A Study of ALKS 3831 in Subjects With Schizophrenia and Alcohol Use Disorder

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 2, Efficacy, Safety and Tolerability Study of ALKS 3831 in Schizophrenia With Alcohol Use Disorder

Conditions
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Schizophrenia, Alcohol Use Disorder

Intervention / Treatment
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* Drug: Samidorphan + olanzapine (ALKS 3831)
* Drug: Placebo + olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a BMI between 18.0 and 40.0 kg/m2, inclusive Has a diagnosis of schizophrenia Has a diagnosis of alcohol use disorder (AUD) Has experienced an acute exacerbation of schizophrenia within the past 6 months Additional criteria may apply Exclusion Criteria: Is pregnant or breastfeeding Had first lifetime psychotic episode less than 1 year before screening or has experienced only a single lifetime psychotic episode Has a known or suspected intolerance, allergy, or hypersensitivity to olanzapine Has current or pending legal charges with the potential for incarceration Has a positive drug screen for opiates Additional criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Samidorphan + olanzapine (ALKS 3831)<br>Active study drug | Drug: Samidorphan + olanzapine (ALKS 3831)<br>* Oral tablet, taken once daily<br>|
| Placebo Comparator: Placebo + olanzapine<br> | Drug: Placebo + olanzapine<br>* Oral tablet, taken once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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): Hospitalization (includes psychiatric& treatment of alcohol intoxication/withdrawal) >= 25% or >= 15 point increase from randomization in PANSS total score PANSS items score of P1, P2, P3, P6, P7 or G8 that meets 1 of the following: 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 | 

Secondary Outcome Measures

| Outcome Measure | 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): Hospitalization(includes psychiatric & treatment of alcohol intoxication/withdrawal) >= 25% or >= 15 point increase from randomization in PANSS total score PANSS items score of P1, P2, P3, P6, P7 or G8 that meets 1 of the following: 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alkermes, Schizophrenia, Alcohol Use Disorder, ALKS 3831