Depressive Disorder, Treatment-Resistant
Conditions
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
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.
Interventions
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs | Baseline, and at 24 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6 | Baseline, and 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. |
| Change From Baseline in the Young Mania Rating Scale | Baseline, 24 hours, and 6 weeks (day 43) | 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. |
| Bech-Rafaelsen Melancholia Scale | Baseline, 24 hours, 48 hours and 6 weeks (Day 43) | 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. |
| PK Properties of MIJ821 in Plasma - Cmax (ng/mL) | Day 1 | To assess MIJ821 pharmacokinetics in plasma described by Cmax. A single, sparse PK measurement was taken on Day 1. |
| PK Properties of MIJ821 in Plasma - Tmax (ng/mL) | Day 1 | To assess MIJ821 pharmacokinetics in plasma described by Tmax. A single, sparse PK measurement was taken on Day 1. |
| PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL) | Day 1 | To assess MIJ821 pharmacokinetics in plasma described by AUClast (h\*ng/mL). A single, sparse PK measurement was taken on Day 1. |
| PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL) | Day 1 | To assess MIJ821 pharmacokinetics in plasma described by AUC0-24h (h\*ng/mL). A single, sparse PK measurement was taken on Day 1. |
| Change From Baseline in the CORE Melancholia Total Scale | Baseline, 24 hours, 48 hrs, and 6 weeks (day 43) | 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. |
| Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs | Baseline, and at 48 hours | 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. |
| Clinician-Administered Dissociative States Scale | Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43) | 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 in the Dissociative Experiences Total Score | Baseline, 24 hours, 48 hrs, and 6 weeks (day 43) | 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. |
| Sheehan Suicidality Tracking Scale - (SSTS) | Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43) | 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. |
| Percentage of Participants With Treatment Remissions (MADRS<7) | 24 hours, 48 hours, and 6 weeks (Day 43) | Percentage of Participants with treatment remissions as assessed via (MADRS\<7) |
| Change From Baseline in the Total Hamilton Anxiety Scale | Baseline, and at 6 weeks (day 43) | 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). |
| Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline | Change from baseline at week 6 (Day 43) | 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 in the Total Koukopoulos Mixed Depression Rating Scale | Baseline, 24 hours, 48 hrs, and 6 weeks (day 43) | 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). |
| Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | 24 hours, 48 hours, and 6 weeks (Day 43) | 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. |
| 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. | Summary of Adverse Events |
Countries
Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MIJ821 0.16 mg/kg Weekly MIJ821 0.16 mg/kg weekly | 11 |
| MIJ821 0.16 mg/kg Biweekly MIJ821 0.16 mg/kg biweekly | 10 |
| MIJ821 0.32 mg/kg Weekly MIJ821 0.32 mg/kg weekly | 10 |
| MIJ821 0.32 mg/kg Biweekly MIJ821 0.32 mg/kg biweekly | 9 |
| Ketamine 0.5 mg/kg Weekly Ketamine 0.5 mg/kg weekly | 10 |
| Placebo Weekly Placebo weekly | 20 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 3 | 1 | 1 | 3 |
Baseline characteristics
| Characteristic | MIJ821 0.16 mg/kg Biweekly | MIJ821 0.32 mg/kg Weekly | MIJ821 0.32 mg/kg Biweekly | MIJ821 0.16 mg/kg Weekly | Ketamine 0.5 mg/kg Weekly | Placebo Weekly | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 10 Participants | 9 Participants | 11 Participants | 10 Participants | 20 Participants | 69 Participants |
| Age, Continuous | 53.7 Years STANDARD_DEVIATION 9.33 | 42.9 Years STANDARD_DEVIATION 14.47 | 46.6 Years STANDARD_DEVIATION 11.83 | 48.6 Years STANDARD_DEVIATION 11.7 | 52.3 Years STANDARD_DEVIATION 6.96 | 44.8 Years STANDARD_DEVIATION 10.69 | 47.7 Years STANDARD_DEVIATION 11.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 8 Participants | 3 Participants | 0 Participants | 10 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 1 Participants | 8 Participants | 9 Participants | 9 Participants | 39 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 6 Participants | 2 Participants | 7 Participants | 9 Participants | 35 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 3 Participants | 9 Participants | 3 Participants | 11 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 | 0 / 10 | 0 / 9 | 0 / 10 | 0 / 20 | 0 / 70 |
| other Total, other adverse events | 7 / 11 | 6 / 10 | 7 / 10 | 6 / 9 | 6 / 10 | 5 / 20 | 37 / 70 |
| serious Total, serious adverse events | 0 / 11 | 1 / 10 | 0 / 10 | 3 / 9 | 0 / 10 | 1 / 20 | 5 / 70 |
Outcome results
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.
Time frame: Baseline, and at 24 hours
Population: Intent to Treat analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs | -15.51 Scores on a Scale | Standard Error 1.9 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs | -12.98 Scores on a Scale | Standard Error 1.9 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs | -12.94 Scores on a Scale | Standard Error 2.7 |
| Placebo Weekly | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs | -7.27 Scores on a Scale | Standard Error 1.9 |
Comparison: Comparison of adjusted arithmetic mean: Mean Difference: Pooled MIJ821 0.16 mg/kg minus placebo. The MIJ821 treatment arms vs placebo are primary.p-value: 0.001380% CI: [-11.67, -4.83]ANCOVA
Comparison: Comparison of adjusted arithmetic mean: Mean Difference: Pooled MIJ821 0.32 mg/kg minus placebo. The MIJ821 treatment arms vs placebo are primary.p-value: 0.019680% CI: [-9.22, -2.2]ANCOVA
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.
Time frame: Baseline, 24 hours, 48 hours and 6 weeks (Day 43)
Population: Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Bech-Rafaelsen Melancholia Scale | Change at 48 hrs (n=9,10,9,7,4,19) | -9.9 Scores on a Scale | Standard Deviation 5.326 |
| Pooled MIJ821 0.16 mg/kg | Bech-Rafaelsen Melancholia Scale | Change at 24 hrs (n=11,10,10,8,9,20) | -11.9 Scores on a Scale | Standard Deviation 5.941 |
| Pooled MIJ821 0.16 mg/kg | Bech-Rafaelsen Melancholia Scale | Change at day 43 (n=8,8,8,6,9,17) | -8.6 Scores on a Scale | Standard Deviation 6.589 |
| Pooled MIJ821 0.32 mg/kg | Bech-Rafaelsen Melancholia Scale | Change at 48 hrs (n=9,10,9,7,4,19) | -8.0 Scores on a Scale | Standard Deviation 5.185 |
| Pooled MIJ821 0.32 mg/kg | Bech-Rafaelsen Melancholia Scale | Change at 24 hrs (n=11,10,10,8,9,20) | -9.5 Scores on a Scale | Standard Deviation 4.625 |
| Pooled MIJ821 0.32 mg/kg | Bech-Rafaelsen Melancholia Scale | Change at day 43 (n=8,8,8,6,9,17) | -8.6 Scores on a Scale | Standard Deviation 5.423 |
| Ketamine 0.5 mg/kg Weekly | Bech-Rafaelsen Melancholia Scale | Change at day 43 (n=8,8,8,6,9,17) | -7.6 Scores on a Scale | Standard Deviation 10.013 |
| Ketamine 0.5 mg/kg Weekly | Bech-Rafaelsen Melancholia Scale | Change at 24 hrs (n=11,10,10,8,9,20) | -7.9 Scores on a Scale | Standard Deviation 6.903 |
| Ketamine 0.5 mg/kg Weekly | Bech-Rafaelsen Melancholia Scale | Change at 48 hrs (n=9,10,9,7,4,19) | -7.6 Scores on a Scale | Standard Deviation 8.383 |
| Placebo Weekly | Bech-Rafaelsen Melancholia Scale | Change at 24 hrs (n=11,10,10,8,9,20) | -8.1 Scores on a Scale | Standard Deviation 4.612 |
| Placebo Weekly | Bech-Rafaelsen Melancholia Scale | Change at 48 hrs (n=9,10,9,7,4,19) | -8.0 Scores on a Scale | Standard Deviation 5.508 |
| Placebo Weekly | Bech-Rafaelsen Melancholia Scale | Change at day 43 (n=8,8,8,6,9,17) | -6.0 Scores on a Scale | Standard Deviation 9.338 |
| Ketamine 0.5 mg/kg Weekly | Bech-Rafaelsen Melancholia Scale | Change at 24 hrs (n=11,10,10,8,9,20) | -7.7 Scores on a Scale | Standard Deviation 5.766 |
| Ketamine 0.5 mg/kg Weekly | Bech-Rafaelsen Melancholia Scale | Change at 48 hrs (n=9,10,9,7,4,19) | -12.5 Scores on a Scale | Standard Deviation 7.853 |
| Ketamine 0.5 mg/kg Weekly | Bech-Rafaelsen Melancholia Scale | Change at day 43 (n=8,8,8,6,9,17) | -8.9 Scores on a Scale | Standard Deviation 8.343 |
| Placebo Weekly | Bech-Rafaelsen Melancholia Scale | Change at 24 hrs (n=11,10,10,8,9,20) | -6.0 Scores on a Scale | Standard Deviation 5.262 |
| Placebo Weekly | Bech-Rafaelsen Melancholia Scale | Change at day 43 (n=8,8,8,6,9,17) | -6.9 Scores on a Scale | Standard Deviation 5.988 |
| Placebo Weekly | Bech-Rafaelsen Melancholia Scale | Change at 48 hrs (n=9,10,9,7,4,19) | -6.7 Scores on a Scale | Standard Deviation 6.659 |
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.
Time frame: Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
Population: Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=2,3,3,2,4,9) | -5.77 Scores on a Scale | Standard Error 3.9 |
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at day 43 (n=3,2,3,2,8,8) | -5.79 Scores on a Scale | Standard Error 3.4 |
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=4,3,4,3,9,8) | -4.76 Scores on a Scale | Standard Error 2.9 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=4,3,4,3,9,8) | -3.64 Scores on a Scale | Standard Error 3.6 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=2,3,3,2,4,9) | -2.82 Scores on a Scale | Standard Error 3.7 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at day 43 (n=3,2,3,2,8,8) | -4.82 Scores on a Scale | Standard Error 4.4 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=2,3,3,2,4,9) | -5.92 Scores on a Scale | Standard Error 3.2 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=4,3,4,3,9,8) | -3.93 Scores on a Scale | Standard Error 3 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at day 43 (n=3,2,3,2,8,8) | -7.24 Scores on a Scale | Standard Error 3.5 |
| Placebo Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=2,3,3,2,4,9) | 1.62 Scores on a Scale | Standard Error 4 |
| Placebo Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=4,3,4,3,9,8) | 1.38 Scores on a Scale | Standard Error 3.5 |
| Placebo Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at day 43 (n=3,2,3,2,8,8) | -6.49 Scores on a Scale | Standard Error 4.3 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=2,3,3,2,4,9) | -6.68 Scores on a Scale | Standard Error 2.6 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=4,3,4,3,9,8) | -5.07 Scores on a Scale | Standard Error 2 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at day 43 (n=3,2,3,2,8,8) | -9.01 Scores on a Scale | Standard Error 2.1 |
| Placebo Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=4,3,4,3,9,8) | -3.61 Scores on a Scale | Standard Error 2 |
| Placebo Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at day 43 (n=3,2,3,2,8,8) | -5.21 Scores on a Scale | Standard Error 2.1 |
| Placebo Weekly | Change From Baseline in the CORE Melancholia Total Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=2,3,3,2,4,9) | -5.06 Scores on a Scale | Standard Error 1.9 |
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.
Time frame: Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
Population: Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | 1.80 Scores on a Scale | Standard Error 1.1 |
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | 1.38 Scores on a Scale | Standard Error 1.1 |
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | 1.82 Scores on a Scale | Standard Error 1 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | 2.30 Scores on a Scale | Standard Error 1.1 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | 1.61 Scores on a Scale | Standard Error 1.1 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | 2.00 Scores on a Scale | Standard Error 1.1 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | 1.02 Scores on a Scale | Standard Error 1.1 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | 1.20 Scores on a Scale | Standard Error 1.1 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | 1.89 Scores on a Scale | Standard Error 1.1 |
| Placebo Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | 7.22 Scores on a Scale | Standard Error 1.1 |
| Placebo Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | 3.46 Scores on a Scale | Standard Error 1.2 |
| Placebo Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | 0.24 Scores on a Scale | Standard Error 1.3 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | 1.86 Scores on a Scale | Standard Error 1.1 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | 2.10 Scores on a Scale | Standard Error 1.1 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | 1.89 Scores on a Scale | Standard Error 1.4 |
| Placebo Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | 2.43 Scores on a Scale | Standard Error 0.8 |
| Placebo Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | 2.50 Scores on a Scale | Standard Error 0.8 |
| Placebo Weekly | Change From Baseline in the Dissociative Experiences Total Score | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | 2.63 Scores on a Scale | Standard Error 0.8 |
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).
Time frame: Baseline, and at 6 weeks (day 43)
Population: Intent-to-treat analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Total Hamilton Anxiety Scale | -1.94 Scores on a Scale | Standard Error 2 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Total Hamilton Anxiety Scale | -5.69 Scores on a Scale | Standard Error 2 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Hamilton Anxiety Scale | -7.17 Scores on a Scale | Standard Error 2 |
| Placebo Weekly | Change From Baseline in the Total Hamilton Anxiety Scale | -3.83 Scores on a Scale | Standard Error 2.2 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Hamilton Anxiety Scale | -4.93 Scores on a Scale | Standard Error 2 |
| Placebo Weekly | Change From Baseline in the Total Hamilton Anxiety Scale | -4.80 Scores on a Scale | Standard Error 1.4 |
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).
Time frame: Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
Population: Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | -2.95 Scores on a Scale | Standard Error 1 |
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -2.79 Scores on a Scale | Standard Error 0.9 |
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -1.18 Scores on a Scale | Standard Error 1 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | -1.03 Scores on a Scale | Standard Error 0.9 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -2.38 Scores on a Scale | Standard Error 0.9 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -1.06 Scores on a Scale | Standard Error 1 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | -1.97 Scores on a Scale | Standard Error 1 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -1.50 Scores on a Scale | Standard Error 1 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -1.55 Scores on a Scale | Standard Error 1.1 |
| Placebo Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | -3.43 Scores on a Scale | Standard Error 1.1 |
| Placebo Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -2.46 Scores on a Scale | Standard Error 1 |
| Placebo Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -2.04 Scores on a Scale | Standard Error 1.2 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | 0.01 Scores on a Scale | Standard Error 1.3 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -1.28 Scores on a Scale | Standard Error 1 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -1.68 Scores on a Scale | Standard Error 1 |
| Placebo Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -2.33 Scores on a Scale | Standard Error 0.7 |
| Placebo Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -1.59 Scores on a Scale | Standard Error 0.7 |
| Placebo Weekly | Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale | Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19) | -1.97 Scores on a Scale | Standard Error 0.7 |
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.
Time frame: Baseline, and at 48 hours
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs | -14.94 Scores on a Scale | Standard Error 2.2 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs | -15.25 Scores on a Scale | Standard Error 2.4 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs | -18.89 Scores on a Scale | Standard Error 4.8 |
| Placebo Weekly | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs | -7.88 Scores on a Scale | Standard Error 2.2 |
Comparison: Comparison of adjusted arithmetic mean: Mean Difference: Pooled MIJ821 0.16 mg/kg minus placebo.p-value: 0.01380% CI: [-11.06, -3.06]ANCOVA
Comparison: Comparison of adjusted arithmetic mean: Mean Difference: Pooled MIJ821 0.32 mg/kg minus placebo.p-value: 0.013380% CI: [-11.57, -3.18]ANCOVA
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.
Time frame: Baseline, and at Week 6
Population: Intent to Treat analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6 | -12.71 Scores on a Scale | Standard Error 3.4 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6 | -14.08 Scores on a Scale | Standard Error 3.4 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6 | -13.04 Scores on a Scale | Standard Error 3.5 |
| Placebo Weekly | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6 | -10.68 Scores on a Scale | Standard Error 3.9 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6 | -12.86 Scores on a Scale | Standard Error 3.3 |
| Placebo Weekly | Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6 | -7.62 Scores on a Scale | Standard Error 2.3 |
Comparison: Comparison of adjusted arithmetic mean: Mean Difference: MIJ821 0.16 mg/kg weekly minus placebo.p-value: 0.108280% CI: [-10.37, 0.19]ANCOVA
Comparison: Comparison of adjusted arithmetic mean: Mean Difference: MIJ821 0.32 mg/kg weekly minus placebo.p-value: 0.099380% CI: [-10.83, -0.02]ANCOVA
Comparison: Comparison of adjusted arithmetic mean: Mean Difference: MIJ821 0.16 mg/kg biweekly minus placebo.p-value: 0.059880% CI: [-11.78, -1.15]ANCOVA
Comparison: Comparison of adjusted arithmetic mean: Mean Difference: MIJ821 0.32 mg/kg biweekly minus placebo.p-value: 0.249180% CI: [-8.86, 2.74]ANCOVA
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.
Time frame: Baseline, 24 hours, and 6 weeks (day 43)
Population: Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -1.28 Scores on a Scale | Standard Error 0.6 |
| Pooled MIJ821 0.16 mg/kg | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -1.41 Scores on a Scale | Standard Error 0.5 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -2.13 Scores on a Scale | Standard Error 0.7 |
| Pooled MIJ821 0.32 mg/kg | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -1.07 Scores on a Scale | Standard Error 0.5 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -0.65 Scores on a Scale | Standard Error 0.7 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -1.66 Scores on a Scale | Standard Error 0.5 |
| Placebo Weekly | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -0.81 Scores on a Scale | Standard Error 0.5 |
| Placebo Weekly | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -1.55 Scores on a Scale | Standard Error 0.7 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -1.56 Scores on a Scale | Standard Error 0.5 |
| Ketamine 0.5 mg/kg Weekly | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -1.80 Scores on a Scale | Standard Error 0.7 |
| Placebo Weekly | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20) | -0.72 Scores on a Scale | Standard Error 0.3 |
| Placebo Weekly | Change From Baseline in the Young Mania Rating Scale | Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17) | -0.92 Scores on a Scale | Standard Error 0.4 |
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.
Time frame: Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
Population: Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Clinician-Administered Dissociative States Scale | Change at 48 hrs (n=9,10,9,7,4,19) | -0.22 Scores on a Scale | Standard Deviation 0.667 |
| Pooled MIJ821 0.16 mg/kg | Clinician-Administered Dissociative States Scale | Change at 24 hrs (n=11,10,10,8,10,20) | 1.09 Scores on a Scale | Standard Deviation 5.262 |
| Pooled MIJ821 0.16 mg/kg | Clinician-Administered Dissociative States Scale | Change at day 43 (n=8,8,8,6,9,17) | 0.00 Scores on a Scale | Standard Deviation 1.927 |
| Pooled MIJ821 0.32 mg/kg | Clinician-Administered Dissociative States Scale | Change at 48 hrs (n=9,10,9,7,4,19) | 0.50 Scores on a Scale | Standard Deviation 2.369 |
| Pooled MIJ821 0.32 mg/kg | Clinician-Administered Dissociative States Scale | Change at 24 hrs (n=11,10,10,8,10,20) | 1.10 Scores on a Scale | Standard Deviation 2.726 |
| Pooled MIJ821 0.32 mg/kg | Clinician-Administered Dissociative States Scale | Change at day 43 (n=8,8,8,6,9,17) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Ketamine 0.5 mg/kg Weekly | Clinician-Administered Dissociative States Scale | Change at 48 hrs (n=9,10,9,7,4,19) | 4.44 Scores on a Scale | Standard Deviation 10.394 |
| Ketamine 0.5 mg/kg Weekly | Clinician-Administered Dissociative States Scale | Change at 24 hrs (n=11,10,10,8,10,20) | 2.10 Scores on a Scale | Standard Deviation 3.414 |
| Ketamine 0.5 mg/kg Weekly | Clinician-Administered Dissociative States Scale | Change at day 43 (n=8,8,8,6,9,17) | 0.38 Scores on a Scale | Standard Deviation 1.061 |
| Placebo Weekly | Clinician-Administered Dissociative States Scale | Change at 48 hrs (n=9,10,9,7,4,19) | 3.14 Scores on a Scale | Standard Deviation 3.976 |
| Placebo Weekly | Clinician-Administered Dissociative States Scale | Change at 24 hrs (n=11,10,10,8,10,20) | 3.00 Scores on a Scale | Standard Deviation 3.703 |
| Placebo Weekly | Clinician-Administered Dissociative States Scale | Change at day 43 (n=8,8,8,6,9,17) | 1.00 Scores on a Scale | Standard Deviation 2.449 |
| Ketamine 0.5 mg/kg Weekly | Clinician-Administered Dissociative States Scale | Change at 48 hrs (n=9,10,9,7,4,19) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Ketamine 0.5 mg/kg Weekly | Clinician-Administered Dissociative States Scale | Change at 24 hrs (n=11,10,10,8,10,20) | -0.50 Scores on a Scale | Standard Deviation 0.707 |
| Ketamine 0.5 mg/kg Weekly | Clinician-Administered Dissociative States Scale | Change at day 43 (n=8,8,8,6,9,17) | 0.00 Scores on a Scale | Standard Deviation 1.118 |
| Placebo Weekly | Clinician-Administered Dissociative States Scale | Change at 24 hrs (n=11,10,10,8,10,20) | -0.25 Scores on a Scale | Standard Deviation 0.716 |
| Placebo Weekly | Clinician-Administered Dissociative States Scale | Change at day 43 (n=8,8,8,6,9,17) | -0.18 Scores on a Scale | Standard Deviation 0.636 |
| Placebo Weekly | Clinician-Administered Dissociative States Scale | Change at 48 hrs (n=9,10,9,7,4,19) | -0.16 Scores on a Scale | Standard Deviation 0.375 |
Secondary
Percentage of Participants With Treatment Remissions (MADRS<7)
Percentage of Participants with treatment remissions as assessed via (MADRS\<7)
Time frame: 24 hours, 48 hours, and 6 weeks (Day 43)
Population: Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 48 hrs (n=9,10,9,7,4,19) | 22.2 Percentage of Participants |
| Pooled MIJ821 0.16 mg/kg | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at Day 43 (n=8,8,8,6, 9,17) | 25.0 Percentage of Participants |
| Pooled MIJ821 0.16 mg/kg | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 24 hrs (n=11,10,10,8,10,20) | 9.1 Percentage of Participants |
| Pooled MIJ821 0.32 mg/kg | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 48 hrs (n=9,10,9,7,4,19) | 10.0 Percentage of Participants |
| Pooled MIJ821 0.32 mg/kg | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at Day 43 (n=8,8,8,6, 9,17) | 37.5 Percentage of Participants |
| Pooled MIJ821 0.32 mg/kg | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 24 hrs (n=11,10,10,8,10,20) | 20.0 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at Day 43 (n=8,8,8,6, 9,17) | 0 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 24 hrs (n=11,10,10,8,10,20) | 0 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 48 hrs (n=9,10,9,7,4,19) | 11.1 Percentage of Participants |
| Placebo Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 24 hrs (n=11,10,10,8,10,20) | 11.1 Percentage of Participants |
| Placebo Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 48 hrs (n=9,10,9,7,4,19) | 28.6 Percentage of Participants |
| Placebo Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at Day 43 (n=8,8,8,6, 9,17) | 16.7 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at Day 43 (n=8,8,8,6, 9,17) | 22.2 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 24 hrs (n=11,10,10,8,10,20) | 20.0 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 48 hrs (n=9,10,9,7,4,19) | 25.0 Percentage of Participants |
| Placebo Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 48 hrs (n=9,10,9,7,4,19) | 10.5 Percentage of Participants |
| Placebo Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at 24 hrs (n=11,10,10,8,10,20) | 5.0 Percentage of Participants |
| Placebo Weekly | Percentage of Participants With Treatment Remissions (MADRS<7) | % of participants with remission at Day 43 (n=8,8,8,6, 9,17) | 11.8 Percentage of Participants |
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.
Time frame: Day 1
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL) | 462 h*ng/mL | Standard Deviation 232 |
| Pooled MIJ821 0.32 mg/kg | PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL) | 713 h*ng/mL | Standard Deviation 275 |
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.
Time frame: Day 1
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL) | 496 h*ng/mL | Standard Deviation 239 |
| Pooled MIJ821 0.32 mg/kg | PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL) | 738 h*ng/mL | Standard Deviation 302 |
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.
Time frame: Day 1
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | PK Properties of MIJ821 in Plasma - Cmax (ng/mL) | 99.5 ng/mL | Standard Deviation 47.8 |
| Pooled MIJ821 0.32 mg/kg | PK Properties of MIJ821 in Plasma - Cmax (ng/mL) | 149 ng/mL | Standard Deviation 63.4 |
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.
Time frame: Day 1
Population: PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pooled MIJ821 0.16 mg/kg | PK Properties of MIJ821 in Plasma - Tmax (ng/mL) | 0.683 hour |
| Pooled MIJ821 0.32 mg/kg | PK Properties of MIJ821 in Plasma - Tmax (ng/mL) | 0.667 hour |
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.
Time frame: 24 hours, 48 hours, and 6 weeks (Day 43)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 24 hrs - drugs (n=5,5,5) | 40.0 Percentage of Participants |
| Pooled MIJ821 0.16 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 24 hrs - placebo (n=1,1,1) | 0 Percentage of Participants |
| Pooled MIJ821 0.16 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 48 hrs - drugs (N=6, 6, 6) | 50.0 Percentage of Participants |
| Pooled MIJ821 0.16 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 48 hrs - placebo (n=2,2,2) | 0 Percentage of Participants |
| Pooled MIJ821 0.16 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at Day 43 - drugs (n=9,9,9) | 55.6 Percentage of Participants |
| Pooled MIJ821 0.16 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at Day 43- placebo (n=3,3,3) | 33.3 Percentage of Participants |
| Pooled MIJ821 0.32 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at Day 43- placebo (n=3,3,3) | 0 Percentage of Participants |
| Pooled MIJ821 0.32 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 24 hrs - drugs (n=5,5,5) | 0 Percentage of Participants |
| Pooled MIJ821 0.32 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 48 hrs - placebo (n=2,2,2) | 0 Percentage of Participants |
| Pooled MIJ821 0.32 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at Day 43 - drugs (n=9,9,9) | 0 Percentage of Participants |
| Pooled MIJ821 0.32 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 24 hrs - placebo (n=1,1,1) | 0 Percentage of Participants |
| Pooled MIJ821 0.32 mg/kg | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 48 hrs - drugs (N=6, 6, 6) | 0 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 24 hrs - placebo (n=1,1,1) | 100 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 48 hrs - drugs (N=6, 6, 6) | 33.3 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at Day 43- placebo (n=3,3,3) | 0 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 48 hrs - placebo (n=2,2,2) | 50.0 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at 24 hrs - drugs (n=5,5,5) | 20.0 Percentage of Participants |
| Ketamine 0.5 mg/kg Weekly | Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor. | % of participants who responded at Day 43 - drugs (n=9,9,9) | 44.4 Percentage of Participants |
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.
Time frame: Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
Population: Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score Change at 48 hrs (n=9,10,9,7,4,19) | -0.22 Scores on a Scale | Standard Deviation 0.667 |
| Pooled MIJ821 0.16 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at Day 43 (n=8,8,8,6,9,17) | -0.38 Scores on a Scale | Standard Deviation 0.744 |
| Pooled MIJ821 0.16 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at day 43 (n=8,8,8,6,9,17) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Pooled MIJ821 0.16 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at day 43 (n=8,8,8,6,9,17) | -0.38 Scores on a Scale | Standard Deviation 0.744 |
| Pooled MIJ821 0.16 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.45 Scores on a Scale | Standard Deviation 0.82 |
| Pooled MIJ821 0.16 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | -0.22 Scores on a Scale | Standard Deviation 0.667 |
| Pooled MIJ821 0.16 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Pooled MIJ821 0.16 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Pooled MIJ821 0.16 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.45 Scores on a Scale | Standard Deviation 0.82 |
| Pooled MIJ821 0.32 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at Day 43 (n=8,8,8,6,9,17) | -0.13 Scores on a Scale | Standard Deviation 0.354 |
| Pooled MIJ821 0.32 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at day 43 (n=8,8,8,6,9,17) | -0.13 Scores on a Scale | Standard Deviation 0.354 |
| Pooled MIJ821 0.32 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Pooled MIJ821 0.32 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at day 43 (n=8,8,8,6,9,17) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Pooled MIJ821 0.32 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Pooled MIJ821 0.32 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score Change at 48 hrs (n=9,10,9,7,4,19) | -0.50 Scores on a Scale | Standard Deviation 0.85 |
| Pooled MIJ821 0.32 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.50 Scores on a Scale | Standard Deviation 0.85 |
| Pooled MIJ821 0.32 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.50 Scores on a Scale | Standard Deviation 0.85 |
| Pooled MIJ821 0.32 mg/kg | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | -0.50 Scores on a Scale | Standard Deviation 0.85 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at day 43 (n=8,8,8,6,9,17) | -0.13 Scores on a Scale | Standard Deviation 1.126 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.30 Scores on a Scale | Standard Deviation 0.675 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score Change at 48 hrs (n=9,10,9,7,4,19) | -0.33 Scores on a Scale | Standard Deviation 0.707 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at Day 43 (n=8,8,8,6,9,17) | -0.13 Scores on a Scale | Standard Deviation 1.126 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at day 43 (n=8,8,8,6,9,17) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.30 Scores on a Scale | Standard Deviation 0.675 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | -0.33 Scores on a Scale | Standard Deviation 0.707 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at day 43 (n=8,8,8,6,9,17) | 0.00 Scores on a Scale | Standard Deviation 1.265 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | 0.11 Scores on a Scale | Standard Deviation 0.333 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at day 43 (n=8,8,8,6,9,17) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | 0.11 Scores on a Scale | Standard Deviation 1.269 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | -0.43 Scores on a Scale | Standard Deviation 0.787 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at 24 hrs (n=11,10,10,9,10,20) | 0.11 Scores on a Scale | Standard Deviation 1.764 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score Change at 48 hrs (n=9,10,9,7,4,19) | -0.57 Scores on a Scale | Standard Deviation 1.134 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at Day 43 (n=8,8,8,6,9,17) | -0.17 Scores on a Scale | Standard Deviation 1.602 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.40 Scores on a Scale | Standard Deviation 0.966 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.50 Scores on a Scale | Standard Deviation 1.269 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at day 43 (n=8,8,8,6,9,17) | -0.11 Scores on a Scale | Standard Deviation 0.333 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at Day 43 (n=8,8,8,6,9,17) | -0.22 Scores on a Scale | Standard Deviation 1.563 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score Change at 48 hrs (n=9,10,9,7,4,19) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.10 Scores on a Scale | Standard Deviation 0.316 |
| Ketamine 0.5 mg/kg Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at day 43 (n=8,8,8,6,9,17) | -0.11 Scores on a Scale | Standard Deviation 1.269 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | 0.00 Scores on a Scale | Standard Deviation 0 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.20 Scores on a Scale | Standard Deviation 0.523 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at day 43 (n=8,8,8,6,9,17) | 0.12 Scores on a Scale | Standard Deviation 1.111 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at Day 43 (n=8,8,8,6,9,17) | 0.47 Scores on a Scale | Standard Deviation 2.503 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score Change at 48 hrs (n=9,10,9,7,4,19) | -0.16 Scores on a Scale | Standard Deviation 0.375 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | SSTS total score - Change at 24 hrs (n=11,10,10,9,10,20) | -0.20 Scores on a Scale | Standard Deviation 0.523 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at day 43 (n=8,8,8,6,9,17) | 0.12 Scores on a Scale | Standard Deviation 0.485 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal ideation subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | -0.16 Scores on a Scale | Standard Deviation 0.375 |
| Placebo Weekly | Sheehan Suicidality Tracking Scale - (SSTS) | Suicidal behavior subscale score - Change at 48 hrs (n=9,10,9,7,4,19) | 0.00 Scores on a Scale | Standard Deviation 0 |
Secondary
Summary of Adverse Events
Summary of Adverse Events
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.
Population: safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Summary of Adverse Events | Study drug-related AEs leading to discontinuation of study treatment | 0 Participants |
| Pooled MIJ821 0.16 mg/kg | Summary of Adverse Events | AEs leading to discontinuation of study treatment | 1 Participants |
| Pooled MIJ821 0.16 mg/kg | Summary of Adverse Events | AEs, subjects with AEs | 7 Participants |
| Pooled MIJ821 0.16 mg/kg | Summary of Adverse Events | Study drug-related AEs | 5 Participants |
| Pooled MIJ821 0.16 mg/kg | Summary of Adverse Events | SAEs | 0 Participants |
| Pooled MIJ821 0.32 mg/kg | Summary of Adverse Events | AEs leading to discontinuation of study treatment | 0 Participants |
| Pooled MIJ821 0.32 mg/kg | Summary of Adverse Events | SAEs | 1 Participants |
| Pooled MIJ821 0.32 mg/kg | Summary of Adverse Events | Study drug-related AEs leading to discontinuation of study treatment | 0 Participants |
| Pooled MIJ821 0.32 mg/kg | Summary of Adverse Events | AEs, subjects with AEs | 6 Participants |
| Pooled MIJ821 0.32 mg/kg | Summary of Adverse Events | Study drug-related AEs | 5 Participants |
| Ketamine 0.5 mg/kg Weekly | Summary of Adverse Events | Study drug-related AEs | 7 Participants |
| Ketamine 0.5 mg/kg Weekly | Summary of Adverse Events | AEs, subjects with AEs | 7 Participants |
| Ketamine 0.5 mg/kg Weekly | Summary of Adverse Events | SAEs | 0 Participants |
| Ketamine 0.5 mg/kg Weekly | Summary of Adverse Events | AEs leading to discontinuation of study treatment | 0 Participants |
| Ketamine 0.5 mg/kg Weekly | Summary of Adverse Events | Study drug-related AEs leading to discontinuation of study treatment | 0 Participants |
| Placebo Weekly | Summary of Adverse Events | SAEs | 3 Participants |
| Placebo Weekly | Summary of Adverse Events | Study drug-related AEs | 5 Participants |
| Placebo Weekly | Summary of Adverse Events | AEs leading to discontinuation of study treatment | 2 Participants |
| Placebo Weekly | Summary of Adverse Events | Study drug-related AEs leading to discontinuation of study treatment | 0 Participants |
| Placebo Weekly | Summary of Adverse Events | AEs, subjects with AEs | 6 Participants |
| Ketamine 0.5 mg/kg Weekly | Summary of Adverse Events | Study drug-related AEs leading to discontinuation of study treatment | 0 Participants |
| Ketamine 0.5 mg/kg Weekly | Summary of Adverse Events | SAEs | 0 Participants |
| Ketamine 0.5 mg/kg Weekly | Summary of Adverse Events | Study drug-related AEs | 6 Participants |
| Ketamine 0.5 mg/kg Weekly | Summary of Adverse Events | AEs leading to discontinuation of study treatment | 0 Participants |
| Ketamine 0.5 mg/kg Weekly | Summary of Adverse Events | AEs, subjects with AEs | 6 Participants |
| Placebo Weekly | Summary of Adverse Events | AEs leading to discontinuation of study treatment | 1 Participants |
| Placebo Weekly | Summary of Adverse Events | Study drug-related AEs leading to discontinuation of study treatment | 1 Participants |
| Placebo Weekly | Summary of Adverse Events | AEs, subjects with AEs | 7 Participants |
| Placebo Weekly | Summary of Adverse Events | Study drug-related AEs | 5 Participants |
| Placebo Weekly | Summary of Adverse Events | SAEs | 1 Participants |
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).
Time frame: Change from baseline at week 6 (Day 43)
Population: Intent-to-treat analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled MIJ821 0.16 mg/kg | Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline | -2.6 Scores on a Scale | Standard Deviation 6.927 |
| Pooled MIJ821 0.32 mg/kg | Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline | -5.4 Scores on a Scale | Standard Deviation 4.565 |
| Ketamine 0.5 mg/kg Weekly | Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline | -6.8 Scores on a Scale | Standard Deviation 6.606 |
| Placebo Weekly | Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline | -4.2 Scores on a Scale | Standard Deviation 9.432 |
| Ketamine 0.5 mg/kg Weekly | Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline | -5.4 Scores on a Scale | Standard Deviation 7.763 |
| Placebo Weekly | Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline | -5.1 Scores on a Scale | Standard Deviation 5.651 |