OLZ/SAM for Schizophrenia

Enrolling by invitation at 65 trial locations

Overseen By Senior Director, Global Clinical Services

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Alkermes, Inc.

Must be taking: OLZ/SAM

Must not be taking: Opioids, Olanzapine interactions

Disqualifiers: Suicide risk, Pregnancy, 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: Long-term

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the long-term safety and comfort of OLZ/SAM (Olanzapine/Samidorphan) for young people with schizophrenia or Bipolar I disorder. Participants will continue their OLZ/SAM treatment based on previous dosing. The trial seeks individuals who participated in specific earlier studies and could benefit from ongoing treatment. Those needing continued outpatient care with family support may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to the potential availability of this treatment.

Do I have to stop taking my current medications for the trial?

You may need to stop taking your current medications if they interact with olanzapine, which is part of the trial treatment. It's best to discuss this with the trial team to see if your medications are affected.

Is there any evidence suggesting that OLZ/SAM is likely to be safe for humans?

Research has shown that OLZ/SAM, a combination of olanzapine and samidorphan, has undergone long-term safety testing, with some studies lasting up to four years. These studies found that OLZ/SAM is generally safe and well-tolerated. Most participants did not experience serious side effects, although some reported changes in body weight.

For those considering joining a trial, it's important to know that OLZ/SAM has a stable metabolic profile, typically not causing major metabolic changes. While some side effects exist, research suggests OLZ/SAM is safe for many people over extended periods. Prospective participants should consult a healthcare provider about potential side effects. ^{1 2 3 4 5}

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

Researchers are excited about OLZ/SAM for schizophrenia because it combines olanzapine with samidorphan. Olanzapine is a well-known antipsychotic, but it often leads to weight gain, a major side effect. Samidorphan is an opioid receptor antagonist that may help mitigate this weight gain. This combination could provide the benefits of olanzapine while reducing one of its most challenging side effects, offering a potentially improved treatment option for individuals with schizophrenia.

What evidence suggests that OLZ/SAM might be an effective treatment for schizophrenia?

Research has shown that OLZ/SAM, a combination of olanzapine and samidorphan, effectively manages schizophrenia symptoms. Studies have found that people using OLZ/SAM maintain stable symptoms over time. Adding samidorphan reduces the weight gain often caused by olanzapine alone, making the treatment more manageable. Long-term evidence supports that this combination controls schizophrenia symptoms and is safe for extended use. This makes OLZ/SAM a promising choice for treating schizophrenia and bipolar I disorder. ^{2 3 4 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 kids with schizophrenia or Bipolar I disorder who finished a previous study (ALKS 3831-A311/A312) or left it due to weight gain. They mustn't be at risk of harm, have family support, agree to follow birth control rules, and can benefit from continued OLZ/SAM treatment.

Inclusion Criteria

It is determined by the doctor that you will benefit from continuing treatment with OLZ/SAM medication.

Subject must not be a danger to self or others (per Investigator judgement) and has family support available to be maintained as an outpatient.

Subject has completed the treatment period in either the ALKS 3831-A311 or the ALKS 3831-A312 study within 10 days of enrolling into this extension study, or subject had terminated early from Study ALKS 3831-A312 due to the clinically significant weight gain criterion.

Exclusion Criteria

Subject has a positive test for opioids.

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 since the last visit.

I am not on medications that can't be taken with olanzapine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive OLZ/SAM at a dose determined by the Investigator

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• OLZ/SAM

Trial Overview The trial tests the long-term safety of a medication combo called OLZ/SAM in young patients. It's an extension study for those who've been part of prior research on this treatment and aims to see how they do over more time.

How Is the Trial Designed?

Group I: All subjects Experimental Treatment 1 Intervention

All subjects will receive OLZ/SAM at a dose determined by the Investigator and based on the olanzapine dosing received in the antecedent study (ALKS 3831-A311 or ALKS 3831-A312 ENLIGHTEN-Youth)

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]

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]

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]

Citations

1. lybalvihcp.com lybalvihcp.com/efficacy-safety

Efficacy & Safety ENLIGHTEN-1 efficacy and safety data. Explore pivotal trial data demonstrating the efficacy and safety of LYBALVI in schizophrenia.1. See ENLIGHTEN-1 Data ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32160422/

Olanzapine Plus Samidorphan (ALKS 3831) in ... OLZ/SAM was not superior to olanzapine in the time to EEDS and was well tolerated in patients with schizophrenia and AUD.

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 ... Results: Of 524 patients enrolled, 523 received ≥1 dose of OLZ/SAM. Of these, 460 (88%) patients had schizophrenia, 15 (3%) had schizophreniform ...

5. pharmacytimes.com pharmacytimes.com/view/long-term-data-on-olanzapine-and-samidorphan-highlight-maintained-schizophrenia-symptom-control

Long-Term Data On Olanzapine and Samidorphan ... The addition of samidorphan can support the antipsychotic efficacy of olanzapine while mitigating associated weight gain.

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

Long-Term Safety, Tolerability, and Durability of Treatment ... Mean (SD) OLZ/SAM exposure was 652.4 (454.8) days. Of 451 patients eligible for 2 years of treatment, 242 (53.7%) received it; of 335 patients ...

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

Long-term Safety Extension Study of OLZ/SAM in Pediatric ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...