A Study of ALKS 3831 in Adults With Schizophrenia

Study Overview
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Brief Summary
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This is a Phase 2, randomized, placebo-controlled multicenter study, which will be conducted in 2 parts. The study duration for each subject will be approximately 33 weeks and will include 25 study visits.

Official Title
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A Phase 2, Randomized, Multicenter, Safety, Tolerability, and Dose-Ranging Study of Samidorphan, a Component of ALKS 3831, in Adults With Schizophrenia Treated With Olanzapine

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Samidorphan (Low Dose)
* Drug: Samidorphan (Medium Dose)
* Drug: Samidorphan (High Dose)
* Drug: Placebo
* Drug: Olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 50 years, inclusive Body mass index (BMI) of 17-30 kg/m2, inclusive Diagnosis of schizophrenia that is clinically stable Exclusion Criteria: Initiated 1st antipsychotic treatment within the past 12 months and/or has had symptoms lasting <2 years Current diagnosis of alcohol or drug use disorder, moderate or severe Clinically significant or unstable medical illness, condition, or disorder Pregnant or breastfeeding Significant changes in diet or exercise regimen or plans to join a weight management program during the study Opioid medications taken within 14 days and/or need to take opioid medication during the study period History of hypersensitivity to or intolerance of olanzapine Use of olanzapine, clozapine, mesoridazine, chlorpromazine, or thioridazine for more than 1 week during the past year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Low Dose<br>Olanzapine + low dose samidorphan tablets taken once daily | Drug: Samidorphan (Low Dose)<br>* Tablets taken once daily<br>* Other names: Low dose samidorphan (ALKS 33);Drug: Olanzapine<br>* Tablets taken once daily<br>|
| Experimental: Medium Dose<br>Olanzapine + medium dose samidorphan tablets taken once daily | Drug: Samidorphan (Medium Dose)<br>* Tablets taken once daily<br>* Other names: Medium dose samidorphan (ALKS 33);Drug: Olanzapine<br>* Tablets taken once daily<br>|
| Experimental: High Dose<br>Olanzapine + high dose samidorphan tablets taken once daily | Drug: Samidorphan (High Dose)<br>* Tablets taken once daily<br>* Other names: High dose samidorphan (ALKS 33);Drug: Olanzapine<br>* Tablets taken once daily<br>|
| Placebo Comparator: Placebo<br>Olanzapine + placebo tablets taken once daily | Drug: Placebo<br>* Tablets taken once daily<br>Drug: Olanzapine<br>* Tablets taken once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Total Positive and Negative Syndrome Scale (PANSS) Score | Change from baseline (Day 8) to Day 92 (end of study Part A). The PANSS is a 30-item scale measuring severity of schizophrenia symptoms. Symptom severity for each item is rated on a 7-point scale (1 = absent; 7 = extreme), and the total score is added together, with a minimum score of 30 and a maximum score of 210. A higher score indicates more severe symptoms, while a lower score indicates less severe symptoms. | Baseline (Day 8) to Day 92 (end of study Part A) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Body Weight (Kilogram) From Baseline to Day 92 | Percent change from baseline (Day 8) to the end of Part A (Day 92) | Baseline (Day 8) to Day 92 (end of study Part A) | 
| Absolute Change in Body Weight (kg) From Baseline to Day 92 | Change from randomization (Day 8) to the end of Part A (Week 12; Day 92) | Baseline (Day 8) to Day 92 (end of study Part A) | 
| Percentage of Subjects Exhibiting Significant Weight Gain at Day 92 | Significant weight gain will include a >=5%, >= 7%, or >=10% gain in body weight from baseline (Day 8) to Day 92 (end of study Part A) | Baseline (Day 8) to Day 92 (end of study Part A) | 
| Change in Clinical Global Impressions - Severity (CGI-S) From Baseline to Day 92 | Change in CGI-S score from baseline (Day 8) to the end of Part A (Week 12; Day 92). The CGI-S is a 7-point scale intended to measure the severity of a patient's illness at the time of assessment. Scores range from 1 (normal) to 7(extremely ill), so a higher score is correlative to more severe illness. | Baseline (Day 8) to Day 92 (end of study Part A) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Olanzapine, Samidorphan, Alkermes