Roluperidone + Olanzapine for Schizophrenia

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of combining Roluperidone and Olanzapine to treat negative symptoms of schizophrenia. The goal is to determine how these drugs work together and their safety when used simultaneously, potentially aiding doctors in future prescriptions. Individuals with schizophrenia for at least a year and stable symptoms might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that roluperidone, when used alone, produces promising results. Studies found that it improved symptoms in people with schizophrenia and was generally well-tolerated, with most patients not experiencing serious side effects.

Olanzapine, in contrast, is already a well-known medication for schizophrenia. While effective, it can cause side effects such as weight gain and drowsiness.

Currently, little information exists on the safety of using roluperidone and olanzapine together. As this trial begins, it will provide insights into the safety and tolerability of this combination for patients. The trial aims to determine whether using them together is safe for treating negative symptoms of schizophrenia. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Roluperidone for schizophrenia because it offers a fresh approach by targeting the sigma-2 receptor complex, which is different from most current treatments that often focus on dopamine receptors. This unique mechanism of action could mean fewer side effects compared to traditional antipsychotics like olanzapine or risperidone. Additionally, Roluperidone is being studied in combination with olanzapine, which may offer enhanced effectiveness by addressing symptoms through multiple pathways. This combination approach is particularly promising for potentially improving outcomes for patients who don't fully respond to existing medications.

What evidence suggests that this trial's treatments could be effective for schizophrenia?

Research has shown that roluperidone alone, which participants may receive during the initial phase of this trial, can help reduce negative symptoms of schizophrenia, such as lack of motivation and social withdrawal. Studies have also found that it can improve daily life for people with these symptoms. In the subsequent phase, participants will receive a combination of roluperidone and olanzapine. Although there is less information on using roluperidone with olanzapine, olanzapine is a well-known medication that helps manage schizophrenia symptoms. Combining roluperidone and olanzapine might enhance treatment by addressing both negative symptoms and overall management of schizophrenia. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35211743/

Efficacy and Safety of Roluperidone for the Treatment ... Conclusions: Results of this trial confirm the potential of roluperidone as a treatment of negative symptoms and improving everyday functioning ...

2. ir.minervaneurosciences.com ir.minervaneurosciences.com/news-releases/news-release-details/minerva-neurosciences-announces-results-phase-3-trial-0

Minerva Neurosciences Announces the Results of ... Roluperidone, administered without concomitant treatment with antipsychotics, can potentially improve negative symptoms of schizophrenia and social functioning ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924977X24001603

Network intervention analysis indicates that roluperidone ... Network intervention analysis indicates that roluperidone achieves its effect on negative symptoms of schizophrenia by targeting avolition · Experimental ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03397134

NCT03397134 | Study to Evaluate Efficacy and Safety of ... The primary objective is to evaluate the efficacy of 2 fixed doses of roluperidone compared to placebo in improving the negative symptoms of ...

5. academic.oup.com academic.oup.com/ijnp/article/28/6/pyaf032/8138412

Roluperidone monotherapy, a treatment for negative ... During the open label 6 or 9 months of roluperidone treatment, negative symptoms and social functioning continue to improve14 and the rate of psychotic ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0920996423001226

Long-term effects of Roluperidone on negative symptoms ... In 2 randomized controlled trials (RCT), treatment improved negative symptoms of schizophrenia and social functioning among patients with moderate to severe ...