Trial Outcomes & Findings for Study of Rapastinel as Monotherapy in Patients With MDD (NCT NCT03560518)

Last Updated: 2020-09-01

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

PHASE3

Target enrollment

439 participants

Primary outcome timeframe

Baseline to end of Week 6

Results posted on

2020-09-01

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo (prefilled syringe, weekly IV administration)	Rapastinel 450mg Rapastinel 450 mg (prefilled syringe, weekly intravenous IV administration)	Rapastinel 900mg Rapastinel 900 mg (prefilled syringe, weekly intravenous IV administration)
Double Blind Treatment Period STARTED	147	145	147
Double Blind Treatment Period COMPLETED	122	116	124
Double Blind Treatment Period NOT COMPLETED	25	29	23
Safety Follow-Up Period STARTED	10	17	22
Safety Follow-Up Period COMPLETED	10	17	22
Safety Follow-Up Period NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo (prefilled syringe, weekly IV administration)	Rapastinel 450mg Rapastinel 450 mg (prefilled syringe, weekly intravenous IV administration)	Rapastinel 900mg Rapastinel 900 mg (prefilled syringe, weekly intravenous IV administration)
Double Blind Treatment Period Miscellaneous Reasons	1	0	0
Double Blind Treatment Period Study Terminated by the Sponsor	6	9	10
Double Blind Treatment Period Protocol Violation	1	2	0
Double Blind Treatment Period Pregnancy	0	2	0
Double Blind Treatment Period Lost to Follow-up	5	6	6
Double Blind Treatment Period Withdrawal by Subject	10	6	5
Double Blind Treatment Period Lack of Efficacy	2	1	1
Double Blind Treatment Period Adverse Event	0	3	1

Baseline Characteristics

Study of Rapastinel as Monotherapy in Patients With MDD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=146 Participants Placebo (prefilled syringe, weekly IV administration)	Rapastinel 450mg n=144 Participants Rapastinel 450 mg (prefilled syringe, weekly intravenous IV administration)	Rapastinel 900mg n=147 Participants Rapastinel 900 mg (prefilled syringe, weekly intravenous IV administration)	Total n=437 Participants Total of all reporting groups
Age, Continuous	43.9 Years STANDARD_DEVIATION 14.35 • n=5 Participants	45.8 Years STANDARD_DEVIATION 14.02 • n=7 Participants	44.5 Years STANDARD_DEVIATION 13.14 • n=5 Participants	44.7 Years STANDARD_DEVIATION 13.84 • n=4 Participants
Sex: Female, Male Female	98 Participants n=5 Participants	100 Participants n=7 Participants	101 Participants n=5 Participants	299 Participants n=4 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	44 Participants n=7 Participants	46 Participants n=5 Participants	138 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants	30 Participants n=7 Participants	21 Participants n=5 Participants	76 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=5 Participants	114 Participants n=7 Participants	126 Participants n=5 Participants	361 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Black or African American	31 Participants n=5 Participants	27 Participants n=7 Participants	35 Participants n=5 Participants	93 Participants n=4 Participants
Race (NIH/OMB) White	106 Participants n=5 Participants	111 Participants n=7 Participants	103 Participants n=5 Participants	320 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Weight	86.42 kg STANDARD_DEVIATION 18.11 • n=5 Participants	88.20 kg STANDARD_DEVIATION 18.61 • n=7 Participants	85.33 kg STANDARD_DEVIATION 20.71 • n=5 Participants	86.64 kg STANDARD_DEVIATION 19.18 • n=4 Participants
Height	168.41 cm STANDARD_DEVIATION 9.66 • n=5 Participants	168.75 cm STANDARD_DEVIATION 9.83 • n=7 Participants	168.57 cm STANDARD_DEVIATION 10.21 • n=5 Participants	168.58 cm STANDARD_DEVIATION 9.88 • n=4 Participants
BMI	30.54 kg/m^2 STANDARD_DEVIATION 6.39 • n=5 Participants	30.96 kg/m^2 STANDARD_DEVIATION 6.13 • n=7 Participants	30.00 kg/m^2 STANDARD_DEVIATION 6.96 • n=5 Participants	30.50 kg/m^2 STANDARD_DEVIATION 6.50 • n=4 Participants
Montgomery-Asberg Depression Rating Scale (MADRS) total score at baseline	35.4 Score on a Scale STANDARD_DEVIATION 4.50 • n=5 Participants	35.1 Score on a Scale STANDARD_DEVIATION 4.71 • n=7 Participants	35.9 Score on a Scale STANDARD_DEVIATION 4.69 • n=5 Participants	35.5 Score on a Scale STANDARD_DEVIATION 4.63 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline to end of Week 6

Population: The modified Intent-to-Treat (mITT) Population will consist 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=146 Participants Placebo (prefilled syringe, weekly IV administration)	Rapastinel 450mg n=144 Participants Rapastinel 450 mg (prefilled syringe, weekly intravenous IV administration)	Rapastinel 900mg n=147 Participants Rapastinel 900 mg (prefilled syringe, weekly intravenous IV administration)
Change From Baseline on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at End of Treatment (End of Week 6)	-13.8 Scores on a scale Standard Deviation 11.93	-13.2 Scores on a scale Standard Deviation 11.62	-11.3 Scores on a scale Standard Deviation 11.36

SECONDARY outcome

Timeframe: Baseline to Day 1 post-first dose

Outcome measures

Outcome measures
Measure	Placebo n=146 Participants Placebo (prefilled syringe, weekly IV administration)	Rapastinel 450mg n=144 Participants Rapastinel 450 mg (prefilled syringe, weekly intravenous IV administration)	Rapastinel 900mg n=147 Participants Rapastinel 900 mg (prefilled syringe, weekly intravenous IV administration)
Change From Baseline in MADRS Total Score at Day 1 Post-first Dose of Treatment	-11.0 Scores on a Scale Standard Deviation 9.47	-9.0 Scores on a Scale Standard Deviation 9.18	-8.3 Scores on a Scale Standard Deviation 8.36

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Rapastinel 450mg

Serious events: 2 serious events

Other events: 28 other events

Deaths: 1 deaths

Rapastinel 900mg

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=147 participants at risk Placebo (prefilled syringe, weekly IV administration)	Rapastinel 450mg n=145 participants at risk Rapastinel 450 mg (prefilled syringe, weekly intravenous IV administration)	Rapastinel 900mg n=147 participants at risk Rapastinel 900 mg (prefilled syringe, weekly intravenous IV administration)
Blood and lymphatic system disorders Anaemia	0.68% 1/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	0.00% 0/145 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	0.00% 0/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.
Surgical and medical procedures Abortion induced	0.00% 0/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	0.69% 1/145 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	0.00% 0/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.
Respiratory, thoracic and mediastinal disorders Asphyxia	0.00% 0/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	0.69% 1/145 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	0.00% 0/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.
Psychiatric disorders Depression	0.00% 0/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	0.00% 0/145 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	0.68% 1/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.68% 1/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	0.00% 0/145 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	0.00% 0/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.

Other adverse events

Other adverse events
Measure	Placebo n=147 participants at risk Placebo (prefilled syringe, weekly IV administration)	Rapastinel 450mg n=145 participants at risk Rapastinel 450 mg (prefilled syringe, weekly intravenous IV administration)	Rapastinel 900mg n=147 participants at risk Rapastinel 900 mg (prefilled syringe, weekly intravenous IV administration)
Nervous system disorders Headache	7.5% 11/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	9.0% 13/145 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	7.5% 11/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.
Infections and infestations Nasopharyngitis	4.1% 6/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	6.2% 9/145 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	5.4% 8/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.
Nervous system disorders Dysgeusia	0.00% 0/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	7.6% 11/145 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received at least 1 dose of randomized IP.	2.7% 4/147 • The study consisted of a 6 week double-blind treatment period, followed by a 2-week safety follow-up period. The Safety Population consists of all randomized patients who received 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