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

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)

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

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Bipolar I Disorder
• Intervention / Treatment: Drug: OLZ/SAM; Drug: Olanzapine

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Global Clinical Services; Phone Number: 888-235-8008 (US Only); Email: clinicaltrials@alkermes.com
• Study Contact Backup: Name: Global Clinical Services; Phone Number: 1-571-599-2702 (Global); Email: clinicaltrials@alkermes.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1133AAH
    • Recruiting
    • Alkermes Investigator Site
  • Córdoba, Argentina, X5003DCE
    • Recruiting
    • Alkermes Investigator Site
  • Mendoza, Argentina, 5500
    • Recruiting
    • Alkermes Investigator Site
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, 1900
      • Recruiting
      • Alkermes Investigator Site
    • La Plata, Buenos Aires, Argentina, C1199ABB
      • Recruiting
      • Alkermes Investigator Site
• Brazil
  • Goiânia, Brazil, 74093-040
    • Recruiting
    • Alkermes Investigator Site
  • Rio de Janeiro, Brazil, 22270-060
    • Recruiting
    • Alkermes Investigator Site
  • São Paulo, Brazil, 05403-010
    • Recruiting
    • Alkermes Investigator Site
  • São Paulo, Brazil, 01228-000
    • Recruiting
    • Alkermes Investigator Site
  • Ceará
    • Fortaleza, Ceará, Brazil, 60430-140
      • Recruiting
      • Alkermes Investigator Site
  • Paraná
    • Curitiba, Paraná, Brazil, 80240-280
      • Recruiting
      • Alkermes Investigator Site
• Colombia
  • Barranquilla, Colombia, 110121
    • Recruiting
    • Alkermes Investigator Site
  • Bello, Colombia, 51053
    • Recruiting
    • Alkermes Investigator Site
  • Bogotá, Colombia, 111166
    • Recruiting
    • Alkermes Investigator Site
  • Bogotá, Colombia, 80020
    • Recruiting
    • Alkermes Investigator Site
  • Pereira, Colombia, 660003
    • Recruiting
    • Alkermes Investigator Site
• Mexico
  • Culiacán, Mexico, 80230
    • Recruiting
    • Alkermes Investigator Site
  • Estado de México, Mexico, C.P. 07000
    • Recruiting
    • Alkermes Investigator Site
  • León, Mexico, 37000
    • Recruiting
    • Alkermes Investigator Site
  • Monterrey, Mexico, 64620
    • Recruiting
    • Alkermes Investigator Site
  • Monterrey, Mexico, 64710
    • Recruiting
    • Alkermes Investigator Site
• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Recruiting
      • Alkermes Investigator Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Recruiting
      • Alkermes Investigator Site
  • California
    • Encino, California, United States, 91316
      • Withdrawn
      • Alkermes Investigator Site
    • Stanford, California, United States, 94305
      • Recruiting
      • Alkermes Investigator Site
    • Upland, California, United States, 91786
      • Withdrawn
      • Alkermes Investigator Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • Withdrawn
      • Alkermes Investigator Site
    • Denver, Colorado, United States, 80202
      • Active, not recruiting
      • Alkermes Investigator Site
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Withdrawn
      • Alkermes Investigator Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • Alkermes Investigator Site
  • Florida
    • Miami, Florida, United States, 33155
      • Withdrawn
      • Alkermes Investigator Site
    • Miami Lakes, Florida, United States, 33016
      • Recruiting
      • Alkermes Investigator Site
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Recruiting
      • Alkermes Investigator Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Alkermes Investigator Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Alkermes Investigator Site
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • Recruiting
      • Alkermes Investigator Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Recruiting
      • Alkermes Investigator Site
    • Omaha, Nebraska, United States, 68198
      • Withdrawn
      • Alkermes Investigator Site
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • Withdrawn
      • Alkermes Investigator Site
  • New York
    • New York, New York, United States, 10016
      • Not yet recruiting
      • Alkermes Investigator Site
  • North Carolina
    • Kinston, North Carolina, United States, 28504
      • Withdrawn
      • Alkermes Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • Alkermes Investigator Site
    • West Chester, Ohio, United States, 45069
      • Recruiting
      • Alkermes Investigator Site
  • Texas
    • DeSoto, Texas, United States, 75115
      • Terminated
      • Alkermes Investigator Site
    • Fort Worth, Texas, United States, 76104
      • Withdrawn
      • Alkermes Investigator Site
  • Virginia
    • Richmond, Virginia, United States, 23220
      • Recruiting
      • Alkermes Investigational Site
  • Washington
    • Everett, Washington, United States, 98201
      • Recruiting
      • Alkermes Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 OLZ/SAM; Fixed dose combination of olanzapine and samidorphan	Drug: OLZ/SAM; 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.; Other Names: ALKS 3831, LYBALVI
Active Comparator: Group 2 Olanzapine; Fixed dose of olanzapine	Drug: Olanzapine; 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

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

Collaborators and Investigators

• Sponsor: Alkermes, Inc.
• Investigators: Study Director: David McDonnell, MD, Alkermes, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: March 22, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Schizophrenia; Pediatric; Bipolar I Disorder; Samidorphan; Olanzapine; LYBALVI
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Olanzapine; lybalvi
• Other Study ID Numbers: ALKS 3831-A312

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No