Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Depression, Alkermes, ALKS 5461, Samidorphan
Brief summary
This study will evaluate the efficacy and safety of ALKS 5461.
Interventions
DRUGALKS 5461
Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
DRUGPlacebo
Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
Sponsors
Alkermes, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Have a Body Mass Index (BMI) of 18.0 to 40.0 kg/m2, inclusive * Agree to use an acceptable method of contraception for the duration of the study * Have a Major Depressive Disorder (MDD) primary diagnosis * Have no more than 2 inadequate responses to antidepressant therapy (ADT) in the current Major Depressive Episode (MDE) * Additional criteria may apply
Exclusion criteria
* Have a current primary Axis-I disorder other than MDD * Have used opioid agonists (eg, codeine, oxycodone, tramadol, morphine) or opioid antagonists (eg, naloxone, naltrexone) within 14 days * Have received electroconvulsive therapy treatment within the last 2 years or received more than one course of electroconvulsive treatment during lifetime * Have attempted suicide within the past 2 years * Have a positive test for drugs of abuse * Are pregnant, planning to become pregnant, or breastfeeding * Have a history of intolerance, allergy, or hypersensitivity to buprenorphine or opioid antagonists (eg, naltrexone, naloxone) * Have had a significant blood loss or blood donation within 60 days * Additional criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Treatment (Week 6) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score | Baseline and week 6 | The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events (AEs) | 6 weeks | — |
| Proportion of Patients Who Exhibited Treatment Response (MADRS-10) | 6 weeks | The proportion of subjects demonstrating MADRS-10 treatment response, defined as a ≥ 50% reduction in MADRS-10 score from baseline to the end of the efficacy period (week 6). |
| Remission Rate | 6 weeks | The proportion of subjects achieving remission, defined as a MADRS-10 score of ≤ 10 at the end of the efficacy period. |
Countries
Bulgaria, United States
Participant flow
Recruitment details
Subjects were diagnosed with major depressive disorder (MDD) and had an inadequate response to 1 or 2 adequate courses of treatment with a commercially available antidepressant therapy (ADT) during the current major depressive episode (MDE). All subjects continued ADT for the duration of the study.
Pre-assignment details
2 cohorts of subjects were enrolled: Group 1- subjects with baseline HAM-D17 score ≥ 20; Group 2- subjects with baseline HAM-D17 score 18-19. Only Group 1 was included in the efficacy analysis. Study included a 4-week pbo run-in period prior to the 6-week treatment period. In Group 1, 102 subjects did not meet criteria for randomization.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 ALKS 5461 2mg/2mg Randomized to ALKS 5461 2mg/2mg | 147 |
| Group 1 Placebo Randomized to placebo | 148 |
| Group 2 ALKS 5461 2mg/2mg Randomized to ALKS 5461 2mg/2mg | 15 |
| Group 2 Placebo Randomized to placebo | 15 |
| Total | 325 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 0 | 0 |
| Overall Study | Failure to meet eligibility criteria | 0 | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 5 | 4 | 0 | 1 |
| Overall Study | Non-compliance | 0 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 |
| Overall Study | Site Excluded | 5 | 5 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 6 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Group 1 ALKS 5461 2mg/2mg | Group 1 Placebo | Group 2 ALKS 5461 2mg/2mg | Group 2 Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 12.31 | 48.1 years STANDARD_DEVIATION 12.51 | 47.5 years STANDARD_DEVIATION 12.63 | 45.9 years STANDARD_DEVIATION 11.44 | 47.7 years STANDARD_DEVIATION 12.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 29 Participants | 2 Participants | 1 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 124 Participants | 119 Participants | 13 Participants | 14 Participants | 270 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 33 Participants | 3 Participants | 2 Participants | 71 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 106 Participants | 115 Participants | 12 Participants | 13 Participants | 246 Participants |
| Region of Enrollment Bulgaria | 29 Participants | 20 Participants | 1 Participants | 3 Participants | 53 Participants |
| Region of Enrollment United States | 118 Participants | 128 Participants | 14 Participants | 12 Participants | 272 Participants |
| Sex: Female, Male Female | 88 Participants | 94 Participants | 8 Participants | 7 Participants | 197 Participants |
| Sex: Female, Male Male | 59 Participants | 54 Participants | 7 Participants | 8 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 147 | 0 / 148 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 39 / 147 | 24 / 148 | 11 / 15 | 8 / 15 |
| serious Total, serious adverse events | 0 / 147 | 1 / 148 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change From Baseline to End of Treatment (Week 6) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score
The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of 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.
Time frame: Baseline and week 6
Population: The Full Analysis Set (FAS) consists of subjects in the Group 1 Safety Population who have at least 1 post-randomization assessment of MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ALKS 5461 2mg/2mg | Change From Baseline to End of Treatment (Week 6) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score | -4.8 units on a scale | Standard Error 0.67 |
| Placebo | Change From Baseline to End of Treatment (Week 6) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score | -4.6 units on a scale | Standard Error 0.66 |
p-value: 0.78295% CI: [-2.1, 1.6]Mixed Models Analysis
Secondary
Number of Subjects With Adverse Events (AEs)
Time frame: 6 weeks
Population: Safety population consisted of subjects who were identified as placebo non-responders at the end of the double-blind placebo run-in period and received at least one dose of randomized study drug (ie, placebo or ALKS 5461) subsequent to randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALKS 5461 2mg/2mg | Number of Subjects With Adverse Events (AEs) | 63 Participants |
| Placebo | Number of Subjects With Adverse Events (AEs) | 51 Participants |
| Group 2 ALKS 5461 2mg/2mg | Number of Subjects With Adverse Events (AEs) | 11 Participants |
| Group 2 Placebo | Number of Subjects With Adverse Events (AEs) | 8 Participants |
Secondary
Proportion of Patients Who Exhibited Treatment Response (MADRS-10)
The proportion of subjects demonstrating MADRS-10 treatment response, defined as a ≥ 50% reduction in MADRS-10 score from baseline to the end of the efficacy period (week 6).
Time frame: 6 weeks
Population: The FAS consists of subjects in the Group 1 Safety Population who have at least 1 post-randomization assessment of MADRS total score.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALKS 5461 2mg/2mg | Proportion of Patients Who Exhibited Treatment Response (MADRS-10) | 24 Participants |
| Placebo | Proportion of Patients Who Exhibited Treatment Response (MADRS-10) | 21 Participants |
Secondary
Remission Rate
The proportion of subjects achieving remission, defined as a MADRS-10 score of ≤ 10 at the end of the efficacy period.
Time frame: 6 weeks
Population: The FAS consists of subjects in the Group 1 Safety Population who have at least 1 post-randomization assessment of MADRS total score.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALKS 5461 2mg/2mg | Remission Rate | 20 Participants |
| Placebo | Remission Rate | 18 Participants |