Trial Outcomes & Findings for A Study of ALKS 5461 for Treatment Refractory Major Depressive Disorder (MDD) (NCT NCT03188185)
NCT ID: NCT03188185
Last Updated: 2021-04-08
Results Overview
The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of Major Depressive Disorder (MDD) symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
278 participants
Primary outcome timeframe
Baseline and 5 weeks for Stage 1, Baseline and 6 weeks for Stage 2
Results posted on
2021-04-08
Participant Flow
Subjects were diagnosed with treatment refractory major depressive disorder (MDD), defined as having at least 2 inadequate responses to commercially available antidepressant therapies (ADTs) during the current major depressive episode (MDE). All subjects continued to take an approved ADT for the duration of the study.
This was a Sequential Parallel Comparison Design (SPCD) study comprised of 2 stages. In Stage 1 subjects were randomized to ALKS 5461 or placebo. In Stage 2 only placebo non-responders from Stage 1 were re-randomized to ALKS 5461 or placebo.
Participant milestones
| Measure |
S1: Placebo
Randomized to placebo in Stage 1
|
S1: ALKS 5461 2mg/2mg
Randomized to ALKS 5461 2mg/2mg in Stage 1
|
S2: Placebo
Randomized to placebo in Stage 2
|
S2: ALKS 5461 2mg/2mg
Randomized to ALKS 5461 2mg/2mg in Stage 2
|
|---|---|---|---|---|
|
Stage 1
STARTED
|
198
|
80
|
0
|
0
|
|
Stage 1
COMPLETED
|
179
|
64
|
0
|
0
|
|
Stage 1
NOT COMPLETED
|
19
|
16
|
0
|
0
|
|
Stage 2
STARTED
|
0
|
0
|
64
|
63
|
|
Stage 2
COMPLETED
|
0
|
0
|
55
|
57
|
|
Stage 2
NOT COMPLETED
|
0
|
0
|
9
|
6
|
Reasons for withdrawal
| Measure |
S1: Placebo
Randomized to placebo in Stage 1
|
S1: ALKS 5461 2mg/2mg
Randomized to ALKS 5461 2mg/2mg in Stage 1
|
S2: Placebo
Randomized to placebo in Stage 2
|
S2: ALKS 5461 2mg/2mg
Randomized to ALKS 5461 2mg/2mg in Stage 2
|
|---|---|---|---|---|
|
Stage 1
Adverse Event
|
4
|
12
|
0
|
0
|
|
Stage 1
Lack of Efficacy
|
0
|
2
|
0
|
0
|
|
Stage 1
Lost to Follow-up
|
6
|
1
|
0
|
0
|
|
Stage 1
Withdrawal by Subject
|
9
|
0
|
0
|
0
|
|
Stage 1
Identified as a professional patient
|
0
|
1
|
0
|
0
|
|
Stage 2
Adverse Event
|
0
|
0
|
2
|
4
|
|
Stage 2
Lack of Efficacy
|
0
|
0
|
3
|
0
|
|
Stage 2
Lost to Follow-up
|
0
|
0
|
1
|
0
|
|
Stage 2
Physician Decision
|
0
|
0
|
0
|
1
|
|
Stage 2
Withdrawal by Subject
|
0
|
0
|
3
|
1
|
Baseline Characteristics
A Study of ALKS 5461 for Treatment Refractory Major Depressive Disorder (MDD)
Baseline characteristics by cohort
| Measure |
S1: Placebo
n=198 Participants
Randomized to placebo in Stage 1.
|
S1: ALKS 5461 2mg/2mg
n=80 Participants
Randomized to ALKS 5461 2mg/2mg in Stage 1.
|
Total
n=278 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
44 years
n=5 Participants
|
40.5 years
n=7 Participants
|
43 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
139 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
196 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
59 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
31 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
167 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
237 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
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 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
|
24 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
160 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
223 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
176 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
248 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
22 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 5 weeks for Stage 1, Baseline and 6 weeks for Stage 2Population: Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS assessment in the respective stage.
The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of Major Depressive Disorder (MDD) symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.
Outcome measures
| Measure |
S1: Placebo
n=195 Participants
Randomized to placebo in Stage 1
|
S1: ALKS 5461 2mg/2mg
n=76 Participants
Randomized to ALKS 5461 2mg/2mg in Stage 1
|
S2: Placebo
n=64 Participants
Randomized to placebo in Stage 2
|
S2: ALKS 5461 2mg/2mg
n=63 Participants
Randomized to ALKS 5461 2mg/2mg in Stage 2
|
|---|---|---|---|---|
|
Change From Baseline to the End of Treatment (EOT) in the Montgomery Asberg Depression Rating Scale-10 (MADRS-10) Scores
|
-11.4 score on a scale
Standard Error 0.70
|
-13.9 score on a scale
Standard Error 1.12
|
-4.2 score on a scale
Standard Error 1.06
|
-4.7 score on a scale
Standard Error 1.11
|
SECONDARY outcome
Timeframe: Baseline and 5 weeks for Stage 1, Baseline and 6 weeks for Stage 2Population: Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS assessment in the respective stage.
The percentage of subjects demonstrating a MADRS-10 treatment response, defined as a \>/= 50% reduction in MADRS-10 score from baseline to the end of the efficacy period (Week 5 for Stage 1, Week 6 for Stage 2). The MADRS-10 scale is a measure of the severity of Major Depressive Disorder (MDD) symptoms and includes the following 10 items: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms).
Outcome measures
| Measure |
S1: Placebo
n=195 Participants
Randomized to placebo in Stage 1
|
S1: ALKS 5461 2mg/2mg
n=76 Participants
Randomized to ALKS 5461 2mg/2mg in Stage 1
|
S2: Placebo
n=64 Participants
Randomized to placebo in Stage 2
|
S2: ALKS 5461 2mg/2mg
n=63 Participants
Randomized to ALKS 5461 2mg/2mg in Stage 2
|
|---|---|---|---|---|
|
Montgomery Asberg Depression Rating Scale (MADRS) Response Rate
Yes
|
53 Participants
|
27 Participants
|
10 Participants
|
11 Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS) Response Rate
No
|
142 Participants
|
49 Participants
|
54 Participants
|
52 Participants
|
SECONDARY outcome
Timeframe: 5 weeks for Stage 1, 6 weeks for Stage 2Population: Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS assessment in the respective stage.
The percentage of subjects achieving remission, defined as a subject with a score \</= 10 at the end of the efficacy period (Week 5 for Stage 1, Week 6 for Stage 2). The MADRS-10 scale is a measure of the severity of Major Depressive Disorder (MDD) symptoms and includes the following 10 items: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms).the end of the efficacy period.
Outcome measures
| Measure |
S1: Placebo
n=195 Participants
Randomized to placebo in Stage 1
|
S1: ALKS 5461 2mg/2mg
n=76 Participants
Randomized to ALKS 5461 2mg/2mg in Stage 1
|
S2: Placebo
n=64 Participants
Randomized to placebo in Stage 2
|
S2: ALKS 5461 2mg/2mg
n=63 Participants
Randomized to ALKS 5461 2mg/2mg in Stage 2
|
|---|---|---|---|---|
|
Montgomery Asberg Depression Rating Scale (MADRS) Remission Rate
Yes
|
31 Participants
|
14 Participants
|
10 Participants
|
8 Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS) Remission Rate
No
|
164 Participants
|
62 Participants
|
54 Participants
|
55 Participants
|
Adverse Events
S1: Placebo
Serious events: 0 serious events
Other events: 43 other events
Deaths: 0 deaths
S1: ALKS 5461 2mg/2mg
Serious events: 1 serious events
Other events: 56 other events
Deaths: 0 deaths
S2: Placebo
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
S2: ALKS 5461 2mg/2mg
Serious events: 0 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
S1: Placebo
n=198 participants at risk
Randomized to placebo in Stage 1
|
S1: ALKS 5461 2mg/2mg
n=80 participants at risk
Randomized to ALKS 5461 2mg/2mg in Stage 1
|
S2: Placebo
n=64 participants at risk
Randomized to placebo in Stage 2
|
S2: ALKS 5461 2mg/2mg
n=63 participants at risk
Randomized to ALKS 5461 2mg/2mg in Stage 2
|
|---|---|---|---|---|
|
Nervous system disorders
Serotonin Syndrome
|
0.00%
0/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
1.2%
1/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
|
0.00%
0/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
1.6%
1/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
Other adverse events
| Measure |
S1: Placebo
n=198 participants at risk
Randomized to placebo in Stage 1
|
S1: ALKS 5461 2mg/2mg
n=80 participants at risk
Randomized to ALKS 5461 2mg/2mg in Stage 1
|
S2: Placebo
n=64 participants at risk
Randomized to placebo in Stage 2
|
S2: ALKS 5461 2mg/2mg
n=63 participants at risk
Randomized to ALKS 5461 2mg/2mg in Stage 2
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
5.1%
10/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
36.2%
29/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
25.4%
16/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Constipation
|
1.0%
2/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
11.2%
9/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
4.8%
3/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
2.0%
4/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
6.2%
5/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
9.5%
6/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
|
Nervous system disorders
Dizziness
|
2.0%
4/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
22.5%
18/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
12.7%
8/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
|
Nervous system disorders
Somnolence
|
2.5%
5/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
12.5%
10/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
1.6%
1/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
4.8%
3/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
7.1%
14/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
11.2%
9/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
11.1%
7/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
|
Nervous system disorders
Sedation
|
2.5%
5/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
10.0%
8/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
4.8%
3/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
|
Psychiatric disorders
Abnormal dreams
|
1.5%
3/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
5.0%
4/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
0.00%
0/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
4.8%
3/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
|
General disorders
Fatigue
|
1.5%
3/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
5.0%
4/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
1.6%
1/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
3.2%
2/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
2.5%
5/198 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
5.0%
4/80 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
1.6%
1/64 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
1.6%
1/63 • 5 weeks for Stage 1 and 6 weeks for Stage 2
The safety population includes all subjects who were randomized and received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place