Phase 1 Study of OLZ/SAM in Pediatric Subjects With Bipolar I Disorder

Study Overview
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Brief Summary
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To evaluate the safety, tolerability, and pharmacokinetics of olanzapine and samidorphan in clinically stable pediatric subjects (10 to 12 years old) with Bipolar I disorder following oral administration of multiple ascending doses of OLZ/SAM

Official Title
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A Phase 1, Multiple-dose, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of OLZ/SAM in Pediatric Subjects (10-12 Years Old) With Bipolar I Disorder

Conditions
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Bipolar I Disorder

Intervention / Treatment
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* Drug: OLZ/SAM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's parent(s)/legal guardian(s) is considered reliable by the Investigator and has agreed to provide support to the subject to ensure compliance with study treatment, visits, and protocol procedures. Male and female subjects between 10 and 12 years of age, inclusive. Subject weighs ≥70 pounds. Subjects who are receiving antipsychotic treatment for their medical condition, with a diagnosis of bipolar I disorder. Subjects must be considered stable, per investigator judgement. Subject is willing to abide by the contraception requirements for the duration of the study. Exclusion Criteria: Subject has a comorbid neuropsychiatric disorder that could interfere with participation in the study. Subject poses a current suicide risk as assessed by the Investigator or as confirmed by the baseline Columbia-Suicide Severity Rating Scale by a response of Yes to question numbers 4 or 5 with ideation or suicidal behavior occurring in the past 12 months (assessed at Screening and at Visit 2, Day 1). Subject has a diagnosis of diabetes or presents with pre-diabetes lab results (hemoglobin A1c ≥6%). Subject has a history of use of clozapine or use of long-acting injectable antipsychotic medication within 3 months prior to Screening. Subject has a DSM-5 (Diagnostic and Statistical Manual of Mental Disorders-5) diagnosis of moderate to severe alcohol disorder, or moderate to severe substance use disorder, within the 3 months prior to Screening. Subject has taken opioid agonists within the 14 days prior to Screening, or has taken long-acting opioid agonist within the 30 days prior to Screening, or has anticipated a need to take opioid medication during the study period (eg, planned surgery, including oral surgery), or has taken opioid antagonists including naltrexone (any formulation) and naloxone within 60 days prior to Screening. Subject is unable to swallow oral medications, as assessed by the Investigator. Subject has a positive urine drug screen for opioids (assessed at Screening and at Visit 2, Day 1). Subject has a positive cotinine test (assessed at Screening and at Visit 2, Day 1). Subject has an intellectual disability, as assessed by the Investigator. Subject has a history of intolerance or hypersensitivity to olanzapine or opioid antagonists, or any component of the study drug.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 12 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 Olanzapine/ 5 mg Samidorphan<br>Olanzapine will be gradually increased to a target dose of 10mg/samidorphan 5mg (Range: 5-20mg Olanzapine/samidorphan 5mg) | Drug: OLZ/SAM<br>* Olanzapine and Samidorphan taken once daily over a max period of 21 days<br>* Other names: ALKS 3831;|
| Experimental: Group 2 Olanzapine/ 10mg Samidorphan<br>Olanzapine will be gradually increased to a target dose of 10mg/samidorphan 10mg (Range: 5-20mg Olanzapine/samidorphan 10mg) | Drug: OLZ/SAM<br>* Olanzapine and Samidorphan taken once daily over a max period of 21 days<br>* Other names: ALKS 3831;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration observed |  | Up to 3 weeks | 
| Area under the plasma concentration-time curve over the 24-hour dosing interval |  | Up to 3 weeks | 
| Time to reach maximum concentration |  | Up to 3 weeks | 
| Incidence of Adverse Events |  | Up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar I Disorder, Olanzapine, Samidorphan, OLZ/SAM, ALKS 3831, Pediatric pharmacokentics, LYBALVI