or African American
    		 3 4 4 8 0 10 29
        White
    		 8 6 6 1 9 9 39
        More than one race
    		 0 0 0 0 1 0 1
        Unknown or Not Reported
    		 0 0 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    MIJ821 0.16 mg/kg weekly
    Reporting group description
    		 MIJ821 0.16 mg/kg weekly

    Reporting group title
    MIJ821 0.16 mg/kg biweekly
    Reporting group description
    		 MIJ821 0.16 mg/kg biweekly

    Reporting group title
    MIJ821 0.32 mg/kg weekly
    Reporting group description
    		 MIJ821 0.32 mg/kg weekly

    Reporting group title
    MIJ821 0.32 mg/kg biweekly
    Reporting group description
    		 MIJ821 0.32 mg/kg biweekly

    Reporting group title
    Ketamine 0.5 mg/kg weekly
    Reporting group description
    		 Ketamine 0.5 mg/kg weekly

    Reporting group title
    Placebo weekly
    Reporting group description
    		 Placebo weekly

    Subject analysis set title
    Pooled MIJ821 0.16 mg/kg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pooled MIJ821 0.16 mg/kg

    Subject analysis set title
    Pooled MIJ821 0.32 mg/kg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pooled MIJ821 0.32 mg/kg

    Subject analysis set title
    Pooled MIJ821 0.16 mg/kg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pooled MIJ821 0.16 mg/kg

    Subject analysis set title
    Pooled MIJ821 0.32 mg/kg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pooled MIJ821 0.32 mg/kg

    Subject analysis set title
    Pooled MIJ821 0.16 mg/kg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pooled MIJ821 0.16 mg/kg

    Subject analysis set title
    Pooled MIJ821 0.32 mg/kg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pooled MIJ821 0.32 mg/kg

    Subject analysis set title
    Koukopoulos
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Koukopoulos Mixed Depression Rating Scale

    Subject analysis set title
    Angst
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Mixed depression checklist, created by Angst

    Subject analysis set title
    Ghaemi
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Melancholia checklist, created by Ghaemi

    Subject analysis set title
    Ketamine 0.5 mg/kg weekly
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ketamine 0.5 mg/kg weekly

    Subject analysis set title
    Placebo weekly
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo weekly

    Primary: Change from baseline in the total score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 hrs

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    End point title
    		 Change from baseline in the total score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 hrs
    End point description
    Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
    End point type
    Primary
    End point timeframe
    Baseline, and at 24 hours
    End point values
    		 Pooled MIJ821 0.16 mg/kg Pooled MIJ821 0.32 mg/kg Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    21
    19
    10
    20
    Units: Scores on a Scale
        least squares mean (standard error)
    -15.51 ( 1.9 )
    -12.98 ( 1.9 )
    -12.94 ( 2.7 )
    -7.27 ( 1.9 )
    Statistical analysis title
    		 Comparison of adjusted arithmetic mean
    Statistical analysis description
    Comparison of adjusted arithmetic mean: Mean Difference: “Pooled MIJ821 0.32 mg/kg” minus “placebo”. The MIJ821 treatment arms vs placebo are primary.
    Comparison groups
    Pooled MIJ821 0.32 mg/kg v Placebo weekly
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0196
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -5.71
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -9.22
         upper limit
    		 -2.2
    Statistical analysis title
    		 Comparison of adjusted arithmetic mean
    Statistical analysis description
    Comparison of adjusted arithmetic mean: Mean Difference: “Pooled MIJ821 0.16 mg/kg” minus “placebo”. The MIJ821 treatment arms vs placebo are primary.
    Comparison groups
    Placebo weekly v Pooled MIJ821 0.16 mg/kg
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0013
    Method
    		 ANCOVA
    Parameter type
    		 Median difference (net)
    Point estimate
    -8.25
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -11.67
         upper limit
    		 -4.83

    Secondary: Change from baseline in the total score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 hrs

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    End point title
    		 Change from baseline in the total score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 hrs
    End point description
    Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
    End point type
    Secondary
    End point timeframe
    Baseline, and at 48 hours
    End point values
    		 Pooled MIJ821 0.16 mg/kg Pooled MIJ821 0.32 mg/kg Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    19
    16
    4
    19
    Units: Scores on a Scale
        least squares mean (standard error)
    -14.94 ( 2.2 )
    -15.25 ( 2.4 )
    -18.89 ( 4.8 )
    -7.88 ( 2.2 )
    Statistical analysis title
    		 Comparison of adjusted arithmetic mean
    Statistical analysis description
    Comparison of adjusted arithmetic mean: Mean Difference: “Pooled MIJ821 0.16 mg/kg” minus “placebo”.
    Comparison groups
    Pooled MIJ821 0.16 mg/kg v Placebo weekly
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.013
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -7.06
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -11.06
         upper limit
    		 -3.06
    Statistical analysis title
    		 Comparison of adjusted arithmetic mean
    Statistical analysis description
    Comparison of adjusted arithmetic mean: Mean Difference: “Pooled MIJ821 0.32 mg/kg” minus “placebo”.
    Comparison groups
    Pooled MIJ821 0.32 mg/kg v Placebo weekly
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0133
    Method
    		 ANCOVA
    Parameter type
    		 Median difference (net)
    Point estimate
    -7.37
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -11.57
         upper limit
    		 -3.18

    Secondary: Change from baseline in the total score of the Montgomery Asberg Depression Rating Scale (MADRS) at week 6

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    End point title
    		 Change from baseline in the total score of the Montgomery Asberg Depression Rating Scale (MADRS) at week 6
    End point description
    Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
    End point type
    Secondary
    End point timeframe
    Baseline, and at Week 6
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    8
    8
    8
    6
    9
    17
    Units: Scores on a Scale
        least squares mean (standard error)
    -12.71 ( 3.4 )
    -14.08 ( 3.4 )
    -13.04 ( 3.5 )
    -10.68 ( 3.9 )
    -12.86 ( 3.3 )
    -7.62 ( 2.3 )
    Statistical analysis title
    		 Comparison of adjusted arithmetic mean
    Statistical analysis description
    Comparison of adjusted arithmetic mean: Mean Difference: “MIJ821 0.16 mg/kg weekly” minus “placebo”.
    Comparison groups
    MIJ821 0.16 mg/kg weekly v Placebo weekly
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1082
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -5.09
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -10.37
         upper limit
    		 0.19
    Statistical analysis title
    		 Comparison of adjusted arithmetic mean
    Statistical analysis description
    Comparison of adjusted arithmetic mean: Mean Difference: “MIJ821 0.32 mg/kg weekly” minus “placebo”.
    Comparison groups
    MIJ821 0.32 mg/kg weekly v Placebo weekly
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0993
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -5.42
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -10.83
         upper limit
    		 -0.02
    Statistical analysis title
    		 Comparison of adjusted arithmetic mean
    Statistical analysis description
    Comparison of adjusted arithmetic mean: Mean Difference: “MIJ821 0.16 mg/kg biweekly” minus “placebo”.
    Comparison groups
    MIJ821 0.16 mg/kg biweekly v Placebo weekly
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0598
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -6.46
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -11.78
         upper limit
    		 -1.15
    Statistical analysis title
    		 Comparison of adjusted arithmetic mean
    Statistical analysis description
    Comparison of adjusted arithmetic mean: Mean Difference: “MIJ821 0.32 mg/kg biweekly” minus “placebo”.
    Comparison groups
    MIJ821 0.32 mg/kg biweekly v Placebo weekly
    Number of subjects included in analysis
    23
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2491
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3.06
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -8.86
         upper limit
    		 2.74

    Secondary: Change from baseline in the Young Mania Rating Scale

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    End point title
    		 Change from baseline in the Young Mania Rating Scale
    End point description
    To assess risk of mania induction. The Young Mania Rating Scale has 11 items and is based on the patient's subjective report of his/her clinical condition over the previous 48 hours. There are 4 items that are scored from 0 to 8 (irritability, speech, thought content, and disruptive/aggressive behavior) and the remaining items are scored from 0 to 4. Higher scores indicate more severe mania. The total clinical score was calculated as the summation of the individual subscale scores. The maximum for the total YMRS score is 60. The range is 0 to 60 with the higher score indicating more severe symptoms. AMCfB = adjusted mean change from baseline
    End point type
    Secondary
    End point timeframe
    Baseline, 24 hours, and 6 weeks (day 43)
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    11
    10
    10
    9
    10
    20
    Units: Scores on a Scale
    least squares mean (standard error)
        AMCfB at 24 hrs (n=11,10,10,9,10,20)
    -1.41 ( 0.5 )
    -1.07 ( 0.5 )
    -1.66 ( 0.5 )
    -0.81 ( 0.5 )
    -1.56 ( 0.5 )
    -0.72 ( 0.3 )
        AMCfB at day 43 (n=8,8,8,6,9,17)
    -1.28 ( 0.6 )
    -2.13 ( 0.7 )
    -0.65 ( 0.7 )
    -1.55 ( 0.7 )
    -1.80 ( 0.7 )
    -0.92 ( 0.4 )
    No statistical analyses for this end point

    Secondary: Bech-Rafaelsen melancholia scale

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    End point title
    		 Bech-Rafaelsen melancholia scale
    End point description
    To assess efficacy in the melancholic subtype of depression. Depression scales are used primarily to measure changes, for example, to evaluate the efficacy of treatment with antidepressants. The Bech-Rafaelsen Melancholia Scale (BRMS) is a frequently used clinician rating scale to assess the severity of depression over the past 3 days. Each of the 11 BRMS items is operationally defined on a five-point scale (0-4); hence, the total score ranges from 0 to 44, higher scores indicating greater severity of depression.
    End point type
    Secondary
    End point timeframe
    24 hours, 48 hours and 6 weeks (Day 43)
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    11
    10
    10
    9
    10
    20
    Units: Scores on a Scale
    arithmetic mean (standard deviation)
        Change at 24 hrs (n=11,10,10,8,9,20)
    -11.9 ( 5.941 )
    -9.5 ( 4.625 )
    -7.9 ( 6.903 )
    -8.1 ( 4.612 )
    -7.7 ( 5.766 )
    -6.0 ( 5.262 )
        Change at 48 hrs (n=9,10,9,7,4,19)
    -9.9 ( 5.326 )
    -8.0 ( 5.185 )
    -7.6 ( 8.383 )
    -8.0 ( 5.508 )
    -12.5 ( 7.853 )
    -6.7 ( 6.659 )
        Change at day 43 (n=8,8,8,6,9,17)
    -8.6 ( 6.589 )
    -8.6 ( 5.423 )
    -7.6 ( 10.013 )
    -6.0 ( 9.338 )
    -8.9 ( 8.343 )
    -6.9 ( 5.988 )
    No statistical analyses for this end point

    Secondary: PK properties of MIJ821 in plasma - Cmax (ng/mL)

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    End point title
    		 PK properties of MIJ821 in plasma - Cmax (ng/mL)
    End point description
    To assess MIJ821 pharmacokinetics in plasma described by Cmax
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Pooled MIJ821 0.16 mg/kg Pooled MIJ821 0.32 mg/kg
    Number of subjects analysed
    14
    11
    Units: ng/mL
        arithmetic mean (standard deviation)
    99.5 ( 47.8 )
    149 ( 63.4 )
    No statistical analyses for this end point

    Secondary: PK properties of MIJ821 in plasma - Tmax (ng/mL)

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    End point title
    		 PK properties of MIJ821 in plasma - Tmax (ng/mL)
    End point description
    To assess MIJ821 pharmacokinetics in plasma described by Tmax
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Pooled MIJ821 0.16 mg/kg Pooled MIJ821 0.32 mg/kg
    Number of subjects analysed
    14
    11
    Units: hour
        median (full range (min-max))
    0.683 (0.650 to 0.700)
    0.667 (0.667 to 0.700)
    No statistical analyses for this end point

    Secondary: PK properties of MIJ821 in plasma - AUClast (h*ng/mL)

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    End point title
    		 PK properties of MIJ821 in plasma - AUClast (h*ng/mL)
    End point description
    To assess MIJ821 pharmacokinetics in plasma described by AUClast (h*ng/mL)
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Pooled MIJ821 0.16 mg/kg Pooled MIJ821 0.32 mg/kg
    Number of subjects analysed
    14
    11
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    496 ( 239 )
    738 ( 302 )
    No statistical analyses for this end point

    Secondary: PK properties of MIJ821 in plasma - AUC0-24h (h*ng/mL)

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    End point title
    		 PK properties of MIJ821 in plasma - AUC0-24h (h*ng/mL)
    End point description
    To assess MIJ821 pharmacokinetics in plasma described by AUC0-24h (h*ng/mL)
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Pooled MIJ821 0.16 mg/kg Pooled MIJ821 0.32 mg/kg
    Number of subjects analysed
    13
    11
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    462 ( 232 )
    713 ( 275 )
    No statistical analyses for this end point

    Secondary: Change from baseline in the CORE Melancholia Total Scale

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    End point title
    		 Change from baseline in the CORE Melancholia Total Scale
    End point description
    To assess efficacy in melancholic subtype of depression. This scale is an 18 item scale, with a 6 item component capturing cognitive impairment and two motoric scales capturing psychomotor retardation (7 items) and psychomotor agitation (5 items). A cut-off score of 8 or more has been shown to ifferentiate melancholic from non-melancholic depression, with higher scores representing a greater probability of melancholic depression. (Parker and McCraw 2017). The total clinical score was calculated as the summation of the individual subscale scores. The maximum for the total CORE Melancholia score is 54. The range is 0 to 54 with the higher score indicating more severe symptoms. AMCfB - adjusted mean change from baseline
    End point type
    Secondary
    End point timeframe
    Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    11
    10
    10
    9
    10
    20
    Units: Scores on a Scale
    least squares mean (standard error)
        AMCfB at 24 hrs (n=4,3,4,3,9,8)
    -4.76 ( 2.9 )
    -3.64 ( 3.6 )
    -3.93 ( 3.0 )
    1.38 ( 3.5 )
    -5.07 ( 2.0 )
    -3.61 ( 2.0 )
        AMCfB at 48 hrs (n=2,3,3,2,4,9)
    -5.77 ( 3.9 )
    -2.82 ( 3.7 )
    -5.92 ( 3.2 )
    1.62 ( 4.0 )
    -6.68 ( 2.6 )
    -5.06 ( 1.9 )
        AMCfB at day 43 (n=3,2,3,2,8,8)
    -5.79 ( 3.4 )
    -4.82 ( 4.4 )
    -7.24 ( 3.5 )
    -6.49 ( 4.3 )
    -9.01 ( 2.1 )
    -5.21 ( 2.1 )
    No statistical analyses for this end point

    Secondary: Summary of Adverse Events

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    End point title
    		 Summary of Adverse Events
    End point description
    Summary of Adverse Events
    End point type
    Secondary
    End point timeframe
    Adverse events were reported from first dose of study treatment until end of study treatment plus 30 post treatment, up to a maximum duration of 66 days.
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    11
    10
    10
    9
    10
    20
    Units: Participants
        AEs, subjects with AEs
    7
    6
    7
    6
    6
    7
        Study drug-related AEs
    5
    5
    7
    5
    6
    5
        SAEs
    0
    1
    0
    3
    0
    1
        AEs leading to disc.of study treatment
    1
    0
    0
    2
    0
    1
        Study drug-related AEs leading to disc.
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Clinician-Administered Dissociative States Scale

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    End point title
    		 Clinician-Administered Dissociative States Scale
    End point description
    To assess safety and tolerability, especially dissociative side effects. The Clinical-Administered Dissociative States Scale (CADSS) is a questionnaire that assesses dissociative effects. Each item is scored from 0 to 4 and individual scores are to be summed to obtain a total score ranging from a minimum of 0 to a maximum of 80. Higher scores represent a more severe condition.
    End point type
    Secondary
    End point timeframe
    Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    11
    10
    10
    9
    10
    20
    Units: Scores on a Scale
    arithmetic mean (standard deviation)
        Change at 24 hrs (n=11,10,10,8,10,20)
    1.09 ( 5.262 )
    1.10 ( 2.726 )
    2.10 ( 3.414 )
    3.00 ( 3.703 )
    -0.50 ( 0.707 )
    -0.25 ( 0.716 )
        Change at 48 hrs (n=9,10,9,7,4,19)
    -0.22 ( 0.667 )
    0.50 ( 2.369 )
    4.44 ( 10.394 )
    3.14 ( 3.976 )
    0.00 ( 0.00 )
    -0.16 ( 0.375 )
        Change at day 43 (n=8,8,8,6,9,17)
    0.00 ( 1.927 )
    0.00 ( 0.00 )
    0.38 ( 1.061 )
    1.00 ( 2.449 )
    0.00 ( 1.118 )
    -0.18 ( 0.636 )
    No statistical analyses for this end point

    Secondary: Change from baseline in the Dissociative Experiences Total Score

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    End point title
    		 Change from baseline in the Dissociative Experiences Total Score
    End point description
    The Dissociative Experiences Scale (DES) consists of twenty-eight questions about experiences the subject has experienced in his/her daily life. The subject determines to what degree he/she has been facing the situation by selecting a percentage from 0% (never) to 100% (always), with 10% increments in between. Higher scores mean higher severity. AMCfB = adjusted mean change from baseline
    End point type
    Secondary
    End point timeframe
    Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    11
    10
    10
    9
    10
    20
    Units: Scores on a Scale
    least squares mean (standard error)
        AMCfB at 24 hrs (n=11,10,10,9,10,20)
    1.82 ( 1.0 )
    2.00 ( 1.1 )
    1.20 ( 1.1 )
    7.22 ( 1.1 )
    2.10 ( 1.1 )
    2.50 ( 0.8 )
        AMCfB at 48 hrs (n=9,10,9,7,4,19)
    1.80 ( 1.1 )
    2.30 ( 1.1 )
    1.89 ( 1.1 )
    3.46 ( 1.2 )
    1.89 ( 1.4 )
    2.43 ( 0.8 )
        AMCfB at day 43 (n=8,8,8,6,9,17)
    1.38 ( 1.1 )
    1.61 ( 1.1 )
    1.02 ( 1.1 )
    0.24 ( 1.3 )
    1.86 ( 1.1 )
    2.63 ( 0.8 )
    No statistical analyses for this end point

    Secondary: Sheehan Suicidality Tracking Scale - (SSTS)

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    End point title
    		 Sheehan Suicidality Tracking Scale - (SSTS)
    End point description
    Sheehan suicidality tracking scale(S-STS) is a fourteen-item (up to 22) scale. Each item in the S-STS is scored on a 5-point Likert scale (0=not at all, 1= a little, 2=moderately, 3=very, and 4=extremely). Data from the S-STS will be analyzed as individual item scores, suicidal ideation subscale score (sum of scores from items 2, 3 and 4, plus score from item 5 if ≤1), suicidal behavior subscale score (sum of scores from items 6, 7a and 8, plus score from item 5 if >1). Higher scores represent a more severe condition. CfB = change from baseline
    End point type
    Secondary
    End point timeframe
    Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    11
    10
    10
    9
    10
    20
    Units: Scores on a Scale
    arithmetic mean (standard deviation)
        Suicidal behavior CfB at 24 hrs
    0.00 ( 0.00 )
    0.00 ( 0.00 )
    0.00 ( 0.00 )
    0.11 ( 0.333 )
    -0.10 ( 0.316 )
    0.00 ( 0.00 )
        Suicidal behavior CfB at 48 hrs (n=9,10,9,7,4,19)
    0.00 ( 0.00 )
    0.00 ( 0.00 )
    0.00 ( 0.00 )
    0.00 ( 0.00 )
    0.00 ( 0.00 )
    0.00 ( 0.00 )
        Suicidal behavior CfB at day 43 (n=8,8,8,6,9,17)
    0.00 ( 0.00 )
    0.00 ( 0.00 )
    0.00 ( 0.00 )
    0.00 ( 0.00 )
    -0.11 ( 0.333 )
    0.12 ( 0.485 )
        Suicidal ideation CfB at 24 hrs
    -0.45 ( 0.820 )
    -0.50 ( 0.850 )
    -0.30 ( 0.675 )
    0.11 ( 1.269 )
    -0.40 ( 0.966 )
    -0.20 ( 0.523 )
        Suicidal ideation CfB at 48 hrs (n=9,10,9,7,4,19)
    -0.22 ( 0.667 )
    -0.50 ( 0.850 )
    -0.33 ( 0.707 )
    -0.43 ( 0.787 )
    0.00 ( 0.00 )
    -0.16 ( 0.375 )
        Suicidal ideation CfB at day 43 (n=8,8,8,6,9,17)
    -0.38 ( 0.744 )
    -0.13 ( 0.354 )
    -0.13 ( 1.126 )
    0.00 ( 1.265 )
    -0.11 ( 1.269 )
    0.12 ( 1.111 )
        SSTS total CfB at 24 hrs
    -0.45 ( 0.820 )
    -0.50 ( 0.850 )
    -0.30 ( 0.675 )
    0.11 ( 1.764 )
    -0.50 ( 1.269 )
    -0.20 ( 0.523 )
        SSTS total CfB at 48 hrs (n=9,10,9,7,4,19)
    -0.22 ( 0.667 )
    -0.50 ( 0.850 )
    -0.33 ( 0.707 )
    -0.57 ( 1.134 )
    0.00 ( 0.00 )
    -0.16 ( 0.375 )
        SSTS total CfB at Day 43 (n=8,8,8,6,9,17)
    -0.38 ( 0.744 )
    -0.13 ( 0.354 )
    -0.13 ( 1.126 )
    -0.17 ( 1.602 )
    -0.22 ( 1.563 )
    0.47 ( 2.503 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants with treatment remissions (MADRS<7)

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    End point title
    		 Percentage of Participants with treatment remissions (MADRS<7)
    End point description
    Percentage of Participants with treatment remissions as assessed via (MADRS<7)
    End point type
    Secondary
    End point timeframe
    24 hours, 48 hours, and 6 weeks (Day 43)
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    11
    10
    10
    9
    10
    20
    Units: Percentage of Participants
    number (not applicable)
        at 24 hrs (n=11,10,10,8,10,20)
    9.1
    20.0
    0
    11.1
    20.0
    5.0
        at 48 hrs (n=9,10,9,7,4,19)
    22.2
    10.0
    11.1
    28.6
    25.0
    10.5
        at Day 43 (n=8,8,8,6, 9,17)
    25.0
    37.5
    0
    16.7
    22.2
    11.8
    No statistical analyses for this end point

    Secondary: Change from baseline in the Total Hamilton Anxiety Scale

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    End point title
    		 Change from baseline in the Total Hamilton Anxiety Scale
    End point description
    The Hamilton Anxiety Rating Scale (HAM-A) measures psychic anxiety and somatic anxiety symptoms based on a clinical assessment and patient interview. The scale has 14 items, with each item rated from 0-4, ranging from not present to very severe. A maximum score of 56 indicates the most severe case. (Hamilton 1959).
    End point type
    Secondary
    End point timeframe
    Baseline, and at 6 weeks (day 43)
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    8
    8
    8
    6
    8
    17
    Units: Scores on a Scale
        least squares mean (standard error)
    -1.94 ( 2.0 )
    -5.69 ( 2.0 )
    -7.17 ( 2.0 )
    -3.83 ( 2.2 )
    -4.93 ( 2.0 )
    -4.80 ( 1.4 )
    No statistical analyses for this end point

    Secondary: Summary statistics of total Hamilton Anxiety scale - change from baseline

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    End point title
    		 Summary statistics of total Hamilton Anxiety scale - change from baseline
    End point description
    The Hamilton Anxiety Rating Scale (HAM-A) measures psychic anxiety and somatic anxiety symptoms based on a clinical assessment and patient interview. The scale has 14 items, with each item rated from 0-4, ranging from not present to very severe. A maximum score of 56 indicates the most severe case. (Hamilton 1959).
    End point type
    Secondary
    End point timeframe
    Change from baseline at week 6 (Day 43)
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    8
    8
    8
    6
    8
    17
    Units: Scores on a Scale
        arithmetic mean (standard deviation)
    -2.6 ( 6.927 )
    -5.4 ( 4.565 )
    -6.8 ( 6.606 )
    -4.2 ( 9.432 )
    -5.4 ( 7.763 )
    -5.1 ( 5.651 )
    No statistical analyses for this end point

    Secondary: Change from baseline in the Total Koukopoulos Mixed Depression Rating Scale

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    End point title
    		 Change from baseline in the Total Koukopoulos Mixed Depression Rating Scale
    End point description
    The Koukopoulos Mixed Depression Rating Scale (KMDRS) assesses the excitatory or mixed nature in patients suffering from a Major Depressive Episode (MDE) as defined by DSM-5 criteria. This scale is meant to be used in conjunction with another scale that assess typical depression and anxiety symptoms. The scale contains 14 items to be evaluated by clinical assessment and patient interview on symptoms potentially experienced over the past week. Overall score increases with severity of symptoms and has a maximum score of 51. (Sani et al 2018). AMCfB = adjusted mean change from baseline
    End point type
    Secondary
    End point timeframe
    Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
    End point values
    		 MIJ821 0.16 mg/kg weekly MIJ821 0.16 mg/kg biweekly MIJ821 0.32 mg/kg weekly MIJ821 0.32 mg/kg biweekly Ketamine 0.5 mg/kg weekly Placebo weekly
    Number of subjects analysed
    11
    10
    10
    9
    10
    20
    Units: Scores on a Scale
    least squares mean (standard error)
        AMCfB at 24 hrs (n=11,10,10,9,10,20)
    -2.79 ( 0.9 )
    -2.38 ( 0.9 )
    -1.50 ( 1.0 )
    -2.46 ( 1.0 )
    -1.28 ( 1.0 )
    -2.33 ( 0.7 )
        AMCfB at 48 hrs (n=9,10,9,7,4,19)
    -2.95 ( 1.0 )
    -1.03 ( 0.9 )
    -1.97 ( 1.0 )
    -3.43 ( 1.1 )
    0.01 ( 1.3 )
    -1.97 ( 0.7 )
        AMCfB at day 43 (n=8,8,8,6,9,17)
    -1.18 ( 1.0 )
    -1.06 ( 1.0 )
    -1.55 ( 1.1 )
    -2.04 ( 1.2 )
    -1.68 ( 1.0 )
    -1.59 ( 0.7 )
    No statistical analyses for this end point

    Secondary: Responders (>50% improvement in Bech-Rafaelsen Melancholia scale) and Melancholia and Mixed Depression Checklist factor.

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    End point title
    		 Responders (>50% improvement in Bech-Rafaelsen Melancholia scale) and Melancholia and Mixed Depression Checklist factor.
    End point description
    Percentage of Participants who responded. The first mixed depression checklist, created by Koukopoulos, has 8 criteria, which are marked as present or absent. If 3 or more criteria are marked present, then mixed depression would be diagnosed. The second mixed depression checklist, created by Angst, lists the 7 criteria for mania from DSM-5, which are marked as present or absent. If 3 or more criteria are marked present, excluding any duration criterion, then mixed depression would be diagnosed. The melancholia checklist, created by Ghaemi for this study, has 4 criteria, which are marked as present or absent. If 3 or more criteria are marked present, then melancholia would be diagnosed.
    End point type
    Secondary
    End point timeframe
    24 hours, 48 hours, and 6 weeks (Day 43)
    End point values
    		 Koukopoulos Angst Ghaemi
    Number of subjects analysed
    9
    9
    9
    Units: Percentage of Participants
    number (not applicable)
        % who responded at 24 hrs - drugs (n=5,5,5)
    40.0
    0
    20.0
        % who responded at 24 hrs - placebo (n=1,1,1)
    0
    0
    100
        % who responded at 48 hrs - drugs (N=6, 6, 6)
    50.0
    0
    33.3
        % who responded at 48 hrs - placebo (n=2,2,2)
    0
    0
    50.0
        % who responded at Day 43 - drugs (n=9,9,9)
    55.6
    0
    44.4
        % who responded at Day 43- placebo (n=3,3,3)
    33.3
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from first dose of study treatment until end of study treatment plus 30 post treatment, up to a maximum duration of 66 days.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    MIJ821 0.16 mg/kg weekly*
    Reporting group description
    		 MIJ821 0.16 mg/kg weekly*

    Reporting group title
    MIJ821 0.32 mg/kg weekly
    Reporting group description
    		 MIJ821 0.32 mg/kg weekly

    Reporting group title
    MIJ821 0.16 mg/kg every other week
    Reporting group description
    		 MIJ821 0.16 mg/kg every other week

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Reporting group title
    Ketamine
    Reporting group description
    		 Ketamine

    Reporting group title
    Total
    Reporting group description
    		 Total

    Reporting group title
    MIJ821 0.32 mg/kg every other week
    Reporting group description
    		 MIJ821 0.32 mg/kg every other week

    Serious adverse events
    		 MIJ821 0.16 mg/kg weekly* MIJ821 0.32 mg/kg weekly MIJ821 0.16 mg/kg every other week Placebo Ketamine Total MIJ821 0.32 mg/kg every other week
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 20 (5.00%)
    0 / 10 (0.00%)
    5 / 70 (7.14%)
    3 / 9 (33.33%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Major depression
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide threat
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MIJ821 0.16 mg/kg weekly* MIJ821 0.32 mg/kg weekly MIJ821 0.16 mg/kg every other week Placebo Ketamine Total MIJ821 0.32 mg/kg every other week
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 11 (63.64%)
    7 / 10 (70.00%)
    6 / 10 (60.00%)
    5 / 20 (25.00%)
    6 / 10 (60.00%)
    37 / 70 (52.86%)
    6 / 9 (66.67%)
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 10 (10.00%)
    5 / 70 (7.14%)
    1 / 9 (11.11%)
         occurrences all number
    0
    4
    0
    1
    1
    7
    1
    Feeling abnormal
         subjects affected / exposed
    3 / 11 (27.27%)
    2 / 10 (20.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    6 / 70 (8.57%)
    0 / 9 (0.00%)
         occurrences all number
    4
    8
    1
    0
    0
    13
    0
    Feeling of relaxation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Gait disturbance
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    0
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    Agitation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Anxiety
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    2 / 70 (2.86%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    1
    Confusional state
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 10 (0.00%)
    3 / 70 (4.29%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    0
    1
    0
    3
    1
    Daydreaming
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    2
    Depersonalisation/derealisation disorder
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    5 / 10 (50.00%)
    5 / 70 (7.14%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    22
    22
    0
    Disinhibition
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    6
    6
    0
    Dissociation
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 10 (0.00%)
    3 / 70 (4.29%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    3
    0
    Dissociative amnesia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Euphoric mood
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Illusion
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    2 / 70 (2.86%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    2
    0
    Insomnia
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 10 (0.00%)
    3 / 70 (4.29%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    3
    0
    Irritability
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Mood swings
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Sleep disorder
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Sleep terror
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Time perception altered
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    2 / 70 (2.86%)
    0 / 9 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    3
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Blood potassium decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Blood pressure increased
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    3 / 70 (4.29%)
    0 / 9 (0.00%)
         occurrences all number
    6
    0
    3
    0
    0
    9
    0
    Blood pressure systolic increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Injury, poisoning and procedural complications
    Poisoning deliberate
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Nervous system disorders
    Akathisia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Amnesia
         subjects affected / exposed
    2 / 11 (18.18%)
    5 / 10 (50.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    10 / 70 (14.29%)
    3 / 9 (33.33%)
         occurrences all number
    5
    11
    0
    0
    0
    24
    8
    Ataxia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    3 / 70 (4.29%)
    2 / 9 (22.22%)
         occurrences all number
    0
    3
    0
    0
    0
    9
    6
    Disturbance in attention
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    Dizziness
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    3 / 10 (30.00%)
    1 / 20 (5.00%)
    2 / 10 (20.00%)
    10 / 70 (14.29%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    3
    2
    5
    14
    1
    Dysarthria
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Dysgeusia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Headache
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 10 (10.00%)
    6 / 70 (8.57%)
    1 / 9 (11.11%)
         occurrences all number
    1
    4
    0
    1
    1
    8
    1
    Hypoaesthesia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 20 (5.00%)
    0 / 10 (0.00%)
    2 / 70 (2.86%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    3
    0
    Memory impairment
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    3 / 70 (4.29%)
    0 / 9 (0.00%)
         occurrences all number
    3
    1
    0
    0
    0
    4
    0
    Paraesthesia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    1 / 10 (10.00%)
    3 / 70 (4.29%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    2
    5
    8
    0
    Sciatica
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Somnolence
         subjects affected / exposed
    2 / 11 (18.18%)
    4 / 10 (40.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    8 / 70 (11.43%)
    0 / 9 (0.00%)
         occurrences all number
    2
    9
    1
    0
    2
    14
    0
    Syncope
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Tunnel vision
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Ear and labyrinth disorders
    Hyperacusis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    2 / 10 (20.00%)
    2 / 70 (2.86%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    3
    0
    Eye disorders
    Asthenopia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Photophobia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Dry mouth
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    3 / 10 (30.00%)
    4 / 70 (5.71%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    4
    5
    0
    Dyspepsia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    Frequent bowel movements
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    2 / 10 (20.00%)
    4 / 70 (5.71%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    1
    0
    6
    8
    0
    Vomiting
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 10 (10.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Oral herpes
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 10 (0.00%)
    1 / 70 (1.43%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 May 2019
    Amendment 01
    02 Jul 2019
    Amendment 02

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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