Trial Outcomes & Findings for A Study of Rapastinel as Adjunctive Therapy in Major Depressive Disorder (RAP-MD-03) (NCT NCT02943577)

Last Updated: 2019-11-13

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

429 participants

Primary outcome timeframe

Baseline and 3 Weeks

Results posted on

2019-11-13

Participant Flow

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

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 450 mg Rapastinel 450 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.
Overall Study STARTED	209	206
Overall Study COMPLETED	204	201
Overall Study NOT COMPLETED	5	5

Reasons for withdrawal

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 450 mg Rapastinel 450 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.
Overall Study Protocol Violation	0	1
Overall Study Adverse Event	3	2
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	1	1
Overall Study Pregnancy	1	0

Baseline Characteristics

A Study of Rapastinel as Adjunctive Therapy in Major Depressive Disorder (RAP-MD-03)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=209 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 450 mg n=206 Participants Rapastinel 450 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.	Total n=415 Participants Total of all reporting groups
Age, Continuous	46.4 Years STANDARD_DEVIATION 11.93 • n=5 Participants	47.4 Years STANDARD_DEVIATION 11.34 • n=7 Participants	46.9 Years STANDARD_DEVIATION 11.64 • n=5 Participants
Sex: Female, Male Female	151 Participants n=5 Participants	156 Participants n=7 Participants	307 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	50 Participants n=7 Participants	108 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants	34 Participants n=7 Participants	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	184 Participants n=5 Participants	172 Participants n=7 Participants	356 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	156 Participants n=5 Participants	157 Participants n=7 Participants	313 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	48 Participants n=5 Participants	45 Participants n=7 Participants	93 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
MADRS total score at baseline	33.8 Scores on a Scale STANDARD_DEVIATION 4.83 • n=5 Participants	34.1 Scores on a Scale STANDARD_DEVIATION 4.73 • n=7 Participants	34.0 Scores on a Scale STANDARD_DEVIATION 4.76 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 3 Weeks

Population: 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

Outcome measures

Outcome measures
Measure	Placebo n=209 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 450 mg n=206 Participants Rapastinel 450 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.
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at the End of Study	-4.1 Score on a Scale Standard Error 0.64	-5.1 Score on a Scale Standard Error 0.66

SECONDARY outcome

Timeframe: Baseline and Day 8

Outcome measures

Outcome measures
Measure	Placebo n=209 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 450 mg n=206 Participants Rapastinel 450 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.
Change From Baseline in MADRS Total Score	-4.3 Score on a Scale Standard Error 0.53	-3.9 Score on a Scale Standard Error 0.55

SECONDARY outcome

Timeframe: Baseline and Day 21

Population: The baseline population for placebo non-responders is 284.

Outcome measures

Outcome measures
Measure	Placebo n=145 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 450 mg n=139 Participants Rapastinel 450 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.
Change From Baseline to Day 21 in MADRS Total Score for the Placebo Non-responders of mITT Population	-4.6 Score on a Scale Standard Error 0.72	-4.6 Score on a Scale Standard Error 0.74

SECONDARY outcome

Timeframe: Baseline and Day 8

Population: The baseline population for placebo non-responders is 284.

Outcome measures

Outcome measures
Measure	Placebo n=145 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 450 mg n=139 Participants Rapastinel 450 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.
Change From Baseline to Day 8 in MADRS Total Score for the Placebo Non-responders of mITT Population	-4.1 Score on a Scale Standard Error 0.61	-3.6 Score on a Scale Standard Error 0.62

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 18 other events

Deaths: 1 deaths

Rapastinel 450 mg

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=209 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 450 mg n=206 participants at risk Rapastinel 450 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.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.66% 1/151 • 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% 0/156 • 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.
Respiratory, thoracic and mediastinal disorders Asthma	0.48% 1/209 • 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% 0/206 • 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.
Nervous system disorders Subarachnoid haemorrhage	0.48% 1/209 • 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% 0/206 • 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

Other adverse events
Measure	Placebo n=209 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 450 mg n=206 participants at risk Rapastinel 450 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.
Nervous system disorders Headache	8.6% 18/209 • 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.	7.3% 15/206 • 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

Therapeutic Area, Head

Allergan

Phone: 714-246-4500

Email: [email protected]

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