Olanzapine-samidorphan + Exercise for Bipolar Disorder

Overseen By Megan Mayer, BA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: New York State Psychiatric Institute

Must be taking: Antipsychotics

Must not be taking: Opioids, Opioid antagonists

Disqualifiers: Substance use disorder, Diabetes, Neurological conditions, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain medications like opioid agonists or antagonists before and during the study. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug Olanzapine-samidorphan for treating bipolar disorder?

Research shows that the combination of olanzapine and samidorphan is effective for treating schizophrenia and bipolar I disorder, while also helping to reduce weight gain, a common side effect of olanzapine. ^{1 2 3 4 5}

Is the combination of olanzapine and samidorphan safe for humans?

The combination of olanzapine and samidorphan has been studied for safety in people with schizophrenia and bipolar I disorder. It is designed to reduce weight gain associated with olanzapine, and long-term studies have shown it to be generally safe and well-tolerated. ^{1 2 3 4 5}

How is the drug olanzapine-samidorphan unique for treating bipolar disorder?

Olanzapine-samidorphan is unique because it combines olanzapine, which is effective for treating bipolar disorder, with samidorphan, which helps reduce the weight gain often caused by olanzapine. This combination aims to provide the benefits of olanzapine while minimizing its common side effect of weight gain. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a single site trial in 30 patients with schizophrenia, schizoaffective, or bipolar I/II/NOS disorder in which all participants will receive eight weeks of olanzapine and samidorphan (Olz/Sam) plus four weeks of aerobic exercise.

Eligibility Criteria

This trial is for individuals with schizophrenia, schizoaffective disorder, or bipolar I/II/NOS. Participants will engage in an 8-week treatment with Olanzapine-samidorphan (Olz/Sam) combined with a 4-week aerobic exercise program.

Inclusion Criteria

Body Mass Index (BMI) of 18.0-40.0 kg/m2 at Visits 1 and 2

Willing to provide informed consent at Visit 1

I have been diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder.

Exclusion Criteria

I do not have any health conditions that could worsen with study treatment.

I have a bowel condition that has caused me to lose weight.

Positive drug screen for opioids, phencyclidine, amphetamine/methamphetamine, or cocaine at Visit 1 or Visit 2

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 8 weeks of open label Olz/Sam, with 4 weeks of aerobic exercise

8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Olanzapine-samidorphan

Trial Overview The study tests the combination of Olz/Sam medication and aerobic exercise to see how they work together in treating patients with certain psychiatric disorders over a period of eight weeks at a single site.

Participant Groups

Group I: olanzapine-samidorphan plus exercise Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

Findings from Research

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Effects of Olanzapine Combined With Samidorphan on Weight Gain in Schizophrenia: A 24-Week Phase 3 Study. [2021]

3. 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]

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]