Roluperidone + Olanzapine for Schizophrenia

Recruiting at 2 trial locations

Overseen By VP, Program Management

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Minerva Neurosciences

Must not be taking: Proton pump inhibitors

Disqualifiers: Major depressive disorder, Bipolar, Panic, others

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

Compensation: Varies

Number of Visits: 1

17 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing the safety and effectiveness of using two medications, Roluperidone and Olanzapine, together in adults with severe schizophrenia symptoms. The goal is to see if this combination can better improve mood and behavior by affecting brain chemicals.

Will I have to stop taking my current medications?

Yes, participants will need to stop taking their current psychotropic medications before starting the trial. There is a 'washout period' (time without taking certain medications) during the screening phase to ensure safety and eligibility.

What evidence supports the effectiveness of the drug Olanzapine for treating schizophrenia?

Research shows that Olanzapine is effective in reducing symptoms of schizophrenia, with studies indicating it may have a better risk-benefit profile compared to other similar drugs like risperidone. Patients treated with Olanzapine showed significant improvements in symptoms and quality of life measures. ^{1 2 3 4 5}

Is the combination of Roluperidone and Olanzapine safe for treating schizophrenia?

Olanzapine has been shown to be generally safe for treating schizophrenia, with some side effects like drowsiness, weight gain, and mild liver enzyme changes. Serious side effects like seizures and sexual dysfunction are rare. ^{3 6 7 8 9}

How is the drug Roluperidone + Olanzapine unique for treating schizophrenia?

Roluperidone combined with Olanzapine for schizophrenia is unique because it potentially offers a novel approach by combining two different mechanisms of action, which may enhance treatment effectiveness compared to using Olanzapine alone. While Olanzapine is known for its serotonin/dopamine antagonism, the addition of Roluperidone could provide complementary benefits, although specific details about Roluperidone's action are not provided in the available research. ^{3 4 5 10 11}

Eligibility Criteria

Adults with schizophrenia for at least a year, BMI under 35, stable symptoms, and not on conflicting meds can join. They must have moderate to severe negative symptoms but no major depressive or bipolar disorder. Women of childbearing potential need double contraception.

Inclusion Criteria

Discontinued psychotropic medications without risk to their clinical status or safety by Baseline

Female subject, if not of childbearing potential, must be a woman who is post-menopausal or permanently sterilized

Female subject, if of childbearing potential, must test negative for pregnancy and must be using a double barrier contraceptive method

Exclusion Criteria

Positive urine drug screen for drugs of abuse

You have a high score on items 1, 2, or 3, or a very high score on item 4 of a test called the Barnes Akathisia Rating Scale (BARS).

PANSS item score of > 4 on: P4 Excitement/Hyperactivity, P6 Suspiciousness/persecution, P7 Hostility, G8 Uncooperativeness, G14 Poor impulse control

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Inpatient stay

Treatment Phase 1

Roluperidone 64 mg/day administered as monotherapy for 7 days

1 week

Inpatient stay

Treatment Phase 2

Concomitant administration of Olanzapine 10 mg/day and Roluperidone 64 mg/day for 10 days

10 days

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

At least 1 visit (in-person)

Treatment Details

Interventions

• Olanzapine
• Roluperidone

Trial Overview The trial tests Roluperidone alone for a week then combined with Olanzapine for another ten days in adults with schizophrenia. It aims to understand the safety and how these drugs work together when taken by patients.

Participant Groups

Group I: Treatment Phase 2 Experimental Treatment 2 Interventions

Roluperidone 64 mg oral and olanzapine 10 mg oral administered at the same time daily for 10 days on Days 8-17.

Group II: Treatment Phase 1 Experimental Treatment 1 Intervention

Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7.

Who Is Running the Clinical Trial?

Minerva Neurosciences

Lead Sponsor

Trials

6

Recruited

960+

Findings from Research

In a one-year study involving schizophrenic outpatients with prominent negative symptoms, olanzapine was associated with significantly fewer extrapyramidal symptoms (EPS) and sexual adverse events compared to risperidone, indicating better safety and tolerability for olanzapine.

While both medications led to weight gain, olanzapine resulted in a higher percentage of patients experiencing clinically significant weight increases (37.8% vs. 16.8% for risperidone), suggesting that while olanzapine may be safer in terms of EPS and sexual side effects, it may also pose a greater risk for weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and tolerability of olanzapine versus risperidone: a one-year randomized study in outpatients with schizophrenia with prominent negative symptoms]. Ciudad, A., Alvarez, E., Bousoño, M., et al.[2018]

Risperidone and olanzapine, two novel antipsychotics, show improved efficacy and safety compared to conventional antipsychotic medications in treating schizophrenia, based on a synthesis of randomized clinical trials.

Risperidone demonstrated clearer benefits in symptom control compared to olanzapine, and patients on these novel medications were less likely to need additional treatment for extrapyramidal symptoms, indicating a better overall safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical value of risperidone and olanzapine: A meta-analysis of efficacy and safety. Peuskens Marc De Hert Michael Jones, J.[2014]

Olanzapine demonstrated statistically significant improvements in both efficacy and safety compared to risperidone in treating schizophrenia, based on a meta-analysis of randomized, double-blind studies.

The analysis showed that olanzapine was associated with fewer anticholinergic side effects and lower dropout rates, indicating it may enhance patient quality of life and treatment adherence over both short (≤12 weeks) and longer-term (>12 weeks) periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of olanzapine versus risperidone for the treatment of schizophrenia: a meta-analysis of randomised clinical trials. Mudge, MA., Davey, PJ., Coleman, DK., et al.[2014]

In a clinical safety review involving 2500 patients treated with olanzapine for acute schizophrenia, the overall discontinuation rate was low, indicating good tolerability of the medication.

While olanzapine was associated with some significant adverse effects such as somnolence, weight gain, and elevated liver enzymes, it showed minimal risk for parkinsonism, akathisia, and no cases of hematotoxicity, making it a relatively safe option compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of olanzapine. Beasley, CM., Tollefson, GD., Tran, PV.[2018]

References

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

A randomized, 1-year follow-up study of olanzapine and risperidone in the treatment of negative symptoms in outpatients with schizophrenia. [2018]

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

Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. [2022]

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

A comparative effectiveness study of risperidone and olanzapine in the treatment of schizophrenia. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Olanzapine vs risperidone in the management of schizophrenia: a randomized double-blind trial in Australia and New Zealand. [2019]

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

A randomized controlled trial of risperidone and olanzapine for schizophrenic patients with neuroleptic-induced tardive dyskinesia. [2019]

6. Spain pubmed.ncbi.nlm.nih.gov

[Safety and tolerability of olanzapine versus risperidone: a one-year randomized study in outpatients with schizophrenia with prominent negative symptoms]. [2018]

7. England pubmed.ncbi.nlm.nih.gov

The clinical value of risperidone and olanzapine: A meta-analysis of efficacy and safety. [2014]

8. England pubmed.ncbi.nlm.nih.gov

A comparison of olanzapine versus risperidone for the treatment of schizophrenia: a meta-analysis of randomised clinical trials. [2014]

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

Safety of olanzapine. [2018]

10. Pakistan pubmed.ncbi.nlm.nih.gov

Effect of olanzapine combined with risperidone in the treatment of schizophrenia and its influence on cognitive function. [2022]

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

Dosing the antipsychotic medication olanzapine. [2018]