Trial Outcomes & Findings for A Study of Rapastinel as Adjunctive Therapy in Major Depressive Disorder (RAP-MD-02) (NCT NCT02943564)
NCT ID: NCT02943564
Last Updated: 2019-12-27
Results Overview
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
658 participants
Primary outcome timeframe
Baseline and 3 Weeks
Results posted on
2019-12-27
Participant Flow
658 total enrolled. 20 discontinued prior to randomization.
Prior to randomization, patients entered a 1-wk, double-blind, placebo lead-in period to identify placebo responders. Upon completion of the placebo lead-in period, patients were randomized in 1:1 ratio to receive either rapastinel or placebo. Randomization was stratified by patient's responder status (placebo non-responder vs. placebo responder).
Participant milestones
| Measure |
Placebo
Placebo-matching rapastinel weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 225 mg
Rapastinel 225 milligram (mg) weekly intravenous (IV) injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 450 mg
Rapastinel 450 mg weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
|---|---|---|---|
|
Overall Study
STARTED
|
217
|
211
|
210
|
|
Overall Study
Responder
|
83
|
77
|
77
|
|
Overall Study
Non-Responder
|
134
|
134
|
133
|
|
Overall Study
COMPLETED
|
207
|
198
|
201
|
|
Overall Study
NOT COMPLETED
|
10
|
13
|
9
|
Reasons for withdrawal
| Measure |
Placebo
Placebo-matching rapastinel weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 225 mg
Rapastinel 225 milligram (mg) weekly intravenous (IV) injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 450 mg
Rapastinel 450 mg weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
|---|---|---|---|
|
Overall Study
Miscellaneous Reasons
|
0
|
0
|
3
|
|
Overall Study
Site terminated by sponsor
|
0
|
1
|
0
|
|
Overall Study
Non-compliance with study drug
|
0
|
1
|
0
|
|
Overall Study
Pregnancy
|
0
|
1
|
1
|
|
Overall Study
Protocol Violation
|
2
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
6
|
5
|
2
|
|
Overall Study
Adverse Event
|
1
|
2
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
0
|
Baseline Characteristics
A Study of Rapastinel as Adjunctive Therapy in Major Depressive Disorder (RAP-MD-02)
Baseline characteristics by cohort
| Measure |
Placebo
n=217 Participants
Placebo-matching rapastinel weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 225 mg
n=211 Participants
Rapastinel 225 milligram (mg) weekly intravenous (IV) injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 450 mg
n=210 Participants
Rapastinel 450 mg weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Total
n=638 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
44.1 Years
STANDARD_DEVIATION 11.75 • n=93 Participants
|
44.3 Years
STANDARD_DEVIATION 13.16 • n=4 Participants
|
44.7 Years
STANDARD_DEVIATION 12.27 • n=27 Participants
|
44.3 Years
STANDARD_DEVIATION 12.38 • n=483 Participants
|
|
Sex: Female, Male
Female
|
141 Participants
n=93 Participants
|
147 Participants
n=4 Participants
|
153 Participants
n=27 Participants
|
441 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
76 Participants
n=93 Participants
|
64 Participants
n=4 Participants
|
57 Participants
n=27 Participants
|
197 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
25 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
73 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
192 Participants
n=93 Participants
|
189 Participants
n=4 Participants
|
184 Participants
n=27 Participants
|
565 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
White
|
170 Participants
n=93 Participants
|
162 Participants
n=4 Participants
|
159 Participants
n=27 Participants
|
491 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
41 Participants
n=93 Participants
|
46 Participants
n=4 Participants
|
42 Participants
n=27 Participants
|
129 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
MADRS total score at baseline
|
33.6 Scores on a Scale
STANDARD_DEVIATION 4.47 • n=93 Participants
|
33.5 Scores on a Scale
STANDARD_DEVIATION 4.67 • n=4 Participants
|
33.5 Scores on a Scale
STANDARD_DEVIATION 4.85 • n=27 Participants
|
33.6 Scores on a Scale
STANDARD_DEVIATION 4.70 • n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline and 3 WeeksPopulation: The modified Intent-to-Treat (mITT) Population will consist of all patients who were randomized, received at least 1 dose of IP during the randomized treatment period, and had at least 1 post-randomization assessment of the MADRS total score
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.
Outcome measures
| Measure |
Placebo
n=217 Participants
Placebo-matching rapastinel weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 225 mg
n=211 Participants
Rapastinel 225 milligram (mg) weekly intravenous (IV) injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 450 mg
n=210 Participants
Rapastinel 450 mg weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
|---|---|---|---|
|
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at the End of Study
|
-4.9 Score on a Scale
Standard Error 0.59
|
-4.8 Score on a Scale
Standard Error 0.60
|
-5.4 Score on a Scale
Standard Error 0.60
|
SECONDARY outcome
Timeframe: Baseline and Day 8Population: The modified Intent-to-Treat (mITT) Population will consist of all patients who were randomized, received at least 1 dose of IP during the randomized treatment period, and had at least 1 post-randomization assessment of the MADRS total score
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.
Outcome measures
| Measure |
Placebo
n=217 Participants
Placebo-matching rapastinel weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 225 mg
n=211 Participants
Rapastinel 225 milligram (mg) weekly intravenous (IV) injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 450 mg
n=210 Participants
Rapastinel 450 mg weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
|---|---|---|---|
|
Change From Baseline in MADRS Total Score
|
-4.5 Score on a Scale
Standard Error 0.51
|
-4.6 Score on a Scale
Standard Error 0.52
|
-4.5 Score on a Scale
Standard Error 0.52
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths
Rapastinel 225 mg
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Rapastinel 450 mg
Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=217 participants at risk
Placebo-matching rapastinel weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 225 mg
n=211 participants at risk
Rapastinel 225 milligram (mg) weekly intravenous (IV) injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 450 mg
n=210 participants at risk
Rapastinel 450 mg weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.46%
1/217 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.00%
0/211 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.00%
0/210 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.46%
1/217 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.00%
0/211 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.00%
0/210 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.46%
1/217 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.00%
0/211 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.00%
0/210 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/217 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.47%
1/211 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.00%
0/210 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
0.00%
0/217 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.00%
0/211 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.48%
1/210 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.00%
0/217 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.47%
1/211 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
0.00%
0/210 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
Other adverse events
| Measure |
Placebo
n=217 participants at risk
Placebo-matching rapastinel weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 225 mg
n=211 participants at risk
Rapastinel 225 milligram (mg) weekly intravenous (IV) injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
Rapastinel 450 mg
n=210 participants at risk
Rapastinel 450 mg weekly IV injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
6.5%
14/217 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
5.2%
11/211 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
6.7%
14/210 • Adverse Events were collected for up to 28 days.
The Safety Population will consist of all patients who were randomized and received at least 1 dose of IP during the randomized treatment period.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER