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Proof-of-Concept Trial of CERC-501 Augmentation of Antidepressant Therapy in Treatment-Resistant Depression (RAPID KOR)

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ClinicalTrials.gov Identifier: NCT01913535
Recruitment Status : Terminated (slow enrollment)
First Posted : August 1, 2013
Results First Posted : July 2, 2017
Last Update Posted : July 2, 2017
Sponsor:
Collaborators:
National Institute of Mental Health (NIMH)
Butler Hospital
Rush University
Temple University
University of Kansas
Information provided by (Responsible Party):
Maurizio Fava, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Treatment Resistant Depression
Interventions Drug: CERC-501
Drug: Placebo
Enrollment 8

Recruitment Details  
Pre-assignment Details Only 8 participants were randomized because the study terminated early due to slow enrollment.
Arm/Group Title Low Dose Drug-Drug Arm High Dose Drug-Drug Arm Placebo/Low-Dose Drug Arm Placebo/High-Dose Drug Arm Placebo/Placebo Arm
Hide Arm/Group Description

Patients in this arm will receive CERC-501 10.0 mg/day for 3 days (in Phase 1) and for 3 subsequent 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 CERC-501 20.0 mg/day for 3 days (in Phase 1) and for 3 subsequent 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 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).

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.

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)

Placebo: 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).

Period Title: Phase 1 (Days 0-2)
Started 2 2 1 2 1
Completed 2 2 1 2 1
Not Completed 0 0 0 0 0
Period Title: Phase 2 (Days 3-5)
Started 2 2 1 2 1
Completed 2 2 1 2 1
Not Completed 0 0 0 0 0
Arm/Group Title Low Dose Drug-Drug Arm High Dose Drug-Drug Arm Placebo/Low-Dose Drug Arm Placebo/High-Dose Drug Arm Placebo/Placebo Arm Total
Hide Arm/Group Description

Patients in this arm will receive CERC-501 10.0 mg/day for 3 days (in Phase 1) and for 3 subsequent 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 CERC-501 20.0 mg/day for 3 days (in Phase 1) and for 3 subsequent 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 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
Overall Number of Baseline Participants 2 2 1 2 1 8
Hide Baseline Analysis Population Description
Only 8 participants were randomized because the study terminated early due to slow enrollment.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 2 participants 2 participants 1 participants 2 participants 1 participants 8 participants
58.2
(52.1 to 64.4)
58.3
(58.0 to 58.5)
34.5
(34.5 to 34.5)
36.3
(27.2 to 45.4)
38.8
(38.8 to 38.8)
48.8
(27.2 to 64.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 1 participants 2 participants 1 participants 8 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
2
 100.0%
2
 100.0%
1
 100.0%
2
 100.0%
1
 100.0%
8
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 1 participants 2 participants 1 participants 8 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
2
 100.0%
2
 100.0%
1
 100.0%
2
 100.0%
1
 100.0%
8
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 1 participants 2 participants 1 participants 8 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
2
 100.0%
2
 100.0%
1
 100.0%
2
 100.0%
1
 100.0%
8
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 2 participants 2 participants 1 participants 2 participants 1 participants 8 participants
2
 100.0%
2
 100.0%
1
 100.0%
2
 100.0%
1
 100.0%
8
 100.0%
1.Primary Outcome
Title Change in Hamilton Rating Scale for Depression - 6 Items (HAM-D-6)
Hide Description

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.

Time Frame Baseline and 72 hours after initiating treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

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.

Overall Number of Participants Analyzed 7 5
Median (Full Range)
Unit of Measure: units on a scale
-3
(-13.5 to 0)
0
(-6 to 1.5)
2.Secondary Outcome
Title Change in Hamilton Rating Scale for Depression - 6 Items (HAM-D-6), Day 20
Hide Description

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.

Time Frame Baseline and 20 days after initiating treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:
either dose (10 mg/day or 20 mg/day) of CERC-501 in drug-drug arms
Placebo therapy in placebo-placebo arm
Overall Number of Participants Analyzed 3 1
Median (Full Range)
Unit of Measure: units on a scale
-3.5
(-5.5 to -0.5)
-3.5
(-3.5 to -3.5)
3.Secondary Outcome
Title Number of Participants With Response on Hamilton Rating Scale for Depression - 6 Items (HAM-D-6)
Hide Description

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.

Time Frame 72 hours after treatment initiation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

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.

Overall Number of Participants Analyzed 7 5
Measure Type: Count of Participants
Unit of Measure: Participants
2
  28.6%
1
  20.0%
4.Secondary Outcome
Title Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Hide Description

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.

Time Frame Baseline and 72 hours and 20 days after initiating treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

For time frame through 72 hours: either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

For 20-day time frame: either dose drug-drug arms only

For time frame through 72 hours: 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.

For 20-day time frame: placebo-placebo arm only

Overall Number of Participants Analyzed 7 5
Median (Full Range)
Unit of Measure: units on a scale
72-hour change Number Analyzed 7 participants 5 participants
-6.5
(-33 to 0)
-4.5
(-17 to 3)
20-day change Number Analyzed 3 participants 1 participants
-8
(-15.5 to -4.5)
-9
(-9 to -9)
5.Secondary Outcome
Title Change in Clinical Global Impression -Severity (CGI-S)
Hide Description

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.

Time Frame Baseline and 72 hours and 20 days after initiating treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

For time frame through 72 hours: either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

For 20-day time frame: either dose drug-drug arms only

For time frame through 72 hours: 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.

For 20-day time frame: placebo-placebo arm only

Overall Number of Participants Analyzed 7 5
Median (Full Range)
Unit of Measure: units on a scale
72-hour change Number Analyzed 7 participants 5 participants
-0.5
(-4 to 0)
0
(-3 to 0.5)
20-day change Number Analyzed 3 participants 1 participants
-1
(-1.5 to 0)
-1
(-1 to -1)
6.Secondary Outcome
Title Clinical Global Impression-Improvement (CGI-I)
Hide Description 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.
Time Frame 72 hours and 20 days after initiating treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

For time frame through 72 hours: either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

For 20-day time frame: either dose drug-drug arms only

For time frame through 72 hours: 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.

For 20-day time frame: placebo-placebo arm only

Overall Number of Participants Analyzed 7 5
Median (Full Range)
Unit of Measure: units on a scale
72 hours Number Analyzed 7 participants 5 participants
3
(1 to 4)
4
(2 to 4)
20 days Number Analyzed 3 participants 1 participants
3
(3 to 4)
4
(4 to 4)
7.Secondary Outcome
Title Change in Symptoms of Depression Questionnaire (SDQ)
Hide Description

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.

Time Frame Baseline and 72 hours and 20 days after initiating treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

For time frame through 72 hours: either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

For 20-day time frame: either dose drug-drug arms only

For time frame through 72 hours: 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.

For 20-day time frame: placebo-placebo arm only

Overall Number of Participants Analyzed 7 5
Median (Full Range)
Unit of Measure: units on a scale
72-hour change Number Analyzed 7 participants 5 participants
-26
(-69.5 to 0)
-7.5
(-48 to 5)
20-day change Number Analyzed 3 participants 1 participants
-15.5
(-38.5 to -8.5)
-3.5
(-3.5 to -3.5)
8.Secondary Outcome
Title Change in Perceived Stress Scale (PSS)
Hide Description

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.

Time Frame Baseline and 72 hours and 20 days after treatment initiation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

For time frame through 72 hours: either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

For 20-day time frame: either dose drug-drug arms only

For time frame through 72 hours: 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.

For 20-day time frame: placebo-placebo arm only

Overall Number of Participants Analyzed 6 4
Median (Full Range)
Unit of Measure: units on a scale
72-hour change Number Analyzed 6 participants 4 participants
-3.5
(-13 to -1)
-1.25
(-2 to 2.5)
20-day change Number Analyzed 2 participants 1 participants
-7.25
(-12 to -2.5)
0.5
(0.5 to 0.5)
9.Secondary Outcome
Title Change in Positive Affect Scale (PAS)
Hide Description

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.

Time Frame Baseline and 72 hours and 20 days after initiating treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

For time frame through 72 hours: either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

For 20-day time frame: either dose drug-drug arms only

For time frame through 72 hours: 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.

For 20-day time frame: placebo-placebo arm only

Overall Number of Participants Analyzed 6 5
Median (Full Range)
Unit of Measure: units on a scale
72-hour change Number Analyzed 6 participants 5 participants
8
(-5.5 to 19)
17.5
(-25.5 to 31)
20-day change Number Analyzed 3 participants 1 participants
11
(5 to 16.5)
0
(0 to 0)
10.Secondary Outcome
Title Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Satisfaction With Participation in Social Roles and Discretionary Activities
Hide Description

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.

Time Frame Baseline and 72 hours and 20 days after initiating treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

For time frame through 72 hours: either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

For 20-day time frame: either dose drug-drug arms only

For time frame through 72 hours: 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.

For 20-day time frame: placebo-placebo arm only

Overall Number of Participants Analyzed 7 5
Median (Full Range)
Unit of Measure: units on a scale
Social Roles 72-hour change Number Analyzed 7 participants 5 participants
2.5
(-4 to 11.5)
1.5
(-4 to 11)
Social Roles 20-day change Number Analyzed 3 participants 1 participants
-1.5
(-3 to 7)
3
(3 to 3)
Discretionary Activities 72-hour change Number Analyzed 7 participants 5 participants
3
(0 to 16)
1.5
(-2.5 to 6)
Discretionary Activities 20-day change Number Analyzed 3 participants 1 participants
4
(-1 to 7.5)
5
(5 to 5)
11.Secondary Outcome
Title Change in the Columbia-Suicide Severity Rating Scale (C-SSRS)
Hide Description 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).
Time Frame Baseline and 72 hours after initiating treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

For time frame through 72 hours: either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

For time frame through 72 hours: 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.

Overall Number of Participants Analyzed 6 2
Median (Full Range)
Unit of Measure: units on a scale
Suicidal Ideation
0
(-2 to 0)
0
(0 to 0)
Suicidal Behavior
0
(0 to 0)
0
(0 to 0)
12.Secondary Outcome
Title Number of Participants With Clinically Significant Abnormal ECG
Hide Description Number of Participants with clinically significant abnormal electrocardiogram (ECG)
Time Frame 72 hours after treatment initiation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

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.

Overall Number of Participants Analyzed 7 5
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
13.Secondary Outcome
Title Number of Participants With Clinically Significant Abnormal Labs
Hide Description Total number of participants with clinically significant abnormal labs
Time Frame 72 hours after treatment initiation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CERC-501 Placebo
Hide Arm/Group Description:

either dose (10 mg/day or 20 mg/day) of CERC-501; pooled patients from phase 1 and those on drug 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.

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.

Overall Number of Participants Analyzed 7 5
Measure Type: Count of Participants
Unit of Measure: Participants
Total RBC
1
  14.3%
1
  20.0%
Hematocrit
1
  14.3%
1
  20.0%
Any lab
1
  14.3%
1
  20.0%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Low Dose Drug High Dose Drug Placebo
Hide Arm/Group Description Patients receive CERC-501 10.0 mg/day Patients receive CERC-501 20.0 mg/day Patients receive placebo
All-Cause Mortality
Low Dose Drug High Dose Drug Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Low Dose Drug High Dose Drug Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/4 (0.00%)      0/4 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Low Dose Drug High Dose Drug Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/3 (66.67%)      2/4 (50.00%)      2/4 (50.00%)    
Gastrointestinal disorders       
Gastrointestinal disturbance  1/3 (33.33%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
General disorders       
Fatigue  1/3 (33.33%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Remembered dreams (unusual for subject)  0/3 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Nervous system disorders       
Central Nervous Systems Lesions  0/3 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Psychiatric disorders       
Insomnia  0/3 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0
Worsening depression  1/3 (33.33%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Renal and urinary disorders       
Renal colic  0/3 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  2
Microscopic hematuria (grade 1)  0/3 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Renal calculi (Grade 2)  0/3 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Respiratory, thoracic and mediastinal disorders       
Nasal congestion  1/3 (33.33%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Rhinorrhea  1/3 (33.33%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Upper respiratory infection  0/3 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Skin and subcutaneous tissue disorders       
Acne  1/3 (33.33%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
itching on thighs  0/3 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Maurizio Fava, MD
Organization: Massachusetts General Hospital
Phone: 617-724-2513
Responsible Party: Maurizio Fava, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01913535     History of Changes
Other Study ID Numbers: RAP-002
271201100006I-0-27100007-1 ( U.S. NIH Grant/Contract )
First Submitted: July 30, 2013
First Posted: August 1, 2013
Results First Submitted: April 17, 2017
Results First Posted: July 2, 2017
Last Update Posted: July 2, 2017