OLZ/SAM vs. Olanzapine for Schizophrenia or Bipolar Disorder

Recruiting at 61 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

Trial Summary

What is the purpose of this trial?

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

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.

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

Research shows that OLZ/SAM combines the effectiveness of olanzapine, a strong antipsychotic, with samidorphan to reduce weight gain, a common side effect of olanzapine, making it a promising option for treating schizophrenia and bipolar I disorder. ^{1 2 3 4 5}

Is OLZ/SAM safe for humans?

OLZ/SAM, a combination of olanzapine and samidorphan, has been studied for its safety in humans, particularly for 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 3 4 5}

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

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 long-term use. ^{1 2 3 4 5}

Research Team

David McDonnell, MD

Principal Investigator

Alkermes, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. 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]

2. 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]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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