OLZ/SAM vs. Olanzapine for Schizophrenia or Bipolar Disorder

Recruiting at 68 trial locations

Overseen By Lori Penatzer

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Alkermes, Inc.

Must be taking: Antipsychotics

Must not be taking: Opioids, Opioid antagonists

Disqualifiers: Major depressive episode, Seizure disorder, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

220 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new treatment, OLZ/SAM (a combination of olanzapine and samidorphan), affects weight compared to olanzapine in young people with schizophrenia or bipolar disorder. Researchers aim to determine if this combination can manage symptoms with less weight gain. Suitable participants are those aged 10 to 17 with schizophrenia or bipolar I disorder who are currently taking olanzapine or another ineffective antipsychotic. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it seems you can continue if you are currently treated with olanzapine. If you are on another antipsychotic, you may need to switch if it hasn't been effective.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown OLZ/SAM to be safe. Research indicates that the combination of olanzapine and samidorphan is well-tolerated over long periods. Participants taking OLZ/SAM for up to four years generally maintained symptom control without major safety issues.

Reports highlight that OLZ/SAM helps stabilize body weight and has a manageable effect on metabolism, meaning it doesn't significantly disrupt how the body uses energy and nutrients. Overall, safety data for OLZ/SAM remains consistent across different studies, making it a promising option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia or bipolar disorder?

Researchers are excited about OLZ/SAM because it combines olanzapine, a well-known antipsychotic, with samidorphan, an opioid receptor modulator, in one fixed-dose pill. This combination aims to address the common side effect of weight gain associated with olanzapine by potentially mitigating it with samidorphan. Unlike current options that primarily focus on symptom control, OLZ/SAM offers a novel approach by aiming to improve the overall side effect profile, making it a promising alternative for treating schizophrenia and bipolar disorder.

What evidence suggests that this trial's treatments could be effective for schizophrenia or bipolar disorder?

This trial will compare OLZ/SAM, a combination of olanzapine and samidorphan, with olanzapine alone. Research has shown that OLZ/SAM results in significantly less weight gain than olanzapine alone. This finding is important because weight gain is a common side effect of olanzapine. Long-term studies have demonstrated that individuals taking OLZ/SAM maintained stable weight, and their symptoms of schizophrenia or bipolar disorder remained steady for up to four years. The treatment proved to be safe and well-tolerated during this period. Thus, OLZ/SAM can effectively manage symptoms while reducing weight-related issues. ^{2 4 5 6 7}

Who Is on the Research Team?

David McDonnell, MD

Principal Investigator

Alkermes, Inc.

Are You a Good Fit for This Trial?

This trial is for young people aged 10-17 with bipolar I disorder or schizophrenia. They must be diagnosed by DSM-5 criteria, have family support, and can't be a danger to themselves or others. Participants should either be on olanzapine already or not responding well to other antipsychotics.

Inclusion Criteria

I am a teenager diagnosed with schizophrenia or bipolar I disorder.

I can receive treatment without staying in the hospital.

Subject has reliable family/legal guardian support available for outpatient management

Exclusion Criteria

Subject poses a current suicide risk as assessed by the Investigator or as confirmed by the baseline C-SSRS

Subject has participated in a clinical study of an investigational product within the last 30 days prior to Screening

I have received a long-acting injectable antipsychotic within the last 3 injection cycles.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive OLZ/SAM or olanzapine to evaluate weight gain as assessed by change in BMI Z-score

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olanzapine
• OLZ/SAM

Trial Overview The study compares the effect of OLZ/SAM versus olanzapine alone on BMI Z-score in youth with schizophrenia or bipolar I disorder. It aims to see if OLZ/SAM leads to less weight gain than olanzapine, which is known for causing weight increase.

How Is the Trial Designed?

Group I: Group 1 OLZ/SAM Experimental Treatment 1 Intervention

Fixed dose combination of olanzapine and samidorphan

Group II: Group 2 Olanzapine Active Control 1 Intervention

Fixed dose of olanzapine

OLZ/SAM is already approved in United States for the following indications:

Approved in United States as Lybalvi for:

• Schizophrenia
• Bipolar I disorder
• Acute treatment of manic or mixed episodes as monotherapy or adjunctively to lithium or valproate
• Maintenance monotherapy

Who Is Running the Clinical Trial?

Alkermes, Inc.

Lead Sponsor

Trials

118

Recruited

27,200+

Richard Pops

Alkermes, Inc.

Chief Executive Officer since 1991

BA in Economics from Stanford University

Dr. Craig Hopkinson

Alkermes, Inc.

Chief Medical Officer since 2017

MD

Published Research Related to This Trial

In a 52-week study involving 265 patients with schizophrenia, the combination of olanzapine and samidorphan (OLZ/SAM) was found to be well tolerated, with stable weight and waist circumference changes, indicating it may help mitigate weight gain associated with olanzapine.

The treatment also maintained stable schizophrenia symptoms, as shown by consistent Positive and Negative Syndrome Scale (PANSS) scores, with 81.3% of patients reporting mild illness severity by the end of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3, multicenter study to assess the 1-year safety and tolerability of a combination of olanzapine and samidorphan in patients with schizophrenia: Results from the ENLIGHTEN-2 long-term extension. Kahn, RS., Silverman, BL., DiPetrillo, L., et al.[2022]

Olanzapine-samidorphan (OLZ/SAM) is a newly FDA-approved medication that effectively combines the antipsychotic properties of olanzapine with samidorphan to help reduce weight gain associated with olanzapine treatment.

While OLZ/SAM is effective in mitigating weight gain, it does not promote weight loss and has limited effects on metabolic laboratory variables, indicating a need for further research to compare its effectiveness with other weight management strategies in antipsychotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine-samidorphan combination tablets for the treatment of schizophrenia and bipolar I disorder - what is it, and will it be used? Faden, J., Serdenes, R., Citrome, L.[2022]

The olanzapine/samidorphan (OLZ/SAM) combination treatment significantly reduces the risk of clinically significant weight gain (>10%) compared to olanzapine (OLZ) monotherapy in adults with schizophrenia, with an odds ratio of 0.50.

OLZ/SAM maintains similar clinical efficacy to OLZ while improving tolerability, indicating it may be a preferable option for managing schizophrenia without the added risk of significant weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine and samidorphan combination treatment: A systematic review. Jawad, MY., Alnefeesi, Y., Lui, LMW., et al.[2022]

The combination of olanzapine and samidorphan (OLZ/SAM) effectively treats schizophrenia while significantly reducing the weight gain side effects commonly associated with olanzapine alone, based on studies involving approximately 960 patients.

OLZ/SAM has been approved for treating bipolar I disorder and offers advantages such as once-daily dosing and improved tolerability, which may enhance patient adherence to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine/Samidorphan: A New Option for the Treatment of Adults With Schizophrenia or Bipolar I Disorder. Pham, H., Warlick, H., Bermudez, R., et al.[2023]

In a 52-week study involving 281 patients with schizophrenia, the combination of olanzapine and samidorphan (OLZ/SAM) was generally well tolerated, with most patients completing the treatment and showing sustained improvement in schizophrenia symptoms as measured by PANSS and CGI-S scores.

While there was a mean weight increase of 1.86 kg over the year, this change stabilized early in the treatment, suggesting that OLZ/SAM may effectively mitigate the weight gain typically associated with olanzapine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and durability of effect with a combination of olanzapine and samidorphan in patients with schizophrenia: results from a 1-year open-label extension study. Yagoda, S., Graham, C., Simmons, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8437420/

An Evidence-Based Review of OLZ/SAM for Treatment of ... OLZ/SAM treatment resulted in significantly less weight gain versus olanzapine; weight remained stable with long-term treatment.

2. lybalvihcp.com lybalvihcp.com/efficacy-safety

Efficacy & Safety Explore olanzapine efficacy and safety data that provided the basis for the bipolar I disorder indication for LYBALVI.1. See Bipolar I Disorder Data ...

3. investor.alkermes.com investor.alkermes.com/news-releases/news-release-details/alkermes-announces-topline-results-long-term-open-label-safety

Press Releases Patients' symptoms of schizophrenia or bipolar I disorder remained stable with up to four years of treatment with LYBALVI, as measured by the ...

4. psychiatrist.com psychiatrist.com/jcp/long-term-safety-tolerability-treatment-effect-olanzapine-samidorphan-open-label-study/

Long-Term Safety, Tolerability, and Durability of Treatment ... During up to 4 years of treatment, the combination of olanzapine/samidorphan was safe and well-tolerated, and patients' symptoms remained ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/213378s000lbl.pdf

LYBALVI (olanzapine and samidorphan) - accessdata.fda.gov Bipolar I Disorder. The efficacy of LYBALVI in the treatment of adult patients with bipolar I disorder has been established based on adequate and well ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39630083/

Long-Term Safety, Tolerability, and Durability of Treatment ... Conclusion: OLZ/SAM maintained symptom control with a long-term safety profile over 4 years consistent with that of prior studies. Trials ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04987229

Long-term Safety Extension Study of OLZ/SAM in Pediatric ... Individual Patients: Allows a single patient, with a serious disease or condition who cannot participate in a clinical trial, access to a drug or biological ...