OLZ/SAM for Schizophrenia

Recruiting at 59 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

236 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial evaluates the safety and tolerability of OLZ/SAM in children and adolescents with schizophrenia or Bipolar I disorder. OLZ/SAM combines olanzapine to manage symptoms and samidorphan to reduce weight gain. Olanzapine is a well-established antipsychotic effective for schizophrenia and bipolar I disorder, but its use is limited by significant weight gain; samidorphan is added to mitigate this side effect.

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.

What data supports the effectiveness of the drug OLZ/SAM for treating schizophrenia?

Research shows that OLZ/SAM, a combination of olanzapine and samidorphan, maintains the strong antipsychotic effects of olanzapine while reducing weight gain, a common side effect. Studies have demonstrated its safety and effectiveness over a year in patients with schizophrenia. ^{1 2 3 4 5}

Is OLZ/SAM safe for humans?

OLZ/SAM, also known as Lybalvi, has been studied for its safety in treating schizophrenia and bipolar I disorder. Research shows it aims to reduce weight gain associated with olanzapine while maintaining its effectiveness, and long-term studies have assessed its safety and tolerability over a year. ^{1 2 4 5 6}

What makes the drug OLZ/SAM unique for treating schizophrenia?

OLZ/SAM is unique because it combines olanzapine, a powerful antipsychotic, with samidorphan, which helps reduce the weight gain often caused by olanzapine, making it a more tolerable option for patients. ^{1 2 4 6 7}

Research Team

David McDonnell, MD

Principal Investigator

Alkermes, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. England 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? [2022]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Short-term Safety of ALKS 3831, a Fixed-dose Combination of Olanzapine and Samidorphan, in Adult Subjects with Schizophrenia. [2019]

4. Netherlands 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of a Combination of Olanzapine and Samidorphan in Adult Patients With an Acute Exacerbation of Schizophrenia: Outcomes From the Randomized, Phase 3 ENLIGHTEN-1 Study. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Olanzapine/Samidorphan: A New Option for the Treatment of Adults With Schizophrenia or Bipolar I Disorder. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Olanzapine and samidorphan combination treatment: A systematic review. [2022]