Proof of Concept Study Evaluating the Efficacy and Safety... | NCT03756129 | Trialant
NCT03756129
Sponsor
Novartis Pharmaceuticals
Status
Completed
Last Update Posted
Oct 8, 2021Actual
Enrollment
70Actual
Phase
Phase 2
Conditions
Depressive Disorder, Treatment-Resistant
Interventions
MIJ821
Placebo
Ketamine
Countries
United States
Spain
Protocol Section
Identification Module
NCT ID
NCT03756129
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CMIJ821X2201
Secondary IDs
Not provided
Brief Title
Proof of Concept Study Evaluating the Efficacy and Safety of MIJ821 in Patients With Treatment-resistant Depression
Official Title
A Multi-center, Randomized, subject-and Investigator Blinded, Placebo-controlled, Active Comparator, Parallel-group Proof of Concept Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of MIJ821 in Patients With Treatment-resistant Depression
Acronym
Not provided
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Oct 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 8, 2019Actual
Primary Completion Date
Mar 23, 2020Actual
Completion Date
Mar 23, 2020Actual
First Submitted Date
Nov 13, 2018
First Submission Date that Met QC Criteria
Nov 26, 2018
First Posted Date
Nov 28, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Feb 15, 2021
Results First Submitted that Met QC Criteria
Apr 28, 2021
Results First Posted Date
May 19, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 7, 2021
Last Update Posted Date
Oct 8, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study evaluated the efficacy and safety of the compound MIJ821 compared to placebo in patients aged from 18 to 65 years diagnosed with treatment-resistant depression. The study was conducted in the US and in Europe (Spain). The MIJ821 was administered via infusion on a weekly or bi-weekly basis. The efficacy was measured after 24 hours using a specific golden standard scale, the Montgomery-Asberg Depression Rating Scale. The study duration was 6 weeks of treatment plus 1 month of follow up period.
Detailed Description
This was a non-confirmatory, multi-center, 6-treatment arm in European (Spain) and 5-treatment arm in the US (no ketamine arm), randomized, subject and investigator blinded, parallel-group, placebo-controlled study in patients with treatment-resistant depression. The total duration for each subject in the study was maximum 14 weeks: a screening period of maximum 4 weeks, a 36-day treatment period and a 5-week follow-up period.
Conditions Module
Conditions
Depressive Disorder, Treatment-Resistant
Keywords
Refractory Depression
Therapy-Resistant Depression
Treatment Resistant Depression
MDE
MDD
Major depressive disorder (MDD)
clinical depression
major depression
unipolar depression
unipolar mood disorder
depression
the blues
mood disorder
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
70Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
MIJ821 low dose weekly
Experimental
Infusion. MIJ821 low dose weekly - 0.16 mg/kg
Drug: MIJ821
MIJ821 low dose bi-weekly
Experimental
Infusion. MIJ821 low dose bi-weekly - 0.16 mg/kg
Drug: MIJ821
MIJ821 high dose weekly
Experimental
Infusion. MIJ821 high dose weekly - 0.32 mg/kg
Drug: MIJ821
MIJ821 high dose bi-weekly
Experimental
Infusion. MIJ821 high dose bi-weekly - 0.32 mg/kg
Drug: MIJ821
Placebo weekly
Placebo Comparator
Infusion. Placebo weekly
Drug: Placebo
Ketamine 0.5 mg/kg weekly
Active Comparator
Infusion. Ketamine 0.5 mg/kg weekly
Interventions
Name
Type
Description
Arm Group Labels
Other Names
MIJ821
Drug
Different dosages and different regimen for MIJ821
MIJ821 high dose bi-weekly
MIJ821 high dose weekly
MIJ821 low dose bi-weekly
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs
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.
Baseline, and at 24 hours
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key Inclusion Criteria:
Signed informed consent.
Male and female subjects, 18 to 65 years of age (inclusive) at screening.
SCID-based DSM-5 defined major depressive episode at the time of screening
Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 24 at screening and baseline
Failure to respond to two or more antidepressant treatments, where two failed treatments are of two different antidepressants and at least one of which is in the current depressive episode, with adequate dose and duration (≥ 8 weeks duration, doses defined per agent), as identified by the Maudsley Treatment Inventory, and prior psychiatric history, assessed by the investigator, and further documented by medical records and/or third party report (family, friends, clinician-treaters) where available
If patients are taking any type of psychotropic drugs, a stable dose of psychotropic drugs at screening is defined as no changes in dose or type of antidepressants, antipsychotics, or mood stabilizers for at least 2 weeks prior to screening, if applicable.
No new antidepressant initiated 4 weeks or less before baseline, and 6 weeks or less before baseline if subject is initiated on fluoxetine
At least one prior clinical depressive episode (recurrent major depressive disorder), as identified by prior psychiatric history assessed by the investigator, and further documented by medical records and third party report (family, friends, clinician-treaters) where available.
Able to communicate well, and to understand and comply with study requirements
Key Exclusion Criteria:
Any current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder at screening.
Current alcohol or substance use disorder (including marijuana and prescribed amphetamine)) meeting DSM-5 criteria, within the past month at baseline. Nicotine and caffeine use disorders will not be considered as exclusionary.
Prior suicidality caused by or associated with ketamine, as identified by prior psychiatric history assessed by the investigator, and augmented by medical records and third party report (family, friends, clinician-treaters) where available.
Acute serious and/or imminent suicidal ideation and/or intent within the prior 2 weeks, or any suicide attempt within the prior 4 weeks at screening. Mild to moderate suicidal ideation, using the Sheehan Suicidal Ideation Scale and not meeting the above definition, is not an exclusion criterion.
Use of other investigational drugs within 30 days or 5 half-lives of randomization, whichever was longer; or longer if required by local regulations at baseline
Current pregnancy or lactation.
Positive HIV, Hepatitis B or C test.
Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment baseline
History of multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study.
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 3 years, regardless of whether there is evidence of local recurrence or metastases.
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug.
History of hypersensitivity to any of the study treatments or excipients or to drugs similar to chemical classes that affect NMDA receptor.
Current diagnosis of borderline personality disorder or antisocial personality disorder, based on DSM-5 criteria.
Current acute depressive episode lasting longer than two years continuously, defined as no two week or longer period where depressive symptoms are subsyndromal in severity for a full DSM-5 acute major depressive episode.
Considered by the investigator, for any other reason, to be an unsuitable candidate for the study.
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This is a non-confirmatory, multi-center, 6-treatment arm in the EU countries and 5-treatment arm in the USA (no ketamine arm), randomized, subject and investigator blinded, parallel group, placebo controlled study in treatment-resistant depression patients. The study allows for the inclusion of subjects seeking treatment for their disease from both an 'inpatient' or 'outpatient' clinic setting.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Drug: Ketamine
MIJ821 low dose weekly
Placebo
Drug
Infusion
Placebo weekly
Ketamine
Drug
Infusion
Ketamine 0.5 mg/kg weekly
Ketamine dose to be capped at 40 mg/day for patients over 80 kg
Baseline, and at 48 hours
Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6
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.
Baseline, and at Week 6
Change From Baseline in the Young Mania Rating Scale
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.
Baseline, 24 hours, and 6 weeks (day 43)
Bech-Rafaelsen Melancholia Scale
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.
Baseline, 24 hours, 48 hours and 6 weeks (Day 43)
PK Properties of MIJ821 in Plasma - Cmax (ng/mL)
To assess MIJ821 pharmacokinetics in plasma described by Cmax. A single, sparse PK measurement was taken on Day 1.
Day 1
PK Properties of MIJ821 in Plasma - Tmax (ng/mL)
To assess MIJ821 pharmacokinetics in plasma described by Tmax. A single, sparse PK measurement was taken on Day 1.
Day 1
PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL)
To assess MIJ821 pharmacokinetics in plasma described by AUClast (h*ng/mL). A single, sparse PK measurement was taken on Day 1.
Day 1
PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL)
To assess MIJ821 pharmacokinetics in plasma described by AUC0-24h (h*ng/mL). A single, sparse PK measurement was taken on Day 1.
Day 1
Change From Baseline in the CORE Melancholia Total Scale
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.
Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
Summary of Adverse Events
Summary of 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.
Clinician-Administered Dissociative States Scale
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.
Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
Change From Baseline in the Dissociative Experiences Total Score
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.
Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
Sheehan Suicidality Tracking Scale - (SSTS)
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.
Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
Percentage of Participants With Treatment Remissions (MADRS<7)
Percentage of Participants with treatment remissions as assessed via (MADRS<7)
24 hours, 48 hours, and 6 weeks (Day 43)
Change From Baseline in the Total Hamilton Anxiety Scale
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).
Baseline, and at 6 weeks (day 43)
Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline
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).
Change from baseline at week 6 (Day 43)
Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale
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).
Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor.
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.
24 hours, 48 hours, and 6 weeks (Day 43)
Garden Grove
California
92845
United States
Novartis Investigative Site
Oakland
California
94607
United States
Novartis Investigative Site
Bradenton
Florida
34201
United States
Novartis Investigative Site
Atlanta
Georgia
30331
United States
Novartis Investigative Site
Skokie
Illinois
60076
United States
Novartis Investigative Site
Rockville
Maryland
20850
United States
Novartis Investigative Site
Berlin
New Jersey
08009
United States
Novartis Investigative Site
Palma de Mallorca
Balearic Islands
07120
Spain
Novartis Investigative Site
Vitoria-Gasteiz
Basque Country
01004
Spain
Novartis Investigative Site
Barcelona
Catalonia
08036
Spain
Novartis Investigative Site
Barcelona
08006
Spain
FG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
FG003
MIJ821 0.32 mg/kg Biweekly
MIJ821 0.32 mg/kg biweekly
FG004
Ketamine 0.5 mg/kg Weekly
Ketamine 0.5 mg/kg weekly
FG005
Placebo Weekly
Placebo weekly
FG00011 subjects
FG00110 subjects
FG00210 subjects
FG0039 subjects1 participant in this group was randomized but not treated, and is not included in this data set.
FG00410 subjects1 participant in this group was randomized but not treated, and is not included in this data set.
FG00520 subjects
COMPLETED
FG0008 subjects
FG0018 subjects
FG0027 subjects
FG0036 subjects
FG0049 subjects
FG00515 subjects
NOT COMPLETED
FG0003 subjects
FG0012 subjects
FG0023 subjects
FG0033 subjects
FG0041 subjects
FG0055 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0032 subjects
FG0040 subjects
FG0050 subjects
Withdrawal by Subject
FG0002 subjects
FG0011 subjects
FG0023 subjects
FG0031 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
BG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
BG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
BG003
MIJ821 0.32 mg/kg Biweekly
MIJ821 0.32 mg/kg biweekly
BG004
Ketamine 0.5 mg/kg Weekly
Ketamine 0.5 mg/kg weekly
BG005
Placebo Weekly
Placebo weekly
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00011
BG00110
BG00210
BG0039
BG00410
BG00520
BG00670
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00048.6± 11.70
BG00153.7± 9.33
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0002
BG0015
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs
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.
Intent to Treat analysis set
Posted
Least Squares Mean
Standard Error
Scores on a Scale
Baseline, and at 24 hours
ID
Title
Description
OG000
Pooled MIJ821 0.16 mg/kg
Pooled MIJ821 0.16 mg/kg
OG001
Pooled MIJ821 0.32 mg/kg
Pooled MIJ821 0.32 mg/kg
OG002
Ketamine 0.5 mg/kg Weekly
Ketamine 0.5 mg/kg weekly
OG003
Placebo Weekly
Placebo weekly
Units
Counts
Participants
OG00021
OG00119
OG00210
OG003
Title
Denominators
Categories
Title
Measurements
OG000-15.51± 1.9
OG001-12.98± 1.9
OG002-12.94± 2.7
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Comparison of adjusted arithmetic mean: Mean Difference: "Pooled MIJ821 0.16 mg/kg" minus "placebo". The MIJ821 treatment arms vs placebo are primary.
ANCOVA
0.0013
Median Difference (Net)
-8.25
2-Sided
80
-11.67
-4.83
Superiority
OG001
OG003
Comparison of adjusted arithmetic mean: Mean Difference: "Pooled MIJ821 0.32 mg/kg" minus "placebo". The MIJ821 treatment arms vs placebo are primary.
Secondary
Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs
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.
Intent to Treat analysis set. Please note that some participants missed some visits in the study, and thus data for this outcome measure were not collected for some participants.
Posted
Least Squares Mean
Standard Error
Scores on a Scale
Baseline, and at 48 hours
ID
Title
Description
OG000
Pooled MIJ821 0.16 mg/kg
Pooled MIJ821 0.16 mg/kg
OG001
Pooled MIJ821 0.32 mg/kg
Pooled MIJ821 0.32 mg/kg
OG002
Ketamine 0.5 mg/kg Weekly
Ketamine 0.5 mg/kg weekly
Secondary
Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6
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.
Intent to Treat analysis set
Posted
Least Squares Mean
Standard Error
Scores on a Scale
Baseline, and at Week 6
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
OG003
MIJ821 0.32 mg/kg Biweekly
Secondary
Change From Baseline in the Young Mania Rating Scale
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.
Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
Posted
Least Squares Mean
Standard Error
Scores on a Scale
Baseline, 24 hours, and 6 weeks (day 43)
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
Secondary
Bech-Rafaelsen Melancholia Scale
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.
Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
Posted
Mean
Standard Deviation
Scores on a Scale
Baseline, 24 hours, 48 hours and 6 weeks (Day 43)
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
OG003
MIJ821 0.32 mg/kg Biweekly
Secondary
PK Properties of MIJ821 in Plasma - Cmax (ng/mL)
To assess MIJ821 pharmacokinetics in plasma described by Cmax. A single, sparse PK measurement was taken on Day 1.
PK analysis set
Posted
Mean
Standard Deviation
ng/mL
Day 1
ID
Title
Description
OG000
Pooled MIJ821 0.16 mg/kg
Pooled MIJ821 0.16 mg/kg
OG001
Pooled MIJ821 0.32 mg/kg
Pooled MIJ821 0.32 mg/kg
Units
Counts
Participants
OG000
Secondary
PK Properties of MIJ821 in Plasma - Tmax (ng/mL)
To assess MIJ821 pharmacokinetics in plasma described by Tmax. A single, sparse PK measurement was taken on Day 1.
PK analysis set
Posted
Median
Full Range
hour
Day 1
ID
Title
Description
OG000
Pooled MIJ821 0.16 mg/kg
Pooled MIJ821 0.16 mg/kg
OG001
Pooled MIJ821 0.32 mg/kg
Pooled MIJ821 0.32 mg/kg
Units
Counts
Participants
OG000
Secondary
PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL)
To assess MIJ821 pharmacokinetics in plasma described by AUClast (h*ng/mL). A single, sparse PK measurement was taken on Day 1.
PK analysis set
Posted
Mean
Standard Deviation
h*ng/mL
Day 1
ID
Title
Description
OG000
Pooled MIJ821 0.16 mg/kg
Pooled MIJ821 0.16 mg/kg
OG001
Pooled MIJ821 0.32 mg/kg
Pooled MIJ821 0.32 mg/kg
Units
Counts
Participants
OG000
Secondary
PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL)
To assess MIJ821 pharmacokinetics in plasma described by AUC0-24h (h*ng/mL). A single, sparse PK measurement was taken on Day 1.
PK analysis set
Posted
Mean
Standard Deviation
h*ng/mL
Day 1
ID
Title
Description
OG000
Pooled MIJ821 0.16 mg/kg
Pooled MIJ821 0.16 mg/kg
OG001
Pooled MIJ821 0.32 mg/kg
Pooled MIJ821 0.32 mg/kg
Units
Counts
Participants
OG000
Secondary
Change From Baseline in the CORE Melancholia Total Scale
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.
Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
Posted
Least Squares Mean
Standard Error
Scores on a Scale
Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
Secondary
Summary of Adverse Events
Summary of Adverse Events
safety analysis set
Posted
Count of Participants
Participants
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.
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
OG003
MIJ821 0.32 mg/kg Biweekly
MIJ821 0.32 mg/kg biweekly
OG004
Ketamine 0.5 mg/kg Weekly
Ketamine 0.5 mg/kg weekly
Secondary
Clinician-Administered Dissociative States Scale
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.
Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
Posted
Mean
Standard Deviation
Scores on a Scale
Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
OG003
MIJ821 0.32 mg/kg Biweekly
MIJ821 0.32 mg/kg biweekly
Secondary
Change From Baseline in the Dissociative Experiences Total Score
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.
Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
Posted
Least Squares Mean
Standard Error
Scores on a Scale
Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
OG003
MIJ821 0.32 mg/kg Biweekly
MIJ821 0.32 mg/kg biweekly
Secondary
Sheehan Suicidality Tracking Scale - (SSTS)
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.
Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
Posted
Mean
Standard Deviation
Scores on a Scale
Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
OG003
MIJ821 0.32 mg/kg Biweekly
Secondary
Percentage of Participants With Treatment Remissions (MADRS<7)
Percentage of Participants with treatment remissions as assessed via (MADRS<7)
Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
Posted
Number
Percentage of Participants
24 hours, 48 hours, and 6 weeks (Day 43)
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
OG003
MIJ821 0.32 mg/kg Biweekly
MIJ821 0.32 mg/kg biweekly
OG004
Ketamine 0.5 mg/kg Weekly
Ketamine 0.5 mg/kg weekly
Secondary
Change From Baseline in the Total Hamilton Anxiety Scale
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).
Intent-to-treat analysis set
Posted
Least Squares Mean
Standard Error
Scores on a Scale
Baseline, and at 6 weeks (day 43)
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
OG003
MIJ821 0.32 mg/kg Biweekly
MIJ821 0.32 mg/kg biweekly
OG004
Ketamine 0.5 mg/kg Weekly
Secondary
Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline
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).
Intent-to-treat analysis set
Posted
Mean
Standard Deviation
Scores on a Scale
Change from baseline at week 6 (Day 43)
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
OG003
MIJ821 0.32 mg/kg Biweekly
MIJ821 0.32 mg/kg biweekly
OG004
Ketamine 0.5 mg/kg Weekly
Secondary
Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale
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).
Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
Posted
Least Squares Mean
Standard Error
Scores on a Scale
Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
ID
Title
Description
OG000
MIJ821 0.16 mg/kg Weekly
MIJ821 0.16 mg/kg weekly
OG001
MIJ821 0.16 mg/kg Biweekly
MIJ821 0.16 mg/kg biweekly
OG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
OG003
Secondary
Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor.
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.
Intent-to-treat analysis set. The sampling size for this outcome measure was too small to support inferential statistics; therefore, the results for this outcome measure were limited to this high-level summary table, where data for the 2 drugs were pooled (MIJ821, all doses and all dosage regimes) and Ketamine vs placebo.
Posted
Number
Percentage of Participants
24 hours, 48 hours, and 6 weeks (Day 43)
ID
Title
Description
OG000
Koukopoulos
Koukopoulos Mixed Depression Rating Scale
OG001
Angst
Mixed depression checklist, created by Angst
Time Frame
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.
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
MIJ821 0.16 mg/kg Weekly*
MIJ821 0.16 mg/kg weekly*
0
11
0
11
7
11
EG001
MIJ821 0.16 mg/kg Every Other Week
MIJ821 0.16 mg/kg every other week
0
10
1
10
6
10
EG002
MIJ821 0.32 mg/kg Weekly
MIJ821 0.32 mg/kg weekly
0
10
0
10
7
10
EG003
MIJ821 0.32 mg/kg Every Other Week
MIJ821 0.32 mg/kg every other week
0
9
3
9
6
9
EG004
Ketamine 0.5 mg/kg Weekly
Ketamine 0.5 mg/kg weekly
0
10
0
10
6
10
EG005
Placebo Weekly
Placebo weekly
0
20
1
20
5
20
EG006
Total
Total
0
70
5
70
37
70
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Atrial fibrillation
Cardiac disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG0031 affected9 at risk
EG0040 affected10 at risk
EG0050 affected20 at risk
EG0061 affected70 at risk
Major depression
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Suicide attempt
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Suicide threat
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected10 at risk
EG0020 affected10 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Angina pectoris
Cardiac disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG0031 affected9 at risk
EG0040 affected10 at risk
EG0050 affected20 at risk
EG0061 affected70 at risk
Hyperacusis
Ear and labyrinth disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Asthenopia
Eye disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Photophobia
Eye disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Vision blurred
Eye disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected10 at risk
EG0020 affected10 at risk
EG003
Frequent bowel movements
Gastrointestinal disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected10 at risk
EG0020 affected10 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected10 at risk
EG0021 affected10 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Fatigue
General disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0022 affected10 at risk
EG003
Feeling abnormal
General disorders
MedDRA (22.1)
Systematic Assessment
EG0003 affected11 at risk
EG0011 affected10 at risk
EG0022 affected10 at risk
EG003
Feeling of relaxation
General disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Gait disturbance
General disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Oral herpes
Infections and infestations
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Poisoning deliberate
Injury, poisoning and procedural complications
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Blood potassium decreased
Investigations
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Blood pressure increased
Investigations
MedDRA (22.1)
Systematic Assessment
EG0002 affected11 at risk
EG0011 affected10 at risk
EG0020 affected10 at risk
EG003
Blood pressure systolic increased
Investigations
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Platelet count decreased
Investigations
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected10 at risk
EG0020 affected10 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Akathisia
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Amnesia
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0002 affected11 at risk
EG0010 affected10 at risk
EG0025 affected10 at risk
EG003
Ataxia
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Disturbance in attention
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected10 at risk
EG0020 affected10 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0002 affected11 at risk
EG0013 affected10 at risk
EG0021 affected10 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Headache
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0022 affected10 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected10 at risk
EG0020 affected10 at risk
EG003
Memory impairment
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0002 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Sciatica
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0002 affected11 at risk
EG0011 affected10 at risk
EG0024 affected10 at risk
EG003
Syncope
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Tunnel vision
Nervous system disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Abnormal dreams
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected10 at risk
EG0020 affected10 at risk
EG003
Agitation
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Daydreaming
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Depersonalisation/derealisation disorder
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Disinhibition
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Dissociation
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0002 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Dissociative amnesia
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Euphoric mood
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Illusion
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0011 affected10 at risk
EG0020 affected10 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0002 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Irritability
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Mood swings
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Sleep terror
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Time perception altered
Psychiatric disorders
MedDRA (22.1)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0021 affected10 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (22.1)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected10 at risk
EG0020 affected10 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.