For patients randomly assigned to the placebo/ placebo sequence, study medication will be placebo during the first phase (3 days) and during the second phase (3 days).

For patients randomly assigned to the placebo/low-dose drug sequence, the patient will receive placebo for 3 days and then 10 mg/day CERC-501 for the following 3 days.

For patients randomly assigned to the placebo/high-dose drug sequence, the patient will receive placebo for 3 days and then 20 mg/day CERC-501 for the following 3 days.

Compare response rates at 72 hours for of patients treated with either dose (10 mg/day or 20 mg/day) of CERC-501 to those assigned to placebo therapy, using the Sequential Parallel Comparison Design (SPCD), with response defined as a 50% or greater reduction from baseline to Day 3 on the HAM-D-6 total score).

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

The HAM-D-6 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. Scale items are assessed based on symptoms within the past 24 hours. A higher score indicates more depression symptoms.

The 10-item Montgomery-Asberg Depression Rating Scale (MADRS), which measures depression severity (in past 3 days), was completed by clinicians using an MGH structured interview. Each item is measured on a scale from 0 to 6, and the items are summed to find the total score. The total minimum score is 0 units on a scale and the total maximum score is 60 units on a scale, where higher scores indicate more severe depression.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

The CGI-S scale was administered by clinicians to measure depressive severity (CGI-S). Each item is rated on a seven-point scale (1=normal to 7=among the most severe), so a higher total score indicates greater depressive severity. Severity is assessed based on the last 24 hours.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

The CGI-I scale was administered by clinicians to measure improvement in depressive severity (CGI-I). Each item is rated on a seven-point scale (1=very much improved to 7=very much worse), so a higher total score indicates less improvement in depressive severity. Improvement is assessed based on the last 24 hours.

This validated self-rating instrument has 44 items on a scale of 1-6, measuring multiple depressive symptom domains. Each item is rated based on a subject's perception of what is normal for the individual (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). This scale is rated based on the past 24 hours. A total score is calculated by summing the 44 item scores, for a range of 0-264.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

This is a 10-item, validated, self-rated measure of perceived stress, that is of the degree to which the subjects perceives things to be stressful and overwhelming. Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress. Scores ranging from 0-13 would be considered low stress. Scores ranging from 14-26 would be considered moderate stress. Scores ranging from 27-40 would be considered high perceived stress. This scale is rated based on the past 24 hours.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

This is a validated, self-rated measure of positive affect uses 5-point scales (1 = very slightly/not at all to 5 = extremely). Higher scores represent higher levels of positive affect. The scale is rated based on the past 24 hours. The total score is the sum of 10 items, for a range of 10-50.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

These are two well-validated 7-item self-rating scales that measure social health. A higher score represents higher satisfaction on each scale. The scales are rated based on the past 24 hours. Each item is rated 1-5 (1=Not at all, 2=A little bit, 3=Somewhat, 4=Quite a bit, 5=Very much). Each 7-item subscale score is the sum of each of the 7 items and ranges from 7-35.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior. 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 will be performed to assess suicidal ideation and behavior. It contains a 5-item rating scale for suicidal ideation and a 7-item rating scale for suicidal behavior. Higher total scores indicate higher severity. Each item is coded 1=yes, 0=no, so a total score of 0 on each scale means that a no response was entered for each of the 5 suicidal ideation and for each of the 7 suicidal behavior questions, i.e., 0=lowest severity score. Total suicidal ideation score ranges from 0 (least severe) to 5 (most severe). Total suicidal behavior score ranges from 0 (least severe) to 7 (most severe).

Number of Participants with clinically significant abnormal electrocardiogram (ECG)

Total number of participants with clinically significant abnormal labs

Patients in this arm will receive placebo for 3 days (in Phase 1) and CERC-501 10.0 mg/day for 3 days (in Phase 2)

CERC-501: Low dose of CERC-501 will be 10 mg/day during the first phase (3 days) and during the second phase (3 days).

Patients in this arm will receive placebo for 3 days (in Phase 1) and CERC-501 20.0 mg/day for 3 days (in Phase 2)

CERC-501: High Dose of CERC-501 will be 20 mg/day during the first phase (3 days) and during the second phase (3 days).

Patients in this arm will receive placebo for 3 days (in Phase 1) and for 3 subsequent days (in Phase 2)

Total of all reporting groups

Placebo therapy; pooled those on placebo in phase 1 with those on placebo in phase 2 who were placebo non-responders from phase 1.

Response is defined as a 50% or greater reduction from baseline to Day 3 on the Hamilton Rating Scale for Depression - 6 Items (HAM-D-6) total score and a Montgomery-Asberg Depression Rating Scale (MADRS) score of 16 or more at day 3.

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. Scale items are assessed based on symptoms within the past 24 hours. A higher score indicates more depression symptoms. Total scores range from 0 (normal) to 22 (severe).

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

The 20-day follow-up analyses only use drug-drug (either dose) and placebo-placebo arms. 2 participants were in low dose drug-drug arm, 2 participants were in high dose drug-drug arm, and 1 participant was in the placebo-placebo arm. One drug-drug pt missing day 20 data.

Compare response rates at 72 hours for of patients treated with either dose (10 mg/day or 20 mg/day) of CERC-501 to those assigned to placebo therapy, using the Sequential Parallel Comparison Design (SPCD), with response defined as a 50% or greater reduction from baseline to Day 3 on the HAM-D-6 total score).

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

The HAM-D-6 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. Scale items are assessed based on symptoms within the past 24 hours. A higher score indicates more depression symptoms.

In the sequential parallel comparison design (SPCD) analyses through 72 hours, placebo non-responder data is included from phase 2 and is pooled with phase 1 data. All placebo participants from phase 1 were non-responders based on HAM-D-6 reduction and MADRS criteria.

The 10-item Montgomery-Asberg Depression Rating Scale (MADRS), which measures depression severity (in past 3 days), was completed by clinicians using an MGH structured interview. Each item is measured on a scale from 0 to 6, and the items are summed to find the total score. The total minimum score is 0 units on a scale and the total maximum score is 60 units on a scale, where higher scores indicate more severe depression.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

In the sequential parallel comparison design (SPCD) analyses through 72 hours, placebo non-responder data is included from phase 2 and is pooled with phase 1 data. All placebo participants from phase 1 were non-responders based on HAM-D-6 and MADRS criteria. The 20-day follow-up analyses only use drug-drug (either dose) and placebo-placebo arms.

The CGI-S scale was administered by clinicians to measure depressive severity (CGI-S). Each item is rated on a seven-point scale (1=normal to 7=among the most severe), so a higher total score indicates greater depressive severity. Severity is assessed based on the last 24 hours.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

In the sequential parallel comparison design (SPCD) analyses through 72 hours, placebo non-responder data is included from phase 2 and is pooled with phase 1 data. All placebo participants from phase 1 were non-responders based on HAM-D-6 and MADRS criteria. The 20-day follow-up analyses only use drug-drug (either dose) and placebo-placebo arms.

The CGI-I scale was administered by clinicians to measure improvement in depressive severity (CGI-I). Each item is rated on a seven-point scale (1=very much improved to 7=very much worse), so a higher total score indicates less improvement in depressive severity. Improvement is assessed based on the last 24 hours.

In the sequential parallel comparison design (SPCD) analyses through 72 hours, placebo non-responder data is included from phase 2 and is pooled with phase 1 data. All placebo participants from phase 1 were non-responders based on HAM-D-6 and MADRS criteria.The 20-day follow-up analyses only use drug-drug (either dose) and placebo-placebo arms.

This validated self-rating instrument has 44 items on a scale of 1-6, measuring multiple depressive symptom domains. Each item is rated based on a subject's perception of what is normal for the individual (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). This scale is rated based on the past 24 hours. A total score is calculated by summing the 44 item scores, for a range of 0-264.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

In the sequential parallel comparison design (SPCD) analyses through 72 hours, placebo non-responder data is included from phase 2 and is pooled with phase 1 data. All placebo participants from phase 1 were non-responders based on HAM-D-6 and MADRS criteria. The 20-day follow-up analyses only use drug-drug (either dose) and placebo-placebo arms.

This is a 10-item, validated, self-rated measure of perceived stress, that is of the degree to which the subjects perceives things to be stressful and overwhelming. Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress. Scores ranging from 0-13 would be considered low stress. Scores ranging from 14-26 would be considered moderate stress. Scores ranging from 27-40 would be considered high perceived stress. This scale is rated based on the past 24 hours.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

In the sequential parallel comparison design (SPCD) analyses through 72 hrs, placebo non-responders are included from phase 2 and are pooled with phase 1. All placebo participants from phase 1 were non-responders based on HAM-D-6 and MADRS criteria. 2 pts missing 72-hr PSS values. The 20-day analyses only use drug-drug and placebo-placebo arms.

This is a validated, self-rated measure of positive affect uses 5-point scales (1 = very slightly/not at all to 5 = extremely). Higher scores represent higher levels of positive affect. The scale is rated based on the past 24 hours. The total score is the sum of 10 items, for a range of 10-50.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

In the sequential parallel comparison design (SPCD) analyses through 72 hrs, placebo non-responder data is included from phase 2 and is pooled with phase 1. All phase 1 placebo participants were non-responders based on HAM-D-6 and MADRS criteria.The 20-day analyses only use drug-drug (either dose) and placebo-placebo arms. 1 pt missing PAS data.

These are two well-validated 7-item self-rating scales that measure social health. A higher score represents higher satisfaction on each scale. The scales are rated based on the past 24 hours. Each item is rated 1-5 (1=Not at all, 2=A little bit, 3=Somewhat, 4=Quite a bit, 5=Very much). Each 7-item subscale score is the sum of each of the 7 items and ranges from 7-35.

To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

In the sequential parallel comparison design (SPCD) analyses through 72 hours, placebo non-responder data is included from phase 2 and is pooled with phase 1 data. All placebo participants from phase 1 were non-responders based on HAM-D-6 and MADRS criteria.The 20-day follow-up analyses only use drug-drug (either dose) and placebo-placebo arms.

The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior. 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 will be performed to assess suicidal ideation and behavior. It contains a 5-item rating scale for suicidal ideation and a 7-item rating scale for suicidal behavior. Higher total scores indicate higher severity. Each item is coded 1=yes, 0=no, so a total score of 0 on each scale means that a no response was entered for each of the 5 suicidal ideation and for each of the 7 suicidal behavior questions, i.e., 0=lowest severity score. Total suicidal ideation score ranges from 0 (least severe) to 5 (most severe). Total suicidal behavior score ranges from 0 (least severe) to 7 (most severe).

In the sequential parallel comparison design (SPCD) analyses through 72 hours, placebo non-responder data is included from phase 2 and is pooled with phase 1 data. All placebo participants from phase 1 were non-responders based on HAM-D-6 reduction and MADRS criteria. 1 CERC-501 pt and 3 placebo pts are missing data on 72-hr change values.

Number of Participants with clinically significant abnormal electrocardiogram (ECG)

In the sequential parallel comparison design (SPCD) analyses through 72 hours, placebo non-responder data is included from phase 2 and is pooled with phase 1 data. All placebo participants from phase 1 were non-responders based on HAM-D-6 reduction and MADRS criteria.

Total number of participants with clinically significant abnormal labs

In the sequential parallel comparison design (SPCD) analyses through 72 hours, placebo non-responder data is included from phase 2 and is pooled with phase 1 data. All placebo participants from phase 1 were non-responders based on HAM-D-6 reduction and MADRS criteria.

Patients receive CERC-501 20.0 mg/day

Patients receive placebo