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This study will evaluate the efficacy, safety, and tolerability of adjunctive ALKS 5461 in adults who have treatment refractory MDD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALKS 5461 | Experimental | Sublingual tablets |
|
| ALKS 5461 Placebo | Placebo Comparator | Sublingual tablets |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALKS 5461 | Drug | Samidorphan + buprenorphine, administered sublingually |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to the End of Treatment (EOT) in the Montgomery Asberg Depression Rating Scale-10 (MADRS-10) Scores | 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. | Baseline and 5 weeks for Stage 1, Baseline and 6 weeks for Stage 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Montgomery Asberg Depression Rating Scale (MADRS) Response Rate | 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). |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sanjeev Pathak, MD | Alkermes, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alkermes Investigational Site | Tucson | Arizona | 85712 | United States | ||
| Alkermes Investigational Site |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | S1: Placebo | Randomized to placebo in Stage 1 |
| FG001 | S1: ALKS 5461 2mg/2mg | Randomized to ALKS 5461 2mg/2mg in Stage 1 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Stage 1 |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 25, 2018 | Feb 19, 2021 |
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| ALKS 5461 Placebo |
| Drug |
Placebo tablet, administered sublingually |
|
| Baseline and 5 weeks for Stage 1, Baseline and 6 weeks for Stage 2 |
| Montgomery Asberg Depression Rating Scale (MADRS) Remission Rate | The percentage of subjects achieving remission, defined as a subject with a score \ | 5 weeks for Stage 1, 6 weeks for Stage 2 |
| Little Rock |
| Arkansas |
| 72211 |
| United States |
| Alkermes Investigational Site | Los Alamitos | California | 90720 | United States |
| Alkermes Investigational Site | Oceanside | California | 92056 | United States |
| Alkermes Investigational Site | Pico Rivera | California | 90660 | United States |
| Alkermes Investigational Site | Redlands | California | 92374 | United States |
| Alkermes Investigational Site | Santa Ana | California | 92705 | United States |
| Alkermes Investigational Site | Sherman Oaks | California | 91403 | United States |
| Alkermes Investigational Site | Temecula | California | 92591 | United States |
| Alkermes Investigative Site | Upland | California | 91786 | United States |
| Alkermes Investigational Site | Hollywood | Florida | 33024 | United States |
| Alkermes Investigational Site | Jacksonville | Florida | 32256 | United States |
| Alkermes Investigational Site | Lauderhill | Florida | 33319 | United States |
| Alkermes Investigational Site | Orlando | Florida | 32801 | United States |
| Alkermes Investigative Site | Palm Bay | Florida | 32905 | United States |
| Alkermes Investigational Site | Atlanta | Georgia | 30341 | United States |
| Alkermes Investigational Site | Decatur | Georgia | 30030 | United States |
| Alkermes Investigational Site | Pikesville | Maryland | 21208 | United States |
| Alkermes Investigational Site | O'Fallon | Missouri | 63368 | United States |
| Alkermes Investigational Site | Jamaica | New York | 11432 | United States |
| Alkermes Investigational Site | Mount Kisco | New York | 10549 | United States |
| Alkermes Investigational Site | Canton | Ohio | 44720 | United States |
| Alkermes Investigational Site | Cincinnati | Ohio | 45215 | United States |
| Alkermes Investigational Site | Oklahoma City | Oklahoma | 73112 | United States |
| Alkermes Investigational Site | Allentown | Pennsylvania | 18104 | United States |
| Alkermes Investigational Site | Memphis | Tennessee | 38119 | United States |
| Alkermes Investigational Site | Dallas | Texas | 75390 | United States |
| Alkermes Investigational Site | DeSoto | Texas | 75115 | United States |
| Alkermes Investigational Site | Woodstock | Vermont | 05091 | United States |
| Alkermes Investigative Site | Bellevue | Washington | 98007 | United States |
| Alkermes Investigational Site | Frankston | Victoria | 3199 | Australia |
| Alkermes Investigational Site | Noble Park | Victoria | 3174 | Australia |
| Alkermes Investigational Site | Richmond | Victoria | 3121 | Australia |
| Alkermes Investigational Site | San Juan | 00918 | Puerto Rico |
| Alkermes Investigational Site | San Juan | 00926-3160 | Puerto Rico |
| FG002 | S2: Placebo | Randomized to placebo in Stage 2 |
| FG003 | S2: ALKS 5461 2mg/2mg | Randomized to ALKS 5461 2mg/2mg in Stage 2 |
| COMPLETED |
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| NOT COMPLETED |
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| Stage 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | S1: Placebo | Randomized to placebo in Stage 1. |
| BG001 | S1: ALKS 5461 2mg/2mg | Randomized to ALKS 5461 2mg/2mg in Stage 1. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to the End of Treatment (EOT) in the Montgomery Asberg Depression Rating Scale-10 (MADRS-10) Scores | 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and 5 weeks for Stage 1, Baseline and 6 weeks for Stage 2 |
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| Secondary | Montgomery Asberg Depression Rating Scale (MADRS) Response Rate | 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). | 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. | Posted | Count of Participants | Participants | Baseline and 5 weeks for Stage 1, Baseline and 6 weeks for Stage 2 |
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| Secondary | Montgomery Asberg Depression Rating Scale (MADRS) Remission Rate | The percentage of subjects achieving remission, defined as a subject with a score \ | 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. | Posted | Count of Participants | Participants | 5 weeks for Stage 1, 6 weeks for Stage 2 |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | S1: Placebo | Randomized to placebo in Stage 1 | 0 | 198 | 0 | 198 | 43 | 198 |
| EG001 | S1: ALKS 5461 2mg/2mg | Randomized to ALKS 5461 2mg/2mg in Stage 1 | 0 | 80 | 1 | 80 | 56 | 80 |
| EG002 | S2: Placebo | Randomized to placebo in Stage 2 | 0 | 64 | 1 | 64 | 3 | 64 |
| EG003 | S2: ALKS 5461 2mg/2mg | Randomized to ALKS 5461 2mg/2mg in Stage 2 | 0 | 63 | 0 | 63 | 29 | 63 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Serotonin Syndrome | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
| |
| Meningioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (22.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (22.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (22.0) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
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| Sedation | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
| |
| Abnormal dreams | Psychiatric disorders | MedDRA (22.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (22.0) | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eva Stroynowski | Alkermes | 781-609-7000 | eva.stroynowski@alkermes.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 2, 2019 | Feb 19, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000618349 | ALKS 5461 |
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| Lack of Efficacy |
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| Lost to Follow-up |
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| Physician Decision |
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| Withdrawal by Subject |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
|
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Australia |
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| Superiority |
Hypothesis tests were two-sided with an alpha of 0.05 . |
| OG003 | S2: ALKS 5461 2mg/2mg | Randomized to ALKS 5461 2mg/2mg in Stage 2 |
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| OG003 | S2: ALKS 5461 2mg/2mg | Randomized to ALKS 5461 2mg/2mg in Stage 2 |
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