Study to Evaluate Weight Gain as Assessed by Change in BMI Z-score in Pediatric Subjects With Schizophrenia or Bipolar I Disorder

Study Overview
=================
Brief Summary
-----------------
To compare changes in body mass index (BMI) Z-score following treatment with OLZ/SAM vs olanzapine

Official Title
-----------------
A Phase 3, Randomized, Double-Blind, 52-Week Study of OLZ/SAM vs Olanzapine to Evaluate Weight Gain as Assessed by Change in BMI Z-Score in Pediatric Subjects With Schizophrenia or Bipolar I Disorder (ENLIGHTEN-Youth)

Conditions
-----------------
Schizophrenia, Bipolar I Disorder

Intervention / Treatment
-----------------
* Drug: OLZ/SAM
* Drug: Olanzapine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects aged 13 to 17 years with schizophrenia or aged 10 to 17 years with bipolar I disorder, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria Subject is an outpatient or will be able to be treated on an outpatient basis (per Investigator judgement) by study Week 2 Subject has reliable family/legal guardian support available for outpatient management Subject is either currently treated with olanzapine, or if treated with another antipsychotic, the subject has had an inadequate response (eg, unsatisfactory clinical response, AEs, or nonadherence to current medication) based on Investigator judgment Subject must not be a danger to self or others (per Investigator judgement) Exclusion Criteria: Subject presents with a major depressive episode(bipolar I disorder) or other neuropsychiatric diagnosis (according to DSM-5 criteria) including schizoaffective disorder, current major depressive disorder that is untreated and/or unstable, or any other psychiatric condition that could interfere with participation in the study Subject has a history of seizure disorder (exception: history of febrile seizures), severe head trauma with loss of consciousness within the 12 months prior to Screening, or other clinically significant neurological condition within the 12 months prior to Screening Subject poses a current suicide risk as assessed by the Investigator or as confirmed by the baseline Columbia-Suicide Severity Rating Scale (C-SSRS) Subject has received olanzapine for >= 14 days during the month prior to screening, or has a history of poor or inadequate response to treatment with olanzapine Subject has taken opioid agonists within 14 days prior to Screening, or within 30 days prior to Screening (for long-acting opioid agonists) Subject anticipates needing to take opioid medication during the study period (eg, planned surgery, including oral surgery) Subject has taken opioid antagonists including naltrexone (any formulation) or naloxone within 60 days prior to Screening Subject has used a long-acting injectable antipsychotic medication within 3 injection cycles prior to Screening Subject has a BMI percentile >98th or <5th Subject has a diagnosis of diabetes mellitus or presents with prediabetes lab results at Screening (hemoglobin A1c [HbA1c] >= 6%) Subject has started a smoking cessation program within the 6 months prior to Screening or has joined a weight management program or has had significant changes in diet or exercise regimen within 6 weeks prior to Screening Subject has participated in a clinical study of an investigational product within the last 30 days prior to Screening

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 OLZ/SAM<br>Fixed dose combination of olanzapine and samidorphan | Drug: OLZ/SAM<br>* OLZ/SAM refers to the fixed dose combination of olanzapine and samidorphan. The starting dose of olanzapine will be 2.5 mg/day or 5 mg/day at the discretion of the Investigator with a maximum daily dose of 20mg/day. The starting dose of samidorphan will be 5 or 10 mg.<br>* Other names: ALKS 3831, LYBALVI;|
| Active Comparator: Group 2 Olanzapine<br>Fixed dose of olanzapine | Drug: Olanzapine<br>* The starting dose of olanzapine will be 2.5 mg/day or 5 mg/day at the discretion of the Investigator with a maximum daily dose of 20mg/day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in body mass index (BMI) Zscore at week 12 | To compare changes in body mass index (BMI) Z-score following treatment with OLZ/SAM vs olanzapine | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with >=0.5 increase in BMI Z-score at Week 12 | To compare subjects with clinical significant BMI Z-score increase with OLZ/SAM vs olanzapine | 12 weeks | 
| Time to all-cause discontinuation of study drug over 52 weeks | To compare time to all-cause discontinuation of study drug with OLZ/SAM vs olanzapine | Up to 52 weeks | 
| Change from baseline in waist circumference | To compare the change from baseline in waist circumference with OLZ/SAM vs olanzapine | 12 weeks | 
| Change from baseline in Positive and Negative Syndrome Scale (PANSS) total score for patients with schizophrenia by visit | To compare the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score with OLZ/SAM vs olanzapine for patients with schizophrenia | 12 weeks | 
| Change from baseline in Young Mania Rating Scale (YMRS) in patients with Bipolar I disorder | To compare the change from baseline in YMRS with OLZ/SAM vs olanzapine for patients with bipolar I disorder | 12 weeks | 
| Change from baseline in Children's Depression Rating Scale-Revised (CDRS-R) for patients with bipolar I disorder by visit | To compare the change from baseline in CDRS-R with OLZ/SAM vs olanzapine for patients with bipolar I disorder | 12 weeks | 
| Incidence of Adverse Events |  | Up to 52 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
LYBALVI, Schizophrenia, Bipolar I Disorder, Pediatric, Olanzapine, Samidorphan