Trial Outcomes & Findings for Long-term Safety Study of Rapastinel as Adjunctive Therapy in Patients With Major Depressive Disorder (NCT NCT03002077)
NCT ID: NCT03002077
Last Updated: 2020-06-22
Results Overview
An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
617 participants
Primary outcome timeframe
52 Weeks
Results posted on
2020-06-22
Participant Flow
The study was planned to be terminated when 100 patients had completed the 52-week Open Label Treatment Period (OLTP).
Patients who either completed the RAP-MD-04 Double-blind Treatment Period (DBTP) or who did not meet criteria to be randomized into the DBTP of RAP-MD-04 and were therefore discontinued from that study were eligible for Study RAP-MD-06.
Participant milestones
| Measure |
Rapastinel
Rapastinel 450 milligrams (mg) intravenous (IV) open label weekly or every two weeks, based on investigator's discretion for 52 Weeks.
|
|---|---|
|
Overall Study
STARTED
|
617
|
|
Overall Study
COMPLETED
|
179
|
|
Overall Study
NOT COMPLETED
|
438
|
Reasons for withdrawal
| Measure |
Rapastinel
Rapastinel 450 milligrams (mg) intravenous (IV) open label weekly or every two weeks, based on investigator's discretion for 52 Weeks.
|
|---|---|
|
Overall Study
Non-compliance with Study Drug
|
4
|
|
Overall Study
Non-compliance w/Background ADT
|
1
|
|
Overall Study
Study Terminated by Sponsor
|
257
|
|
Overall Study
Site Terminated by Sponsor
|
5
|
|
Overall Study
Miscellaneous Reasons
|
10
|
|
Overall Study
Adverse Event
|
23
|
|
Overall Study
Lack of Efficacy
|
20
|
|
Overall Study
Withdrawal by Subject
|
72
|
|
Overall Study
Lost to Follow-up
|
21
|
|
Overall Study
Pregnancy
|
4
|
|
Overall Study
Protocol Violation
|
21
|
Baseline Characteristics
Long-term Safety Study of Rapastinel as Adjunctive Therapy in Patients With Major Depressive Disorder
Baseline characteristics by cohort
| Measure |
Rapastinel
n=617 Participants
Rapastinel 450 milligrams (mg) intravenous (IV) open label weekly or every two weeks, based on investigator's discretion for 52 Weeks.
|
|---|---|
|
Age, Continuous
|
46.5 Years
STANDARD_DEVIATION 11.86 • n=5 Participants
|
|
Sex: Female, Male
Female
|
455 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
162 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
83 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
534 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
485 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
107 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 52 WeeksPopulation: The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Outcome measures
| Measure |
Rapastinel
n=617 Participants
Rapastinel 450 milligrams (mg) intravenous (IV) open label weekly or every two weeks, based on investigator's discretion for 52 Weeks.
|
|---|---|
|
The Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
457 Count of Participants
|
SECONDARY outcome
Timeframe: Baseline to 52 WeeksPopulation: The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
The BPRS+ is a subset of the BPRS that assesses 4 components of the BPRS+ related to the degree of psychosis: Conceptual Disorganization, Suspiciousness, Hallucinatory Behavior, and Unusual Thought Content assessed by the investigator using a 7-point scale ranging from 1=Not Present to 7=Extremely Severe for a total possible score of 0 (best) to 28 (worst). A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Rapastinel
n=617 Participants
Rapastinel 450 milligrams (mg) intravenous (IV) open label weekly or every two weeks, based on investigator's discretion for 52 Weeks.
|
|---|---|
|
Change From Baseline in Brief Psychiatric Rating Scale Positive Symptoms Subscale (BPRS+)
|
-0.0 Scores on a scale
Standard Deviation 0.33
|
SECONDARY outcome
Timeframe: Baseline to 52 WeeksPopulation: The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
The Clinician Administered Dissociative States Scale (CADSS) is a clinician-administered measure of perceptual, behavioral, and attentional alterations occurring during active dissociative experiences composed of 23 subjective self-reported and 5 objective observer-reported ratings, each scored from 0 (not at all) to 4 (extremely). Only the 23 subjective items will be collected and analyzed. The sum of each of the 23 subjective items was used for a total score of 0-92. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Rapastinel
n=617 Participants
Rapastinel 450 milligrams (mg) intravenous (IV) open label weekly or every two weeks, based on investigator's discretion for 52 Weeks.
|
|---|---|
|
Change From Baseline in the Clinician Administered Dissociative States Scale (CADSS)
|
-0.2 Scores on a Scale
Standard Deviation 1.24
|
Adverse Events
Rapastinel
Serious events: 28 serious events
Other events: 285 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rapastinel
n=617 participants at risk
Rapastinel 450 milligrams (mg) intravenous (IV) open label weekly or every two weeks, based on investigator's discretion for 52 Weeks.
|
|---|---|
|
Psychiatric disorders
Suicidal ideation
|
0.65%
4/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Psychiatric disorders
Major depression
|
0.32%
2/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Surgical and medical procedures
Abortion induced
|
0.22%
1/455 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.22%
1/455 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Infections and infestations
Abscess jaw
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Vascular disorders
Accelerated hypertension
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Psychiatric disorders
Alcohol use disorder
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Infections and infestations
Appendiceal abscess
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Infections and infestations
Appendicitis
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Infections and infestations
Appendicitis perforated
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Nervous system disorders
Ataxia
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Cardiac disorders
Atrial fibrillation
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Injury, poisoning and procedural complications
Concussion
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Psychiatric disorders
Depression
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.22%
1/455 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Infections and infestations
Epstein-Barr virus infection
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Injury, poisoning and procedural complications
Fall
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Infections and infestations
Gastroenteritis
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Infections and infestations
Gun shot wound
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Injury, poisoning and procedural complications
Head injury
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Nervous system disorders
Headache
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumomediastinum
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Nervous system disorders
Presyncope
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Injury, poisoning and procedural complications
Procedural dizziness
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Injury, poisoning and procedural complications
Procedural nausea
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Renal and urinary disorders
Renal failure
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.16%
1/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
Other adverse events
| Measure |
Rapastinel
n=617 participants at risk
Rapastinel 450 milligrams (mg) intravenous (IV) open label weekly or every two weeks, based on investigator's discretion for 52 Weeks.
|
|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
14.4%
89/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Infections and infestations
Nasopharyngitis
|
12.6%
78/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Nervous system disorders
Headache
|
11.5%
71/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Nervous system disorders
Dysgeusia
|
7.0%
43/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Gastrointestinal disorders
Nausea
|
7.0%
43/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.0%
37/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Psychiatric disorders
Insomnia
|
5.8%
36/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
|
Investigations
Weight increased
|
5.7%
35/617 • Adverse Events were collected up to 52 weeks during the OLTP.
The Safety Population consisted of all screened patients who received at least 1 dose of rapastinel during the OLTP of the study.
|
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