Trial Outcomes & Findings for A Study of Rapastinel for Rapid Treatment of Depression and Suicidality in Major Depressive Disorder (NCT NCT03352453)

Last Updated: 2020-08-14

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 a 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

TERMINATED

Study phase

PHASE2

Target enrollment

138 participants

Primary outcome timeframe

Baseline and 1 Day

Results posted on

2020-08-14

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo-matching rapastinel weekly IV injections.	Rapastinel 450mg Rapastinel 450 milligram (mg) weekly intravenous (IV) injections.
Overall Study STARTED	66	72
Overall Study COMPLETED	44	40
Overall Study NOT COMPLETED	22	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo-matching rapastinel weekly IV injections.	Rapastinel 450mg Rapastinel 450 milligram (mg) weekly intravenous (IV) injections.
Overall Study Miscellaneous Reasons	1	2
Overall Study Lack of Efficacy	1	0
Overall Study Withdrawal by Subject	8	14
Overall Study Study Terminated by Sponsor	2	1
Overall Study Protocol Deviation	1	0
Overall Study Lost to Follow-up	7	6
Overall Study Adverse Event	2	9

Baseline Characteristics

A Study of Rapastinel for Rapid Treatment of Depression and Suicidality in Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=64 Participants Placebo-matching rapastinel weekly IV injections.	Rapastinel 450mg n=72 Participants Rapastinel 450 milligram (mg) weekly intravenous (IV) injections.	Total n=136 Participants Total of all reporting groups
Age, Continuous	42.1 Years STANDARD_DEVIATION 13.45 • n=5 Participants	42.3 Years STANDARD_DEVIATION 12.89 • n=7 Participants	42.2 Years STANDARD_DEVIATION 13.11 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	29 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	43 Participants n=7 Participants	78 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	55 Participants n=5 Participants	61 Participants n=7 Participants	116 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 (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	33 Participants n=5 Participants	24 Participants n=7 Participants	57 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	45 Participants n=7 Participants	75 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Montgomery-Asberg Depression Rating Scale (MADRS) total score at baseline	40.4 Scores on a scale STANDARD_DEVIATION 5.83 • n=5 Participants	39.8 Scores on a scale STANDARD_DEVIATION 6.04 • n=7 Participants	40.0 Scores on a scale STANDARD_DEVIATION 5.93 • n=5 Participants
Sheehan - Suicidality Tracking Scale (S-STS) Total Score (Patient-rated)	30.9 Scores on a scale STANDARD_DEVIATION 10.94 • n=5 Participants	29.6 Scores on a scale STANDARD_DEVIATION 10.45 • n=7 Participants	30.2 Scores on a scale STANDARD_DEVIATION 10.67 • n=5 Participants
Weight	85.26 kg STANDARD_DEVIATION 19.80 • n=5 Participants	82.57 kg STANDARD_DEVIATION 17.59 • n=7 Participants	83.83 kg STANDARD_DEVIATION 18.64 • n=5 Participants
Height	172 cm STANDARD_DEVIATION 8.84 • n=5 Participants	169.56 cm STANDARD_DEVIATION 9.86 • n=7 Participants	170.71 cm STANDARD_DEVIATION 9.44 • n=5 Participants
BMI	28.88 kg/m^2 STANDARD_DEVIATION 6.75 • n=5 Participants	28.79 kg/m^2 STANDARD_DEVIATION 6.34 • n=7 Participants	28.83 kg/m^2 STANDARD_DEVIATION 6.51 • n=5 Participants
S-STS Total Score (Clinician-rated)	30.0 Scores on a scale STANDARD_DEVIATION 10.22 • n=5 Participants	28.9 Scores on a scale STANDARD_DEVIATION 9.62 • n=7 Participants	29.4 Scores on a scale STANDARD_DEVIATION 9.88 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 1 Day

Population: The modified Intent-to-Treat (mITT) Population consists of all participants in the Safety Population who had at least 1 postbaseline assessment of the MADRS total score or S-STS total score.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Placebo-matching rapastinel weekly IV injections.	Rapastinel 450mg n=72 Participants Rapastinel 450 milligram (mg) weekly intravenous (IV) injections.
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	-17.6 Scores on a scale Standard Deviation 12.49	-16.3 Scores on a scale Standard Deviation 11.36

PRIMARY outcome

Timeframe: Baseline and 1 Day

Population: The modified Intent-to-Treat (mITT) Population consists of all patients in the Safety Population who had at least 1 postbaseline assessment of the MADRS total score or S-STS total score.

The S-STS is a patient-report informed, clinician-rated scale used to rate the severity of suicidal impulses, thoughts, and behaviors. This is a 14 item scale ranging from 0=Not at all to 4= Extremely. The total score ranges from 0 to 56 with a higher score indicating higher suicidal tendency.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Placebo-matching rapastinel weekly IV injections.	Rapastinel 450mg n=72 Participants Rapastinel 450 milligram (mg) weekly intravenous (IV) injections.
Change From Baseline in Sheehan - Suicidality Tracking Scale (S-STS) Total Score	-20.6 Scores on a scale Standard Deviation 12.27	-20.2 Scores on a scale Standard Deviation 11.93

SECONDARY outcome

Timeframe: Baseline and 28 Days

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Placebo-matching rapastinel weekly IV injections.	Rapastinel 450mg n=72 Participants Rapastinel 450 milligram (mg) weekly intravenous (IV) injections.
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	-25.6 Scores on a scale Standard Deviation 14.74	-23.0 Scores on a scale Standard Deviation 15.00

SECONDARY outcome

Timeframe: Baseline and 28 Days

Population: The modified Intent-to-Treat (mITT) Population consists of all patients in the Safety Population who had at least 1 postbaseline assessment of the MADRS total score or S-STS total score.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Placebo-matching rapastinel weekly IV injections.	Rapastinel 450mg n=72 Participants Rapastinel 450 milligram (mg) weekly intravenous (IV) injections.
Change From Baseline in Sheehan - Suicidality Tracking Scale (S-STS) Total Score	-25.9 Scores on a scale Standard Deviation 11.61	-26.4 Scores on a scale Standard Deviation 12.74

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

Rapastinel 450mg

Serious events: 12 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=64 participants at risk Placebo-matching rapastinel weekly IV injections.	Rapastinel 450mg n=72 participants at risk Rapastinel 450 milligram (mg) weekly intravenous (IV) injections.
Psychiatric disorders Suicidal ideation	4.7% 3/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	6.9% 5/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
General disorders Non-cardiac chest pain	1.6% 1/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	1.4% 1/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Psychiatric disorders Anxiety	1.6% 1/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	1.4% 1/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Psychiatric disorders Depressive Symptom	1.6% 1/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	1.4% 1/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Psychiatric disorders Suicide attempt	0.00% 0/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	4.2% 3/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Psychiatric disorders Major Depression	0.00% 0/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	1.4% 1/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Psychiatric disorders Depression	0.00% 0/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	1.4% 1/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Infections and infestations Diverticulitis	0.00% 0/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	1.4% 1/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	1.4% 1/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Cardiac disorders Mitral Valve Incompetence	0.00% 0/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	1.4% 1/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Cardiac disorders Mitral Valve Prolapse	0.00% 0/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	1.4% 1/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Renal and urinary disorders Nephrolithiasis	0.00% 0/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	1.4% 1/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.

Other adverse events

Other adverse events
Measure	Placebo n=64 participants at risk Placebo-matching rapastinel weekly IV injections.	Rapastinel 450mg n=72 participants at risk Rapastinel 450 milligram (mg) weekly intravenous (IV) injections.
Psychiatric disorders Anxiety	7.8% 5/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	6.9% 5/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Nervous system disorders Headache	7.8% 5/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	8.3% 6/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Psychiatric disorders Insomnia	4.7% 3/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	8.3% 6/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Nervous system disorders Dizziness	4.7% 3/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	6.9% 5/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.
Gastrointestinal disorders Nausea	7.8% 5/64 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.	5.6% 4/72 • The study consisted of a 4 week double-blind treatment period, followed by a 1-week safety follow-up period. The Safety Population will consist of all patients in the Randomized Population who took at least 1 dose of randomized IP.

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