Trial Outcomes & Findings for Double-Blind, Placebo-Controlled Trial of Ketamine Therapy in Treatment-Resistant Depression (TRD) (NCT NCT01920555)

NCT ID: NCT01920555

Last Updated: 2018-06-19

Results Overview

The HAMD6 is a 6-item clinician-rated scale, where clinicians rate the presence of depression symptoms (i.e., depressed mood, guilt, work and interests, psychomotor retardation, psychic anxiety, somatic symptoms) on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. One item (i.e., somatic symptoms) is rated on only a 3-point scale, ranging from 0-2. The possible scale range is 0-22, where higher values represent more severe depression. This instrument is completed with a structured interview guide by the clinician based on his/her assessment of the patient's symptoms. This structured interview has been validated for use with time frames shorter than one week. In this study, the HAMD6 was used to assess symptoms occurring in the past 24 hours.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 99 participants
• Primary outcome timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1, & 3
• Results posted on: 2018-06-19

Participant Flow

The screening period served as a wash-out period for any prohibited medications that could be discontinued safely. Discontinuation of medications were discussed in consultation with the prescribing clinician.

Participant milestones

Measure	Ketamine 0.1mg Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam (Active Placebo) Patients in this arm will receive 0.045 mg/kg of midazolam - one single infusion Placebo Midazolam: Dose of Midazolam (active placebo) will be 0.045 mg/kg - one single infusion
Overall Study STARTED	18	20	22	20	19
Overall Study COMPLETED	14	16	21	17	18
Overall Study NOT COMPLETED	4	4	1	3	1

Reasons for withdrawal

Measure	Ketamine 0.1mg Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam (Active Placebo) Patients in this arm will receive 0.045 mg/kg of midazolam - one single infusion Placebo Midazolam: Dose of Midazolam (active placebo) will be 0.045 mg/kg - one single infusion
Overall Study Physician Decision	1	2	1	2	0
Overall Study Lack of Efficacy	2	0	0	0	0
Overall Study Travel Difficulties	1	1	0	0	1
Overall Study Lost to Follow-up	0	1	0	1	0

Baseline Characteristics

Double-Blind, Placebo-Controlled Trial of Ketamine Therapy in Treatment-Resistant Depression (TRD)

Baseline characteristics by cohort

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam (Active Placebo) n=19 Participants Patients in this arm will receive 0.045 mg/kg of midazolam - one single infusion Placebo Midazolam: Dose of Midazolam (active placebo) will be 0.045 mg/kg - one single infusion	Total n=99 Participants Total of all reporting groups
Age, Continuous	43.1 years STANDARD_DEVIATION 11.9 • n=5 Participants	45.5 years STANDARD_DEVIATION 14.6 • n=7 Participants	48.6 years STANDARD_DEVIATION 12.9 • n=5 Participants	47.4 years STANDARD_DEVIATION 10.1 • n=4 Participants	45.6 years STANDARD_DEVIATION 13.8 • n=21 Participants	46.04 years STANDARD_DEVIATION 12.64 • n=8 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants	8 Participants n=4 Participants	11 Participants n=21 Participants	49 Participants n=8 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	12 Participants n=4 Participants	8 Participants n=21 Participants	50 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	20 Participants n=4 Participants	19 Participants n=21 Participants	96 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
BMI	25.2 kg/m^2 STANDARD_DEVIATION 3.1 • n=5 Participants	24.9 kg/m^2 STANDARD_DEVIATION 3.7 • n=7 Participants	25.3 kg/m^2 STANDARD_DEVIATION 5.7 • n=5 Participants	26.1 kg/m^2 STANDARD_DEVIATION 3.8 • n=4 Participants	26.3 kg/m^2 STANDARD_DEVIATION 4.1 • n=21 Participants	24.96 kg/m^2 STANDARD_DEVIATION 4.08 • n=8 Participants
Abnormal and Clinically Significant Labs CBC	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Abnormal and Clinically Significant Labs Chemistry	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Abnormal and Clinically Significant Labs Hormonal Measures (testosterone, SHBG, Free T)	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants
Abnormal and Clinically Significant Labs Hormonal Measures (DHEA)	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Abnormal and Clinically Significant Labs Hormonal Measures (remaining tests)	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Abnormal and Clinically Significant Labs Pregnancy Test	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Abnormal and Clinically Significant Labs Urine Toxicology Screen	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants

PRIMARY outcome

Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1, & 3

Population: Several subjects dropped out of the study in between Day 0, Day 1 and Day 3.

The HAMD6 is a 6-item clinician-rated scale, where clinicians rate the presence of depression symptoms (i.e., depressed mood, guilt, work and interests, psychomotor retardation, psychic anxiety, somatic symptoms) on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. One item (i.e., somatic symptoms) is rated on only a 3-point scale, ranging from 0-2. The possible scale range is 0-22, where higher values represent more severe depression. This instrument is completed with a structured interview guide by the clinician based on his/her assessment of the patient's symptoms. This structured interview has been validated for use with time frames shorter than one week. In this study, the HAMD6 was used to assess symptoms occurring in the past 24 hours.

Outcome measures

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam 0.045mg n=19 Participants Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion
Hamilton Rating Scale for Depression - 6 Items Day 0	12.5555556 units on a scale Standard Deviation 1.8221585	12.7500000 units on a scale Standard Deviation 2.4894514	12.5909091 units on a scale Standard Deviation 1.4690162	12.6315789 units on a scale Standard Deviation 2.0872770	13.0526316 units on a scale Standard Deviation 2.2967050
Hamilton Rating Scale for Depression - 6 Items Day 1	7.5000000 units on a scale Standard Deviation 4.3204938	9.2631579 units on a scale Standard Deviation 3.6944719	5.8636364 units on a scale Standard Deviation 4.4859087	6.9000000 units on a scale Standard Deviation 4.5061362	10.6666667 units on a scale Standard Deviation 3.3606722
Hamilton Rating Scale for Depression - 6 Items Day 3	6.8000000 units on a scale Standard Deviation 4.6167397	8.4736842 units on a scale Standard Deviation 4.9818384	5.9047619 units on a scale Standard Deviation 4.3000554	7.2000000 units on a scale Standard Deviation 3.8196170	9.0555556 units on a scale Standard Deviation 4.5435439

SECONDARY outcome

Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0 and 3.

Population: Several subjects dropped out of the study in between Day 0, Day 1 and Day 3.

The MADRS is a 10-item clinician-rated scale measuring depression severity. Symptoms are rated on a 7-point scale, where 0 = "not present", and 1-6 represent increasing severity. Values 2, 4, and 6 have specific anchoring text (e.g., 2="Difficulties in starting activities." 4="Difficulties in starting simple routine activities which are carried out with effort, 6="Complete lassitude. Unable to do anything without help.") Values 1, 3, and 5 do not have specific text. The possible scale range is 0-60, where higher values represent higher severity. In this study, the MADRS was used to rate symptoms occurring in the past 3 days.

Outcome measures

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam 0.045mg n=19 Participants Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion
Montgomery-Asberg Depression Rating Scale (MADRS) Day 0	33.8333333 units on a scale Standard Deviation 5.9334545	34.4500000 units on a scale Standard Deviation 8.4571676	31.5909091 units on a scale Standard Deviation 3.9359042	32.6500000 units on a scale Standard Deviation 5.8873191	33.6315789 units on a scale Standard Deviation 7.0884141
Montgomery-Asberg Depression Rating Scale (MADRS) Day 3	19.6666667 units on a scale Standard Deviation 10.8144524	22.6315789 units on a scale Standard Deviation 11.7294052	14.7619048 units on a scale Standard Deviation 8.9883523	17.1000000 units on a scale Standard Deviation 11.5708345	24.8333333 units on a scale Standard Deviation 10.5286723

SECONDARY outcome

Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3

Population: Several subjects dropped out of the study in between Day 0, Day 1 and Day 3.

The CGI-S is a clinician rated single-item scale: "How depressed is the patient at this time?", rated on a 7-point response scale: 1 = Normal, not at all depressed, 2 = Borderline depressed, 3 = Mildly depressed, 4 = Moderately depressed. 5 = Markedly depressed, 6 = severely depressed, 7 = Among the most severely depressed patients. When rating patients, clinicians were asked to consider the past 24 hours.

Outcome measures

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam 0.045mg n=19 Participants Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion
Clinical Global Impressions-Severity (CGI-S) Day 1	3.5625000 units on a scale Standard Deviation 1.4591664	4.2631579 units on a scale Standard Deviation 1.2401660	3.2727273 units on a scale Standard Deviation 1.2792043	3.5000000 units on a scale Standard Deviation 1.1002392	4.555556 units on a scale Standard Deviation 0.7838234
Clinical Global Impressions-Severity (CGI-S) Day 3	3.4000000 units on a scale Standard Deviation 1.6388149	3.7368421 units on a scale Standard Deviation 1.4848159	3.1428571 units on a scale Standard Deviation 1.3887301	3.3000000 units on a scale Standard Deviation 1.4545754	4.1666667 units on a scale Standard Deviation 1.3394468
Clinical Global Impressions-Severity (CGI-S) Day 0	5.0000000 units on a scale Standard Deviation 0.7669650	5.2000000 units on a scale Standard Deviation 0.6958524	4.8636364 units on a scale Standard Deviation 0.6396021	5.2000000 units on a scale Standard Deviation 0.7677719	5.000000 units on a scale Standard Deviation 0.7453560

SECONDARY outcome

Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3

Population: Several subjects dropped out of the study in between Day 0, Day 1 and Day 3.

The CGI-I is a clinician rated single-item scale: "Compared to the patient's condition at admission, how much has the patient changed?", rated on a 7-point response scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, and 7 = Very much worse. In this case, "admission" referred to the CGI-S screening assessments performed between Day -28 an -7, one conducted during the screening visit, and a second rating conducted by a remote, independent rater.

Outcome measures

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam 0.045mg n=19 Participants Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion
Clinical Global Impressions-Improvement (CGI-I) Scale Day 0	3.8888889 units on a scale Standard Deviation 0.3233808	4.0500000 units on a scale Standard Deviation 0.2236068	4.1363636 units on a scale Standard Deviation 0.7101613	4.0000000 units on a scale Standard Deviation 0.4588315	4.1578947 units on a scale Standard Deviation 0.6021404
Clinical Global Impressions-Improvement (CGI-I) Scale Day 1	3.0625000 units on a scale Standard Deviation 1.4361407	3.3684211 units on a scale Standard Deviation 1.0651305	2.6363636 units on a scale Standard Deviation 0.9021379	3.0500000 units on a scale Standard Deviation 1.2343760	3.6111111 units on a scale Standard Deviation 0.6076850
Clinical Global Impressions-Improvement (CGI-I) Scale Day 3	2.9333333 units on a scale Standard Deviation 1.2798809	2.8421053 units on a scale Standard Deviation 1.2588865	2.5714286 units on a scale Standard Deviation 0.9258201	2.5500000 units on a scale Standard Deviation 1.0990426	3.1666667 units on a scale Standard Deviation 1.0431852

SECONDARY outcome

Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3

Population: Several subjects dropped out of the study in between Day 0, Day 1 and Day 3.

The SDQ is a 44-item self-report scale, which aims to measure depression more comprehensively by including the assessment of symptoms in the anxiety-depression spectrum, including symptoms of irritability, anger attacks, and anxiety. Items are rated on an 6-point Likert scale, where participants are asked to rate if a specific symptom (e.g. "How has your mood been over the past 24 hours?") is normal for him or her (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). The total scale score is calculated by averaging across the items, resulting in a possible range from 1 to 6. Higher scores indicate greater depression severity. When rating, patients were asked to consider their symptoms during the past 24 hours.

Outcome measures

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam 0.045mg n=19 Participants Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion
Symptoms of Depression Questionnaire (SDQ) Day 0	3.5164141 units on a scale Standard Deviation 0.5081856	3.4636364 units on a scale Standard Deviation 0.5416735	3.5392562 units on a scale Standard Deviation 0.5838397	3.4113636 units on a scale Standard Deviation 0.4336652	3.4264507 units on a scale Standard Deviation 0.4719770
Symptoms of Depression Questionnaire (SDQ) Day 1	2.5752843 units on a scale Standard Deviation 0.7091841	2.9096195 units on a scale Standard Deviation 0.7123910	2.3109504 units on a scale Standard Deviation 0.6315677	2.6113636 units on a scale Standard Deviation 0.500567	2.9200573 units on a scale Standard Deviation 0.6464210
Symptoms of Depression Questionnaire (SDQ) Day 3	2.5106061 units on a scale Standard Deviation 0.7158120	2.7828283 units on a scale Standard Deviation 0.7398734	2.5573593 units on a scale Standard Deviation 0.9017779	2.5909091 units on a scale Standard Deviation 0.5736341	2.8751353 units on a scale Standard Deviation 0.6668931

SECONDARY outcome

Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3

Population: Several subjects dropped out of the study in between Day 0, Day 1 and Day 3.

The CPAS is a 16-item self-report scale to assess the level to which participants experience persistent distress due to feeling that they have not returned to their normal or premorbid state. Items (e.g., "I look forward to things") are rated on a 5-point scale (0=not at all, 1=very much less than normal, 2=much less than normal, 3=slightly less than normal, 4=same as best or normal self). The possible scale range is 0 to 64, with higher scores indicating greater recovery from depression. Patients were asked to rate their experience of the past 24 hours.

Outcome measures

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam 0.045mg n=19 Participants Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion
Clinical Positive Affect Scale (CPAS) Day 0	19.3333333 units on a scale Standard Deviation 12.1896774	20.5000000 units on a scale Standard Deviation 15.4357753	20.6363636 units on a scale Standard Deviation 11.7008158	21.2500000 units on a scale Standard Deviation 14.6785737	21.2631579 units on a scale Standard Deviation 12.1052886
Clinical Positive Affect Scale (CPAS) Day 1	35.2500000 units on a scale Standard Deviation 20.9936498	27.0526316 units on a scale Standard Deviation 18.8516833	40.8696964 units on a scale Standard Deviation 19.5284785	33.0000000 units on a scale Standard Deviation 16.2642650	24.4444444 units on a scale Standard Deviation 15.2053482
Clinical Positive Affect Scale (CPAS) Day 3	38.8666667 units on a scale Standard Deviation 22.8666667	28.3888889 units on a scale Standard Deviation 20.2459550	39.7619048 units on a scale Standard Deviation 22.5319878	37.4500000 units on a scale Standard Deviation 18.7096232	33.3750000 units on a scale Standard Deviation 15.8445574

SECONDARY outcome

Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3

Population: Several subjects dropped out of the study in between Day 0, Day 1 and Day 3.

The SHAPS is a 14-item self-report scale to measure hedonic tone. Items (e.g., "I would enjoy reading a book, magazine, or newspaper.") are rated on a 4-point scale (1=strongly disagree, 2=disagree, 3=agree, 4=strongly agree). Either of the 'disagree' responses scores 1 point, and either of the 'agree' responses scores 0 points, for a total scale range of 0-14. Higher scores indicate greater inability to experience pleasure. Patients were asked to rate their experience of the past 24 hours.

Outcome measures

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam 0.045mg n=19 Participants Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion
Snaith-Hamilton Pleasure-Scale (SHAPS) Day 0	7.2222222 units on a scale Standard Deviation 3.9040786	7.5500000 units on a scale Standard Deviation 3.9132030	6.5909091 units on a scale Standard Deviation 3.2316749	7.3500000 units on a scale Standard Deviation 4.1961762	6.4736842 units on a scale Standard Deviation 3.7471237
Snaith-Hamilton Pleasure-Scale (SHAPS) Day 1	3.9375000 units on a scale Standard Deviation 4.2812576	5.7368421 units on a scale Standard Deviation 4.2536534	2.22727273 units on a scale Standard Deviation 3.5748036	4.3000000 units on a scale Standard Deviation 4.5664682	5.0000000 units on a scale Standard Deviation 4.6272848
Snaith-Hamilton Pleasure-Scale (SHAPS) Day 3	3.5333333 units on a scale Standard Deviation 3.3777987	6.3888889 units on a scale Standard Deviation 4.5262488	3.0000000 units on a scale Standard Deviation 3.7815341	3.6500000 units on a scale Standard Deviation 4.8370826	4.2500000 units on a scale Standard Deviation 3.8384024

SECONDARY outcome

Timeframe: Day 0/baseline at 0, 40, 80, and 120 minutes

The CADSS is a 23-item self-report scale for the assessment of dissociative states. It is a reliable, valid self-report instrument. The severity of each dissociative symptom ranges from 0 (not present) to 4 (extreme). The total score is calculated by summing across items, with a total possible range of 0-92. The CADSS was administered right before infusion, and 40, 80 minute and 120 minutes after the start of infusion. The timeframe is "at this moment".

Outcome measures

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam 0.045mg n=19 Participants Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion
Clinician-Administered Dissociative States Scale (CADSS) Scores During Infusion Minute 0	0.1111111 units on a scale Standard Deviation 0.4714045	0.1000000 units on a scale Standard Deviation 0.4472136	0 units on a scale Standard Deviation 0	0.1000000 units on a scale Standard Deviation 0.3077935	0.4210526 units on a scale Standard Deviation 1.01739326
Clinician-Administered Dissociative States Scale (CADSS) Scores During Infusion Minute 40	3.0000000 units on a scale Standard Deviation 5.0758946	4.0500000 units on a scale Standard Deviation 4.2608993	14.2727273 units on a scale Standard Deviation 9.6076644	24.6842105 units on a scale Standard Deviation 17.7108022	2.6842105 units on a scale Standard Deviation 3.5127171
Clinician-Administered Dissociative States Scale (CADSS) Scores During Infusion Minute 80	0.4444444 units on a scale Standard Deviation 0.7838234	0.1000000 units on a scale Standard Deviation 0.4472136	0.7727273 units on a scale Standard Deviation 2.1141658	1.8000000 units on a scale Standard Deviation 2.9664794	1.1578947 units on a scale Standard Deviation 1.8337320
Clinician-Administered Dissociative States Scale (CADSS) Scores During Infusion Minute 120	0.0555556 units on a scale Standard Deviation 0.2357023	0 units on a scale Standard Deviation 0	0.1363636 units on a scale Standard Deviation 0.6396021	0.6500000 units on a scale Standard Deviation 1.5985191	0.5789474 units on a scale Standard Deviation 0.9015905

SECONDARY outcome

Timeframe: Screening Visit and Days 0, 1, 3, 5, 7, 14 and 30 combined

The Columbia Suicide Severity Rating Scale (C-SSRS): The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed in the National Institute of Mental Health Treatment of Adolescent Suicide Attempters Study to assess severity and track suicidal events through any treatment. It is a clinical interview providing a summary of both ideation and behavior that can be administered during any evaluation or risk assessment to identify the level and type of suicidality present. The C-SSRS can also be used during treatment to monitor for clinical worsening or improvement. It contains 5 rating scale questions (yes/no) for suicidal ideation increasing severity and 5 rating scale questions (yes/no) for suicidal behavior of increasing severity. The time frame is for both lifetime and the past six months for the Baseline/Screening scale and since the last visit for the Since Last Visit scale.

Outcome measures

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam 0.045mg n=19 Participants Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion
Number of Participants Reporting Suicidal Ideation/Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) Screening: # with suicidal ideation/behavior	17 Participants	15 Participants	17 Participants	14 Participants	17 Participants
Number of Participants Reporting Suicidal Ideation/Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) Follow-Up: # with suicidal ideation/behavior	15 Participants	9 Participants	10 Participants	6 Participants	13 Participants

SECONDARY outcome

Timeframe: Day 3 and Early Termination Visit (approximately 3 weeks following intervention)

1. CBC

2. Chemistry (Total bilirubin, AST, ALT, GGT, ALK Phosphatase, Creatinine, BUN/Urea, Glucose, Uric Acid)

Testing was performed by study site laboratories and used institutional normal lab value ranges.

Outcome measures

Measure	Ketamine 0.1mg n=18 Participants Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 Participants Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 Participants Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 Participants Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam 0.045mg n=19 Participants Patients in this arm will receive 0.045 mg/kg of Midazolam (active placebo) - one single infusion
Number of Participants With Abnormal and Clinically Significant CBC and Chemistry Labs by Treatment Chemistry Remaining Tests	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal and Clinically Significant CBC and Chemistry Labs by Treatment Chemistry ALT(SGPT)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal and Clinically Significant CBC and Chemistry Labs by Treatment Chemistry AST(SGOT)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal and Clinically Significant CBC and Chemistry Labs by Treatment Chemistry Total Bilirubin	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal and Clinically Significant CBC and Chemistry Labs by Treatment CBC	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Ketamine 0.1mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Ketamine 0.2mg

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Ketamine 0.5mg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Ketamine 1.0mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Midazolam (Active Placebo)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ketamine 0.1mg n=18 participants at risk Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 participants at risk Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 participants at risk Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 participants at risk Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam (Active Placebo) n=19 participants at risk Patients in this arm will receive 0.045 mg/kg of midazolam - one single infusion Placebo Midazolam: Dose of Midazolam (active placebo) will be 0.045 mg/kg - one single infusion
Psychiatric disorders Suicide Attempt	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of events 1 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.

Other adverse events

Measure	Ketamine 0.1mg n=18 participants at risk Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.1 mg/kg - one single infusion	Ketamine 0.2mg n=20 participants at risk Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.2 mg/kg - one single infusion	Ketamine 0.5mg n=22 participants at risk Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 0.5 mg/kg - one single infusion	Ketamine 1.0mg n=20 participants at risk Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion Ketamine: Dose of Ketamine will be 1.0 mg/kg - one single infusion	Midazolam (Active Placebo) n=19 participants at risk Patients in this arm will receive 0.045 mg/kg of midazolam - one single infusion Placebo Midazolam: Dose of Midazolam (active placebo) will be 0.045 mg/kg - one single infusion
Nervous system disorders Headache	16.7% 3/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	10.0% 2/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	15.0% 3/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Gastrointestinal disorders Nausea	11.1% 2/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	13.6% 3/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	15.0% 3/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Gastrointestinal disorders Vomiting	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Depression	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Gastrointestinal disorders Dyspepsia	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	10.0% 2/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Abnormal Dreams	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.3% 1/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Musculoskeletal and connective tissue disorders Back Pain	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.3% 1/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Cardiac disorders Blood Pressure Increase	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	10.0% 2/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Gastrointestinal disorders Diarrhea	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Insomnia	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.3% 1/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Musculoskeletal and connective tissue disorders Pain In Extremity	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Poor Quality Sleep	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Suicidal Ideation	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Cardiac disorders Tachycardia	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Infections and infestations Tooth Abscess	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.3% 1/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Nervous system disorders Asthenia	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Reproductive system and breast disorders Blood Testosterone	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.3% 1/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Skin and subcutaneous tissue disorders Dermatitis Contact	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Dissociation	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
General disorders Dizziness	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Injury, poisoning and procedural complications Exposure to Toxic Agent	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Injury, poisoning and procedural complications Fall	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Vascular disorders Flushing	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Infections and infestations Gastroenteritis Viral	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.3% 1/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Hepatobiliary disorders Hepatic Enzyme Increased	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Vascular disorders Hot Flush	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Cardiac disorders Hypertension	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Gastrointestinal disorders Increased Appetite	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Initial Insomnia	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.3% 1/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Intentional Self-Injury	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.3% 1/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Nervous system disorders Loss of Consciousness	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Malaise	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Overdose	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
General disorders Presyncope	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Infections and infestations Respiratory Tract Infection	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Psychiatric disorders Self Injurious Behavior	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.3% 1/19 • Number of events 1 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Infections and infestations Sinusitis	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.3% 1/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Vascular disorders Vertigo	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	4.5% 1/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Infections and infestations Viral Upper Respiratory Tract Infection	0.00% 0/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	5.0% 1/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.
Blood and lymphatic system disorders White Blood Cell Count Decreased	5.6% 1/18 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/22 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/20 • Number of patients with adverse events post infusion (treatment) up to 30 days.	0.00% 0/19 • Number of patients with adverse events post infusion (treatment) up to 30 days.

Additional Information

Maurizio Fava, MD

Massachusetts General Hospital

Phone: 617-724-2513

Email: MFAVA@mgh.harvard.edu

Results disclosure agreements

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