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This double-blind, randomized study will evaluate the efficacy, safety and tolerability of ALKS 3831 in subjects with schizophrenia and alcohol use disorder (AUD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Samidorphan + olanzapine (ALKS 3831) | Experimental | Active study drug |
|
| Placebo + olanzapine | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Samidorphan + olanzapine (ALKS 3831) | Drug | Oral tablet, taken once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Independent Adjudication Committee (IAC) Adjudicated Event of Exacerbation of Disease (EEDS) | EEDS was defined as any of the following occurring during the double-blind period & was related to worsening of disease symptoms, as confirmed by the Independent Adjudication Committee (IAC):
3a. Score >= 5 for subjects at a 2nd ad hoc visit with a score <=3 at randomization 3b. Score >= 6 for subjects at a 2nd ad hoc visit with a score =4 at randomization 4. Engagement in self injury, aggressive behavior, or suicidal/homicidal ideation 5. Initiation of rescue medication, including increase in olanzapine dosage initially prescribed at randomization 6. ER visit 7. Subject withdraws or PI discontinues subject for lack of efficacy, lost to follow-up, or withdrawal by subject 8. Arrest or incarceration related to subject's underlying disease | Up to 15 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Events of Exacerbation of Disease (EEDS) | EEDS was defined as any of the following occurring during the double-blind period & was related to worsening of disease symptoms, as confirmed by the Independent Adjudication Committee (IAC):
3a. Score >= 5 for subjects at a 2nd ad hoc visit with a score <=3 at randomization 3b. Score >= 6 for subjects at a 2nd ad hoc visit with a score =4 at randomization 4. Engagement in self injury, aggressive behavior, or suicidal/homicidal ideation 5. Initiation of rescue medication, including increase in olanzapine dosage initially prescribed at randomization 6. ER visit 7. Subject withdraws or PI discontinues subject for lack of efficacy, lost to follow-up, or withdrawal by subject 8. Arrest or incarceration related to subject's underlying disease |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David McDonnell, MD | Alkermes, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alkermes Investigational Site | Little Rock | Arkansas | 72211 | United States | ||
| Alkermes Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32160422 | Result | Brunette MF, Correll CU, O'Malley SS, McDonnell D, DiPetrillo L, Jiang Y, Simmons A, Silverman BL, Citrome L, Green AI. Olanzapine Plus Samidorphan (ALKS 3831) in Schizophrenia and Comorbid Alcohol Use Disorder: A Phase 2, Randomized Clinical Trial. J Clin Psychiatry. 2020 Mar 10;81(2):19m12786. doi: 10.4088/JCP.19m12786. |
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After screening, subjects began a 4-week open-label olanzapine dosing period followed by a 2- week open-label ALKS 3831 period. Subjects who did not tolerate ALKS 3831 during the second open-label period were discontinued from the study prior to randomization. A total of 300 subjects were enrolled in the study, and 255 completed the open-label olanzapine period. 234 subjects were randomized following the open-label ALKS 3831 period, however, 5 subjects discontinued prior to receiving treatment.
Subjects were adults with a diagnosis of schizophrenia and Alcohol Use Disorder (AUD). Subjects must also have recently experienced an exacerbation of disease symptoms (eg, hospitalization), but could not exceed a pre-defined level of symptom severity at the time of screening (as measured by assessments like the Positive and Negative Symptom Scale [PANSS] and Clinical Global Impression- Severity [CGI-S]).
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| ID | Title | Description |
|---|---|---|
| FG000 | Open-label ALKS 3831 | Oral tablet, taken once daily ALKS 3831: Olanzapine (dose level determined by investigator) + Samidorphan (10mg) |
| FG001 | ALKS 3831 | Oral tablet, taken once daily ALKS 3831: Olanzapine (dose level determined by investigator) + Samidorphan (10mg) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Open-Label ALKS 3831 Period |
|
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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 | Mar 1, 2016 | Jun 10, 2021 |
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| Placebo + olanzapine | Drug | Oral tablet, taken once daily |
|
| Up to 15 months |
| Number and Percentage of Subjects With at Least 1 Level Decrease in World Health Organization (WHO) Drinking Risk Level From Baseline to Week 24 of the Double-blind Treatment (Study Week 27) | Alcohol consumption per day = (total number of drinks x 14 gram) / (total number of days) WHO criteria for risk of alcohol consumption on a single drinking day: Abstinence- Males: 0 g; Females- 0 g Low Risk- Males: 1-40 g; Females: 1-20 g Medium Risk- Males: 41- 60 g; Females: 21- 40 g High Risk- Males: 61-100 g; Females: 41-60 g Very High Risk- Males: >= 101 g; Females: >= 61 g | 24 weeks |
| Springdale |
| Arkansas |
| 72764 |
| United States |
| Alkermes Investigational Site | Anaheim | California | 92805 | United States |
| Alkermes Investigational Site | Culver City | California | 90230 | United States |
| Alkermes Investigational Site | Garden Grove | California | 92845 | United States |
| Alkermes Investigational Site | Irvine | California | 92617 | United States |
| Alkermes Investigational Site | La Jolla | California | 92037 | United States |
| Alkermes Investigational Site | Long Beach | California | 90822 | United States |
| Alkermes Investigational Site | National City | California | 91950 | United States |
| Alkermes Investigational Site | Oakland | California | 94612 | United States |
| Alkermes Investigational Site | Oceanside | California | 92056 | United States |
| Alkermes Investigational Site | Orange | California | 92868 | United States |
| Alkermes Investigational Site | San Diego | California | 92123 | United States |
| Alkermes Investigational Site | San Francisco | California | 94121 | United States |
| Alkermes Investigational Site | Torrance | California | 90502 | United States |
| Alkermes Investigational Site | Washington D.C. | District of Columbia | 20016 | United States |
| Alkermes Investigational Site | Fort Lauderdale | Florida | 33308 | United States |
| Alkermes Investigational Site | Leesburg | Florida | 34748 | United States |
| Alkermes Investigational Site | Maitland | Florida | 32751 | United States |
| Alkermes Investigational Site | Miami | Florida | 33122 | United States |
| Alkermes Investigational Site | Miami | Florida | 33136 | United States |
| Alkermes Investigational Site | North Miami | Florida | 33021 | United States |
| Alkermes Investigational Site | Oakland Park | Florida | 33334 | United States |
| Alkermes Investigational Site | Orlando | Florida | 32803 | United States |
| Alkermes Investigational Site | Tampa | Florida | 33613 | United States |
| Alkermes Investigational Site | Atlanta | Georgia | 30308 | United States |
| Alkermes Investigational Site | Augusta | Georgia | 30912 | United States |
| Alkermes Investigational Site | Decatur | Georgia | 30030 | United States |
| Alkermes Investigational Site | Chicago | Illinois | 60640 | United States |
| Alkermes Investigational Site | Hoffman Estates | Illinois | 60169 | United States |
| Alkermes Investigational Site | Oak Brook | Illinois | 60523 | United States |
| Alkermes Investigational Site | Shreveport | Louisiana | 71101 | United States |
| Alkermes Investigational Site | Worcester | Massachusetts | 01605 | United States |
| Alkermes Investigational Site | Flowood | Mississippi | 39232 | United States |
| Alkermes Investigational Site | Creve Coeur | Missouri | 63141 | United States |
| Alkermes Investigational Site | Kansas City | Missouri | 64108 | United States |
| Alkermes Investigational Site | St Louis | Missouri | 63118 | United States |
| Alkermes Investigational Site | Las Vegas | Nevada | 89102 | United States |
| Alkermes Investigational Site | Claremont | New Hampshire | 03743 | United States |
| Alkermes Investigational Site | Nashua | New Hampshire | 03060 | United States |
| Alkermes Investigational Site | Neptune City | New Jersey | 07753 | United States |
| Alkermes Investigational Site | Cedarhurst | New York | 11516 | United States |
| Alkermes Investigational Site | Jamaica | New York | 11423 | United States |
| Alkermes Investigational Site | New York | New York | 10021 | United States |
| Alkermes Investigational Site | New York | New York | 10032 | United States |
| Alkermes Investigational Site | New York | New York | 10035 | United States |
| Alkermes Investigational Site | Rochester | New York | 14642 | United States |
| Alkermes Investigational Site | Staten Island | New York | 10312 | United States |
| Alkermes Investigational Site | Dayton | Ohio | 45417 | United States |
| Alkermes Investigational Site | Oklahoma City | Oklahoma | 73112 | United States |
| Alkermes Investigational Site | Scranton | Pennsylvania | 18503 | United States |
| Alkermes Investigational Site | Charleston | South Carolina | 29401 | United States |
| Alkermes Investigational Site | Charleston | South Carolina | 29407 | United States |
| Alkermes Investigational Site | Charleston | South Carolina | 29425 | United States |
| Alkermes Investigational Site | Austin | Texas | 78754 | United States |
| Alkermes Investigational Site | Dallas | Texas | 75214 | United States |
| Alkermes Investigational Site | DeSoto | Texas | 75115 | United States |
| Alkermes Investigational Site | Bellevue | Washington | 98007 | United States |
| Alkermes Investigational Site | Burgas | 8000 | Bulgaria |
| Alkermes Investigational Site | Kazanlak | 6100 | Bulgaria |
| Alkermes Investigational Site | Lovech | 5500 | Bulgaria |
| Alkermes Investigational Site | Novi Iskar | 1282 | Bulgaria |
| Alkermes Investigational Site | Sofia | 1606 | Bulgaria |
| Alkermes Investigational Site | Tserova Koria | 8260 | Bulgaria |
| Alkermes Investigational Site | Varna | 9002 | Bulgaria |
| Alkermes Investigational Site | Varna | 9020 | Bulgaria |
| Alkermes Investigational Site | Vratsa | 3000 | Bulgaria |
| Alkermes Investigational Site | Bełchatów | 97-400 | Poland |
| Alkermes Investigational Site | Bialystok | 15-464 | Poland |
| Alkermes Investigational Site | Gdansk | 80-546 | Poland |
| Alkermes Investigational Site | Lublin | 20-109 | Poland |
| FG002 | Olanzapine + Placebo | Oral tablet, taken once daily Olanzapine dose level determined by investigator |
| COMPLETED |
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| NOT COMPLETED |
|
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| Post- Randomization Period |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ALKS 3831 | Oral tablet, taken once daily ALKS 3831: Olanzapine (dose level determined by investigator) + Samidorphan (10mg) |
| BG001 | Olanzapine + Placebo | Oral tablet, taken once daily Olanzapine dose level determined by investigator |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | 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 | Number | participants |
| ||||||||||||||||
| Height | Mean | Standard Deviation | centimeters |
| |||||||||||||||
| Weight | Mean | Standard Deviation | kilograms |
| |||||||||||||||
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
| |||||||||||||||
| Body Mass Index (BMI) Group | Count of Participants | Participants |
|
| 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 | Number of Participants With Independent Adjudication Committee (IAC) Adjudicated Event of Exacerbation of Disease (EEDS) | EEDS was defined as any of the following occurring during the double-blind period & was related to worsening of disease symptoms, as confirmed by the Independent Adjudication Committee (IAC):
3a. Score >= 5 for subjects at a 2nd ad hoc visit with a score <=3 at randomization 3b. Score >= 6 for subjects at a 2nd ad hoc visit with a score =4 at randomization 4. Engagement in self injury, aggressive behavior, or suicidal/homicidal ideation 5. Initiation of rescue medication, including increase in olanzapine dosage initially prescribed at randomization 6. ER visit 7. Subject withdraws or PI discontinues subject for lack of efficacy, lost to follow-up, or withdrawal by subject 8. Arrest or incarceration related to subject's underlying disease | Efficacy analyses were carried out using the intent to treat (ITT) population, i.e. all randomized subjects who received at least one dose of study drug post-randomization | Posted | Count of Participants | Participants | Up to 15 months |
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| Secondary | Number of Events of Exacerbation of Disease (EEDS) | EEDS was defined as any of the following occurring during the double-blind period & was related to worsening of disease symptoms, as confirmed by the Independent Adjudication Committee (IAC):
3a. Score >= 5 for subjects at a 2nd ad hoc visit with a score <=3 at randomization 3b. Score >= 6 for subjects at a 2nd ad hoc visit with a score =4 at randomization 4. Engagement in self injury, aggressive behavior, or suicidal/homicidal ideation 5. Initiation of rescue medication, including increase in olanzapine dosage initially prescribed at randomization 6. ER visit 7. Subject withdraws or PI discontinues subject for lack of efficacy, lost to follow-up, or withdrawal by subject 8. Arrest or incarceration related to subject's underlying disease | Efficacy analyses were carried out using the intent to treat (ITT) population, i.e. all randomized subjects who received at least one dose of study drug post-randomization | Posted | Number | Events | Up to 15 months |
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| Secondary | Number and Percentage of Subjects With at Least 1 Level Decrease in World Health Organization (WHO) Drinking Risk Level From Baseline to Week 24 of the Double-blind Treatment (Study Week 27) | Alcohol consumption per day = (total number of drinks x 14 gram) / (total number of days) WHO criteria for risk of alcohol consumption on a single drinking day: Abstinence- Males: 0 g; Females- 0 g Low Risk- Males: 1-40 g; Females: 1-20 g Medium Risk- Males: 41- 60 g; Females: 21- 40 g High Risk- Males: 61-100 g; Females: 41-60 g Very High Risk- Males: >= 101 g; Females: >= 61 g | Efficacy analyses were carried out using subjects from the intent to treat (ITT) population with postbaseline data on drinking habits. | Posted | Count of Participants | Participants | 24 weeks |
|
|
Adverse events are presented for the randomized, double-blind period (9-15 months) as well as the 2 week open-label ALKS 3831 (olanzapine + samidorphan) period for a total timeframe of up to 62 weeks.
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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 | Open- Label ALKS 3831 | A 2-week open-label period; all subjects received olanzapine (dose determined by investigator) + 10 mg samidorphan | 0 | 255 | 4 | 255 | 0 | 255 |
| EG001 | Olanzapine + Placebo | All randomized subjects who received at least 1 dose of study drug (olanzapine + placebo) during the double-blind treatment period | 1 | 117 | 12 | 117 | 19 | 117 |
| EG002 | ALKS 3831 | All randomized subjects who received at least 1 dose of ALKS 3831 (olanzapine + samidorphan) during the double-blind treatment period. | 1 | 112 | 7 | 112 | 26 | 112 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Parotitis | Infections and infestations | Non-systematic Assessment |
| ||
| Alcohol poisoning | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| Fall | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Electrocardiogram abnormal | Investigations | Non-systematic Assessment |
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| Chronic obstructive pulmonary disease | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Convulsion | Nervous system disorders | Non-systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Non-systematic Assessment |
| ||
| Transient ischaemic attack | Nervous system disorders | Non-systematic Assessment |
| ||
| Alcoholism | Psychiatric disorders | Non-systematic Assessment |
| ||
| Schizophrenia, paranoid type | Psychiatric disorders | Non-systematic Assessment |
| ||
| Schizophrenia | Psychiatric disorders | Non-systematic Assessment |
| ||
| Paranoia | Psychiatric disorders | Non-systematic Assessment |
| ||
| Psychotic disorder | Psychiatric disorders | Non-systematic Assessment |
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| Aggression | Psychiatric disorders | Non-systematic Assessment |
| ||
| Agitation | Psychiatric disorders | Non-systematic Assessment |
| ||
| Disturbance in social behavior | Psychiatric disorders | Non-systematic Assessment |
| ||
| Suicidal ideation | Psychiatric disorders | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Weight increased | Investigations | Non-systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Non-systematic Assessment |
| ||
| Nasopharyngitis | Infections and infestations | Non-systematic Assessment |
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Should an Investigator desire to disclose study results, Sponsor will review the results disclosure prior to public release and can embargo the disclosure for a period of at least 60 days. Revisions to the disclosure will be negotiated in good faith. For a multicenter study the Investigators agree to publish/publicly present the results together with the other sites for the 12 month period after study results are available unless Sponsor grants written permission in advance
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Corporate and R&D Communications | Alkermes | 781-609-7000 | Gretchen.Murphy@alkermes.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 20, 2017 | Jun 10, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
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| ID | Term |
|---|---|
| C000606131 | 3-carboxamido-4-hydroxynaltrexone |
| D000077152 | Olanzapine |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Adverse Event |
|
| Non- compliance with study drug |
|
| Physician Decision |
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| Protocol Violation |
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| Lack of Efficacy |
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| Non-compliance with study procedures |
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| Received prohibitive treatment |
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| Relocation |
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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 |
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| 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 |
|
| Unknown or Not Reported |
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| Bulgaria |
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| Poland |
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| Normal (18.5 to <25) |
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| Overweight (25 to <30) |
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| Obese (>= 30) |
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