Trial Outcomes & Findings for Proof of Concept Study Evaluating the Efficacy and Safety of MIJ821 in Patients With Treatment-resistant Depression (NCT NCT03756129)

Last Updated: 2021-10-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

70 participants

Primary outcome timeframe

Baseline, and at 24 hours

Results posted on

2021-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	MIJ821 0.16 mg/kg Weekly MIJ821 0.16 mg/kg weekly	MIJ821 0.16 mg/kg Biweekly MIJ821 0.16 mg/kg biweekly	MIJ821 0.32 mg/kg Weekly MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly Ketamine 0.5 mg/kg weekly	Placebo Weekly Placebo weekly
Overall Study STARTED	11	10	10	9	10	20
Overall Study COMPLETED	8	8	7	6	9	15
Overall Study NOT COMPLETED	3	2	3	3	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	MIJ821 0.16 mg/kg Weekly MIJ821 0.16 mg/kg weekly	MIJ821 0.16 mg/kg Biweekly MIJ821 0.16 mg/kg biweekly	MIJ821 0.32 mg/kg Weekly MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly Ketamine 0.5 mg/kg weekly	Placebo Weekly Placebo weekly
Overall Study Adverse Event	1	1	0	2	0	0
Overall Study Withdrawal by Subject	2	1	3	1	1	3
Overall Study Lost to Follow-up	0	0	0	0	0	1
Overall Study Physician Decision	0	0	0	0	0	1

Baseline Characteristics

Proof of Concept Study Evaluating the Efficacy and Safety of MIJ821 in Patients With Treatment-resistant Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MIJ821 0.16 mg/kg Weekly n=11 Participants MIJ821 0.16 mg/kg weekly	MIJ821 0.16 mg/kg Biweekly n=10 Participants MIJ821 0.16 mg/kg biweekly	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=9 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=10 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 Participants Placebo weekly	Total n=70 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=99 Participants	9 Participants n=107 Participants	10 Participants n=206 Participants	9 Participants n=7 Participants	10 Participants n=31 Participants	20 Participants n=30 Participants	69 Participants n=3 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants
Age, Continuous	48.6 Years STANDARD_DEVIATION 11.70 • n=99 Participants	53.7 Years STANDARD_DEVIATION 9.33 • n=107 Participants	42.9 Years STANDARD_DEVIATION 14.47 • n=206 Participants	46.6 Years STANDARD_DEVIATION 11.83 • n=7 Participants	52.3 Years STANDARD_DEVIATION 6.96 • n=31 Participants	44.8 Years STANDARD_DEVIATION 10.69 • n=30 Participants	47.7 Years STANDARD_DEVIATION 11.27 • n=3 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	5 Participants n=107 Participants	6 Participants n=206 Participants	6 Participants n=7 Participants	7 Participants n=31 Participants	9 Participants n=30 Participants	35 Participants n=3 Participants
Sex: Female, Male Male	9 Participants n=99 Participants	5 Participants n=107 Participants	4 Participants n=206 Participants	3 Participants n=7 Participants	3 Participants n=31 Participants	11 Participants n=30 Participants	35 Participants n=3 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	1 Participants n=30 Participants	1 Participants n=3 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants
Race (NIH/OMB) Black or African American	3 Participants n=99 Participants	4 Participants n=107 Participants	4 Participants n=206 Participants	8 Participants n=7 Participants	0 Participants n=31 Participants	10 Participants n=30 Participants	29 Participants n=3 Participants
Race (NIH/OMB) White	8 Participants n=99 Participants	6 Participants n=107 Participants	6 Participants n=206 Participants	1 Participants n=7 Participants	9 Participants n=31 Participants	9 Participants n=30 Participants	39 Participants n=3 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants

PRIMARY outcome

Timeframe: Baseline, and at 24 hours

Population: Intent to Treat analysis set

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=20 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly Ketamine 0.5 mg/kg weekly	Placebo Weekly Placebo weekly	Pooled MIJ821 0.16 mg/kg n=21 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=19 Participants Pooled MIJ821 0.32 mg/kg
Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs	-12.94 Scores on a Scale Standard Error 2.7	-7.27 Scores on a Scale Standard Error 1.9	—	—	-15.51 Scores on a Scale Standard Error 1.9	-12.98 Scores on a Scale Standard Error 1.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=4 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=19 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly Ketamine 0.5 mg/kg weekly	Placebo Weekly Placebo weekly	Pooled MIJ821 0.16 mg/kg n=19 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=16 Participants Pooled MIJ821 0.32 mg/kg
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	-7.88 Scores on a Scale Standard Error 2.2	—	—	-14.94 Scores on a Scale Standard Error 2.2	-15.25 Scores on a Scale Standard Error 2.4

SECONDARY outcome

Timeframe: Baseline, and at Week 6

Population: Intent to Treat analysis set

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=8 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=6 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=9 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=17 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=8 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=8 Participants Pooled MIJ821 0.32 mg/kg
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	-10.68 Scores on a Scale Standard Error 3.9	-12.86 Scores on a Scale Standard Error 3.3	-7.62 Scores on a Scale Standard Error 2.3	-12.71 Scores on a Scale Standard Error 3.4	-14.08 Scores on a Scale Standard Error 3.4

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=9 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=10 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=11 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=10 Participants 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)	-1.66 Scores on a Scale Standard Error 0.5	-0.81 Scores on a Scale Standard Error 0.5	-1.56 Scores on a Scale Standard Error 0.5	-0.72 Scores on a Scale Standard Error 0.3	-1.41 Scores on a Scale Standard Error 0.5	-1.07 Scores on a Scale Standard Error 0.5
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	-1.55 Scores on a Scale Standard Error 0.7	-1.80 Scores on a Scale Standard Error 0.7	-0.92 Scores on a Scale Standard Error 0.4	-1.28 Scores on a Scale Standard Error 0.6	-2.13 Scores on a Scale Standard Error 0.7

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=9 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=10 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=11 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=10 Participants Pooled MIJ821 0.32 mg/kg
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	-8.1 Scores on a Scale Standard Deviation 4.612	-7.7 Scores on a Scale Standard Deviation 5.766	-6.0 Scores on a Scale Standard Deviation 5.262	-11.9 Scores on a Scale Standard Deviation 5.941	-9.5 Scores on a Scale Standard Deviation 4.625
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	-8.0 Scores on a Scale Standard Deviation 5.508	-12.5 Scores on a Scale Standard Deviation 7.853	-6.7 Scores on a Scale Standard Deviation 6.659	-9.9 Scores on a Scale Standard Deviation 5.326	-8.0 Scores on a Scale Standard Deviation 5.185
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	-6.0 Scores on a Scale Standard Deviation 9.338	-8.9 Scores on a Scale Standard Deviation 8.343	-6.9 Scores on a Scale Standard Deviation 5.988	-8.6 Scores on a Scale Standard Deviation 6.589	-8.6 Scores on a Scale Standard Deviation 5.423

SECONDARY outcome

Timeframe: Day 1

Population: PK analysis set

To assess MIJ821 pharmacokinetics in plasma described by Cmax. A single, sparse PK measurement was taken on Day 1.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly Ketamine 0.5 mg/kg weekly	Placebo Weekly Placebo weekly	Pooled MIJ821 0.16 mg/kg n=14 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=11 Participants Pooled MIJ821 0.32 mg/kg
PK Properties of MIJ821 in Plasma - Cmax (ng/mL)	—	—	—	—	99.5 ng/mL Standard Deviation 47.8	149 ng/mL Standard Deviation 63.4

SECONDARY outcome

Timeframe: Day 1

Population: PK analysis set

To assess MIJ821 pharmacokinetics in plasma described by Tmax. A single, sparse PK measurement was taken on Day 1.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly Ketamine 0.5 mg/kg weekly	Placebo Weekly Placebo weekly	Pooled MIJ821 0.16 mg/kg n=14 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=11 Participants Pooled MIJ821 0.32 mg/kg
PK Properties of MIJ821 in Plasma - Tmax (ng/mL)	—	—	—	—	0.683 hour Interval 0.65 to 0.7	0.667 hour Interval 0.667 to 0.7

SECONDARY outcome

Timeframe: Day 1

Population: PK analysis set

To assess MIJ821 pharmacokinetics in plasma described by AUClast (h\*ng/mL). A single, sparse PK measurement was taken on Day 1.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly Ketamine 0.5 mg/kg weekly	Placebo Weekly Placebo weekly	Pooled MIJ821 0.16 mg/kg n=14 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=11 Participants Pooled MIJ821 0.32 mg/kg
PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL)	—	—	—	—	496 h*ng/mL Standard Deviation 239	738 h*ng/mL Standard Deviation 302

SECONDARY outcome

Timeframe: Day 1

Population: PK analysis set

To assess MIJ821 pharmacokinetics in plasma described by AUC0-24h (h\*ng/mL). A single, sparse PK measurement was taken on Day 1.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly Ketamine 0.5 mg/kg weekly	Placebo Weekly Placebo weekly	Pooled MIJ821 0.16 mg/kg n=13 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=11 Participants Pooled MIJ821 0.32 mg/kg
PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL)	—	—	—	—	462 h*ng/mL Standard Deviation 232	713 h*ng/mL Standard Deviation 275

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=9 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=10 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=11 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=10 Participants 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)	-3.93 Scores on a Scale Standard Error 3.0	1.38 Scores on a Scale Standard Error 3.5	-5.07 Scores on a Scale Standard Error 2.0	-3.61 Scores on a Scale Standard Error 2.0	-4.76 Scores on a Scale Standard Error 2.9	-3.64 Scores on a Scale Standard Error 3.6
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	1.62 Scores on a Scale Standard Error 4.0	-6.68 Scores on a Scale Standard Error 2.6	-5.06 Scores on a Scale Standard Error 1.9	-5.77 Scores on a Scale Standard Error 3.9	-2.82 Scores on a Scale Standard Error 3.7
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	-6.49 Scores on a Scale Standard Error 4.3	-9.01 Scores on a Scale Standard Error 2.1	-5.21 Scores on a Scale Standard Error 2.1	-5.79 Scores on a Scale Standard Error 3.4	-4.82 Scores on a Scale Standard Error 4.4

SECONDARY outcome

Timeframe: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 post treatment, up to a maximum duration of 66 days.

Population: safety analysis set

Summary of Adverse Events

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=9 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=10 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=11 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=10 Participants Pooled MIJ821 0.32 mg/kg
Summary of Adverse Events AEs, subjects with AEs	7 Participants	6 Participants	6 Participants	7 Participants	7 Participants	6 Participants
Summary of Adverse Events Study drug-related AEs	7 Participants	5 Participants	6 Participants	5 Participants	5 Participants	5 Participants
Summary of Adverse Events SAEs	0 Participants	3 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Summary of Adverse Events AEs leading to discontinuation of study treatment	0 Participants	2 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Summary of Adverse Events Study drug-related AEs leading to discontinuation of study treatment	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=9 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=10 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=11 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=10 Participants Pooled MIJ821 0.32 mg/kg
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	3.00 Scores on a Scale Standard Deviation 3.703	-0.50 Scores on a Scale Standard Deviation 0.707	-0.25 Scores on a Scale Standard Deviation 0.716	1.09 Scores on a Scale Standard Deviation 5.262	1.10 Scores on a Scale Standard Deviation 2.726
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	3.14 Scores on a Scale Standard Deviation 3.976	0.00 Scores on a Scale Standard Deviation 0.00	-0.16 Scores on a Scale Standard Deviation 0.375	-0.22 Scores on a Scale Standard Deviation 0.667	0.50 Scores on a Scale Standard Deviation 2.369
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	1.00 Scores on a Scale Standard Deviation 2.449	0.00 Scores on a Scale Standard Deviation 1.118	-0.18 Scores on a Scale Standard Deviation 0.636	0.00 Scores on a Scale Standard Deviation 1.927	0.00 Scores on a Scale Standard Deviation 0.00

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=9 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=10 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=11 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=10 Participants 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)	1.20 Scores on a Scale Standard Error 1.1	7.22 Scores on a Scale Standard Error 1.1	2.10 Scores on a Scale Standard Error 1.1	2.50 Scores on a Scale Standard Error 0.8	1.82 Scores on a Scale Standard Error 1.0	2.00 Scores on a Scale Standard Error 1.1
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	3.46 Scores on a Scale Standard Error 1.2	1.89 Scores on a Scale Standard Error 1.4	2.43 Scores on a Scale Standard Error 0.8	1.80 Scores on a Scale Standard Error 1.1	2.30 Scores on a Scale Standard Error 1.1
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	0.24 Scores on a Scale Standard Error 1.3	1.86 Scores on a Scale Standard Error 1.1	2.63 Scores on a Scale Standard Error 0.8	1.38 Scores on a Scale Standard Error 1.1	1.61 Scores on a Scale Standard Error 1.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=9 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=10 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=11 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=10 Participants 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 0.00	0.11 Scores on a Scale Standard Deviation 0.333	-0.10 Scores on a Scale Standard Deviation 0.316	0.00 Scores on a Scale Standard Deviation 0.00	0.00 Scores on a Scale Standard Deviation 0.00	0.00 Scores on a Scale Standard Deviation 0.00
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 0.00	0.00 Scores on a Scale Standard Deviation 0.00	0.00 Scores on a Scale Standard Deviation 0.00	0.00 Scores on a Scale Standard Deviation 0.00	0.00 Scores on a Scale Standard Deviation 0.00	0.00 Scores on a Scale Standard Deviation 0.00
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 0.00	0.00 Scores on a Scale Standard Deviation 0.00	-0.11 Scores on a Scale Standard Deviation 0.333	0.12 Scores on a Scale Standard Deviation 0.485	0.00 Scores on a Scale Standard Deviation 0.00	0.00 Scores on a Scale Standard Deviation 0.00
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	0.11 Scores on a Scale Standard Deviation 1.269	-0.40 Scores on a Scale Standard Deviation 0.966	-0.20 Scores on a Scale Standard Deviation 0.523	-0.45 Scores on a Scale Standard Deviation 0.820	-0.50 Scores on a Scale Standard Deviation 0.850
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	-0.43 Scores on a Scale Standard Deviation 0.787	0.00 Scores on a Scale Standard Deviation 0.00	-0.16 Scores on a Scale Standard Deviation 0.375	-0.22 Scores on a Scale Standard Deviation 0.667	-0.50 Scores on a Scale Standard Deviation 0.850
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	0.00 Scores on a Scale Standard Deviation 1.265	-0.11 Scores on a Scale Standard Deviation 1.269	0.12 Scores on a Scale Standard Deviation 1.111	-0.38 Scores on a Scale Standard Deviation 0.744	-0.13 Scores on a Scale Standard Deviation 0.354
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	0.11 Scores on a Scale Standard Deviation 1.764	-0.50 Scores on a Scale Standard Deviation 1.269	-0.20 Scores on a Scale Standard Deviation 0.523	-0.45 Scores on a Scale Standard Deviation 0.820	-0.50 Scores on a Scale Standard Deviation 0.850
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	-0.57 Scores on a Scale Standard Deviation 1.134	0.00 Scores on a Scale Standard Deviation 0.00	-0.16 Scores on a Scale Standard Deviation 0.375	-0.22 Scores on a Scale Standard Deviation 0.667	-0.50 Scores on a Scale Standard Deviation 0.850
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	-0.17 Scores on a Scale Standard Deviation 1.602	-0.22 Scores on a Scale Standard Deviation 1.563	0.47 Scores on a Scale Standard Deviation 2.503	-0.38 Scores on a Scale Standard Deviation 0.744	-0.13 Scores on a Scale Standard Deviation 0.354

SECONDARY outcome

Timeframe: 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.

Percentage of Participants with treatment remissions as assessed via (MADRS\<7)

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=9 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=10 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=11 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=10 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)	0 Percentage of Participants	11.1 Percentage of Participants	20.0 Percentage of Participants	5.0 Percentage of Participants	9.1 Percentage of Participants	20.0 Percentage of Participants
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	28.6 Percentage of Participants	25.0 Percentage of Participants	10.5 Percentage of Participants	22.2 Percentage of Participants	10.0 Percentage of Participants
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	16.7 Percentage of Participants	22.2 Percentage of Participants	11.8 Percentage of Participants	25.0 Percentage of Participants	37.5 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, and at 6 weeks (day 43)

Population: Intent-to-treat analysis set

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).

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=8 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=6 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=8 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=17 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=8 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=8 Participants Pooled MIJ821 0.32 mg/kg
Change From Baseline in the Total Hamilton Anxiety Scale	-7.17 Scores on a Scale Standard Error 2.0	-3.83 Scores on a Scale Standard Error 2.2	-4.93 Scores on a Scale Standard Error 2.0	-4.80 Scores on a Scale Standard Error 1.4	-1.94 Scores on a Scale Standard Error 2.0	-5.69 Scores on a Scale Standard Error 2.0

SECONDARY outcome

Timeframe: Change from baseline at week 6 (Day 43)

Population: Intent-to-treat analysis set

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=8 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=6 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=8 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=17 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=8 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=8 Participants Pooled MIJ821 0.32 mg/kg
Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline	-6.8 Scores on a Scale Standard Deviation 6.606	-4.2 Scores on a Scale Standard Deviation 9.432	-5.4 Scores on a Scale Standard Deviation 7.763	-5.1 Scores on a Scale Standard Deviation 5.651	-2.6 Scores on a Scale Standard Deviation 6.927	-5.4 Scores on a Scale Standard Deviation 4.565

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=10 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly n=9 Participants MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly n=10 Participants Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 Participants Placebo weekly	Pooled MIJ821 0.16 mg/kg n=11 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=10 Participants 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)	-1.50 Scores on a Scale Standard Error 1.0	-2.46 Scores on a Scale Standard Error 1.0	-1.28 Scores on a Scale Standard Error 1.0	-2.33 Scores on a Scale Standard Error 0.7	-2.79 Scores on a Scale Standard Error 0.9	-2.38 Scores on a Scale Standard Error 0.9
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 1.0	-3.43 Scores on a Scale Standard Error 1.1	0.01 Scores on a Scale Standard Error 1.3	-1.97 Scores on a Scale Standard Error 0.7	-2.95 Scores on a Scale Standard Error 1.0	-1.03 Scores on a Scale Standard Error 0.9
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	-2.04 Scores on a Scale Standard Error 1.2	-1.68 Scores on a Scale Standard Error 1.0	-1.59 Scores on a Scale Standard Error 0.7	-1.18 Scores on a Scale Standard Error 1.0	-1.06 Scores on a Scale Standard Error 1.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	MIJ821 0.32 mg/kg Weekly n=9 Participants MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Biweekly MIJ821 0.32 mg/kg biweekly	Ketamine 0.5 mg/kg Weekly Ketamine 0.5 mg/kg weekly	Placebo Weekly Placebo weekly	Pooled MIJ821 0.16 mg/kg n=9 Participants Pooled MIJ821 0.16 mg/kg	Pooled MIJ821 0.32 mg/kg n=9 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)	20.0 Percentage of Participants	—	—	—	40.0 Percentage of Participants	0 Percentage of Participants
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	—	—	—	0 Percentage of Participants	0 Percentage of Participants
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	—	—	—	50.0 Percentage of Participants	0 Percentage of Participants
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	—	—	—	0 Percentage of Participants	0 Percentage of Participants
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	—	—	—	55.6 Percentage of Participants	0 Percentage of Participants
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	—	—	—	33.3 Percentage of Participants	0 Percentage of Participants

Adverse Events

MIJ821 0.16 mg/kg Weekly*

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

MIJ821 0.16 mg/kg Every Other Week

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

MIJ821 0.32 mg/kg Weekly

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

MIJ821 0.32 mg/kg Every Other Week

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Ketamine 0.5 mg/kg Weekly

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo Weekly

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Total

Serious events: 5 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MIJ821 0.16 mg/kg Weekly* n=11 participants at risk MIJ821 0.16 mg/kg weekly\*	MIJ821 0.16 mg/kg Every Other Week n=10 participants at risk MIJ821 0.16 mg/kg every other week	MIJ821 0.32 mg/kg Weekly n=10 participants at risk MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Every Other Week n=9 participants at risk MIJ821 0.32 mg/kg every other week	Ketamine 0.5 mg/kg Weekly n=10 participants at risk Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 participants at risk Placebo weekly	Total n=70 participants at risk Total
Cardiac disorders Atrial fibrillation	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	11.1% 1/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Major depression	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	11.1% 1/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Suicide attempt	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	5.0% 1/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Suicide threat	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	11.1% 1/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/11 • 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.	10.0% 1/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.

Other adverse events

Other adverse events
Measure	MIJ821 0.16 mg/kg Weekly* n=11 participants at risk MIJ821 0.16 mg/kg weekly\*	MIJ821 0.16 mg/kg Every Other Week n=10 participants at risk MIJ821 0.16 mg/kg every other week	MIJ821 0.32 mg/kg Weekly n=10 participants at risk MIJ821 0.32 mg/kg weekly	MIJ821 0.32 mg/kg Every Other Week n=9 participants at risk MIJ821 0.32 mg/kg every other week	Ketamine 0.5 mg/kg Weekly n=10 participants at risk Ketamine 0.5 mg/kg weekly	Placebo Weekly n=20 participants at risk Placebo weekly	Total n=70 participants at risk Total
Cardiac disorders Angina pectoris	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	11.1% 1/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Ear and labyrinth disorders Hyperacusis	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	20.0% 2/10 • 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.	0.00% 0/20 • 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.	2.9% 2/70 • 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.
Eye disorders Asthenopia	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Eye disorders Photophobia	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Eye disorders Vision blurred	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Gastrointestinal disorders Abdominal pain	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	11.1% 1/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Gastrointestinal disorders Dry mouth	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	30.0% 3/10 • 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.	5.0% 1/20 • 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.	5.7% 4/70 • 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.
Gastrointestinal disorders Dyspepsia	0.00% 0/11 • 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.	10.0% 1/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Gastrointestinal disorders Frequent bowel movements	0.00% 0/11 • 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.	10.0% 1/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Gastrointestinal disorders Nausea	0.00% 0/11 • 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.	10.0% 1/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	20.0% 2/10 • 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.	0.00% 0/20 • 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.	5.7% 4/70 • 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.
Gastrointestinal disorders Vomiting	0.00% 0/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
General disorders Fatigue	0.00% 0/11 • 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.	0.00% 0/10 • 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.	20.0% 2/10 • 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.	11.1% 1/9 • 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.	10.0% 1/10 • 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.	5.0% 1/20 • 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.	7.1% 5/70 • 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.
General disorders Feeling abnormal	27.3% 3/11 • 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.	10.0% 1/10 • 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.	20.0% 2/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	8.6% 6/70 • 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.
General disorders Feeling of relaxation	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
General disorders Gait disturbance	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Infections and infestations Gastroenteritis	0.00% 0/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Infections and infestations Oral herpes	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Infections and infestations Upper respiratory tract infection	0.00% 0/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Infections and infestations Urinary tract infection	0.00% 0/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Injury, poisoning and procedural complications Poisoning deliberate	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	11.1% 1/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Investigations Alanine aminotransferase increased	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Investigations Aspartate aminotransferase increased	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Investigations Blood potassium decreased	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Investigations Blood pressure increased	18.2% 2/11 • 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.	10.0% 1/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	4.3% 3/70 • 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.
Investigations Blood pressure systolic increased	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Investigations Gamma-glutamyltransferase increased	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Investigations Platelet count decreased	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/11 • 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.	10.0% 1/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Musculoskeletal and connective tissue disorders Back pain	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Nervous system disorders Akathisia	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Nervous system disorders Amnesia	18.2% 2/11 • 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.	0.00% 0/10 • 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.	50.0% 5/10 • 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.	33.3% 3/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	14.3% 10/70 • 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.
Nervous system disorders Ataxia	0.00% 0/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	22.2% 2/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	4.3% 3/70 • 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.
Nervous system disorders Disturbance in attention	0.00% 0/11 • 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.	10.0% 1/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Nervous system disorders Dizziness	18.2% 2/11 • 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.	30.0% 3/10 • 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.	10.0% 1/10 • 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.	11.1% 1/9 • 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.	20.0% 2/10 • 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.	5.0% 1/20 • 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.	14.3% 10/70 • 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.
Nervous system disorders Dysarthria	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Nervous system disorders Dysgeusia	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Nervous system disorders Headache	9.1% 1/11 • 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.	0.00% 0/10 • 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.	20.0% 2/10 • 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.	11.1% 1/9 • 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.	10.0% 1/10 • 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.	5.0% 1/20 • 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.	8.6% 6/70 • 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.
Nervous system disorders Hypoaesthesia	0.00% 0/11 • 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.	10.0% 1/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	5.0% 1/20 • 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.	2.9% 2/70 • 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.
Nervous system disorders Memory impairment	18.2% 2/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	4.3% 3/70 • 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.
Nervous system disorders Paraesthesia	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	5.0% 1/20 • 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.	4.3% 3/70 • 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.
Nervous system disorders Sciatica	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Nervous system disorders Somnolence	18.2% 2/11 • 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.	10.0% 1/10 • 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.	40.0% 4/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	11.4% 8/70 • 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.
Nervous system disorders Syncope	0.00% 0/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Nervous system disorders Tunnel vision	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Abnormal dreams	0.00% 0/11 • 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.	10.0% 1/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Agitation	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	11.1% 1/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Anxiety	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	11.1% 1/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	2.9% 2/70 • 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.
Psychiatric disorders Confusional state	0.00% 0/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	11.1% 1/9 • 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.	0.00% 0/10 • 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.	5.0% 1/20 • 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.	4.3% 3/70 • 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.
Psychiatric disorders Daydreaming	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	11.1% 1/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Depersonalisation/derealisation disorder	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	50.0% 5/10 • 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.	0.00% 0/20 • 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.	7.1% 5/70 • 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.
Psychiatric disorders Disinhibition	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Dissociation	18.2% 2/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	5.0% 1/20 • 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.	4.3% 3/70 • 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.
Psychiatric disorders Dissociative amnesia	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Euphoric mood	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Illusion	9.1% 1/11 • 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.	10.0% 1/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	2.9% 2/70 • 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.
Psychiatric disorders Insomnia	18.2% 2/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	5.0% 1/20 • 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.	4.3% 3/70 • 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.
Psychiatric disorders Irritability	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Mood swings	0.00% 0/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Sleep disorder	9.1% 1/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Sleep terror	0.00% 0/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Psychiatric disorders Time perception altered	9.1% 1/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	2.9% 2/70 • 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.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/11 • 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.	0.00% 0/10 • 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.	10.0% 1/10 • 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.	0.00% 0/9 • 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.	0.00% 0/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/11 • 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.	0.00% 0/10 • 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.	0.00% 0/10 • 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.	0.00% 0/9 • 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.	10.0% 1/10 • 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.	0.00% 0/20 • 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.	1.4% 1/70 • 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.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER