Brilaroxazine for Schizophrenia

(RECOVER Trial)

Recruiting at 16 trial locations

Overseen By Malti Vidhale

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Reviva Pharmaceuticals

Must not be taking: Antipsychotics, MAO inhibitors

Disqualifiers: Substance use disorder, Dementia, others

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

Compensation: Varies

Number of Visits: 4

690 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of Brilaroxazine, a medication for treating acute schizophrenia. Participants will receive either the medication at varying doses or a placebo (a substance with no active drug) to compare outcomes over different durations. The study seeks individuals diagnosed with schizophrenia who have not shown resistance to previous treatments. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Do I have to stop taking my current medications for the trial?

Yes, you will need to stop taking certain medications. You cannot be on antipsychotics during the screening period (at least 3 days before the trial starts) and throughout the study. You also need to stop taking monoamine oxidase inhibitors, CNS stimulants, and certain enzyme-inducing or inhibiting drugs 28 days before the trial begins.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, including antipsychotics, monoamine oxidase inhibitors, and some other specific drugs. You must not be on antipsychotics for at least 3 days before the trial and avoid certain other medications for 28 days prior.

Is there any evidence suggesting that Brilaroxazine is likely to be safe for humans?

Research has shown that Brilaroxazine is generally safe for people with schizophrenia. In one study, it proved effective over a year with few side effects. Most participants did not experience major side effects, and weight gain was minimal. Another study found that only 8.5% of participants discontinued use due to side effects. These results suggest that Brilaroxazine is relatively safe for those with acute schizophrenia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Brilaroxazine is unique because it targets neurotransmitter systems differently than typical antipsychotic medications used for schizophrenia, such as dopamine antagonists. While most treatments focus primarily on dopamine pathways, Brilaroxazine acts on serotonin, dopamine, and other neurotransmitter receptors, potentially offering a broader therapeutic effect. Researchers are excited about Brilaroxazine because it may provide improved symptom relief with fewer side effects compared to current options, like atypical antipsychotics, which often come with weight gain and metabolic issues. This novel mechanism gives hope for a more effective and tolerable treatment for individuals with schizophrenia.

What evidence suggests that Brilaroxazine might be an effective treatment for schizophrenia?

Research has shown that brilaroxazine offers promising results for treating schizophrenia. In earlier studies, it helped alleviate a wide range of symptoms over an extended period. Most participants tolerated the treatment well, with few discontinuing due to side effects, even at the higher dose of 50 mg. In this trial, participants may receive either a placebo or brilaroxazine at doses of 15 mg or 50 mg once daily. These findings suggest that brilaroxazine could be an effective option for managing acute schizophrenia. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Reviva Pharma

Are You a Good Fit for This Trial?

Adults aged 18-65 with acute schizophrenia can join this trial. They must understand and sign a consent form, have not used certain antipsychotics recently or drugs that strongly affect the body's enzyme systems, and cannot have treatment-resistant schizophrenia, history of clozapine use, substance abuse disorders within the last six months, brain injuries affecting cognition, dementia or other CNS diseases.

Inclusion Criteria

I have been diagnosed with schizophrenia.

Subject reads, understands, and signs an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved current ICF prior to performing any of the Screening procedures

Exclusion Criteria

Positive Urine Drug Screen for drugs of abuse, including amphetamines, barbiturates, cocaine, ecstasy, phencyclidine or opiates meeting criteria of moderate-to-severe DSM-5 substance use disorder.

Meets criteria for moderate-to-severe substance use disorder within past 6 months prior to Screening (excluding those related to caffeine or nicotine)

I have a psychotic disorder not including schizophrenia, or behavior issues from substance abuse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive Brilaroxazine or placebo at fixed doses of 15 mg or 50 mg once daily for 28 days

4 weeks

4 visits (in-person)

Open-label Extension

Participants receive Brilaroxazine at flexible doses of 15-50 mg once daily for 52 weeks

52 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brilaroxazine

Trial Overview The study tests Brilaroxazine's safety and effectiveness against a placebo in treating acute schizophrenia. Participants will receive either 15 mg or 50 mg daily for one month followed by flexible dosing up to 52 weeks to see how well it works short-term and long-term.

How Is the Trial Designed?

Group I: RP5063 15 mg once daily Active Control 1 Intervention

administered OD for 28 days then flexibly 15-50mg over a period of 52 weeks.

Group II: RP5063 (brilaroxazine) 50 mg once daily Active Control 1 Intervention

administered OD for 28 days, then flexibly 15-50mg over a period of 52 weeks

Group III: Placebo Placebo Group 1 Intervention

administered OD for 28 days.

Who Is Running the Clinical Trial?

Reviva Pharmaceuticals

Lead Sponsor

Trials

3

Recruited

940+

Published Research Related to This Trial

RP5063, a new medication for schizophrenia, shows a clear and predictable pharmacokinetic profile, with a half-life of 40 to 71 hours, making it suitable for once-daily oral administration.

In studies involving healthy volunteers and patients with stable schizophrenia, RP5063 demonstrated linear dose proportionality and was well-absorbed, especially when taken with food, supporting its potential for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of RP5063 Following Single Doses to Normal Healthy Volunteers and Multiple Doses Over 10 Days to Stable Schizophrenic Patients. Cantillon, M., Ings, R., Bhat, L.[2019]

Brexpiprazole is an effective treatment for schizophrenia with a favorable side effect profile, showing minimal extrapyramidal symptoms and metabolic side effects, as well as no significant sedation or QTc prolongation.

The drug requires limited dose titration upon initiation, making it easier to start treatment compared to other antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Brexpiprazole for treatment of schizophrenia: a critical literature study]. Spoelstra, SK., Baas, CAJ., Knegtering, H.[2021]

Brexpiprazole is an effective new treatment for schizophrenia when used alone, providing a novel option for patients managing this condition.

Additionally, brexpiprazole can be used as an adjunctive therapy for major depressive disorder, enhancing the effectiveness of other treatments for individuals with this mental health issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole (Rexulti): A New Monotherapy for Schizophrenia and Adjunctive Therapy for Major Depressive Disorder. Eaves, S., Rey, JA.[2022]

Brexpiprazole, a newly approved antipsychotic, shows a favorable pharmacological profile for treating schizophrenia and major depressive disorder, with a low risk of common side effects like weight gain and extrapyramidal symptoms.

In clinical trials (VECTOR and BEACON), brexpiprazole demonstrated efficacy as a standalone treatment for schizophrenia and as an adjunct therapy for major depressive disorder, improving cognitive performance and sleep patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole: so far so good. Das, S., Barnwal, P., Winston A, B., et al.[2020]

Brexpiprazole, a new antipsychotic approved in 2015, has shown significant improvement in psychotic symptoms for schizophrenia patients, particularly at higher doses (2-4 mg daily), based on clinical trials using the Positive and Negative Syndrome Scale (PANSS).

While brexpiprazole is effective in treating acute schizophrenia, it did not demonstrate benefits for cognitive function in short-term trials, and common side effects included insomnia, akathisia, headache, and agitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole for the treatment of schizophrenia. Hsu, WY., Lane, HY., Lin, CH.[2018]

Brexpiprazole at doses of 2 mg and 4 mg significantly reduced symptoms of acute schizophrenia compared to placebo, as measured by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions Scale (CGI) after 6 weeks.

The treatment was generally well-tolerated, with akathisia being the most common side effect, and only moderate weight gain observed, indicating that brexpiprazole is a viable option for managing acute schizophrenia exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Brexpiprazole for the Treatment of Acute Schizophrenia: A 6-Week Randomized, Double-Blind, Placebo-Controlled Trial. Correll, CU., Skuban, A., Ouyang, J., et al.[2022]

Brexpiprazole is effective for treating schizophrenia, with a response rate of 45.5% compared to 31.0% for placebo, and a number needed to treat (NNT) of 7, indicating it is a beneficial option for patients.

It is also well tolerated, with lower discontinuation rates due to adverse events compared to placebo, and while akathisia was the most common side effect, its occurrence was not significantly higher than in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Citrome, L.[2022]

Brexpiprazole has been shown to significantly improve symptoms of schizophrenia in short-term studies, with a clinically meaningful reduction in the Positive and Negative Syndrome Scale (PANSS) total score, indicating its efficacy as a treatment option.

The medication also demonstrated a favorable safety profile, with minimal side effects and no significant safety concerns, making it a viable long-term maintenance therapy for adults with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole in patients with schizophrenia: overview of short- and long-term phase 3 controlled studies. Marder, SR., Hakala, MJ., Josiassen, MK., et al.[2018]

Brexpiprazole, an atypical antipsychotic, has been shown to significantly improve symptoms and psychosocial functioning in adults with acute schizophrenia exacerbations, with a dosage of 2-4 mg/day compared to placebo.

As a maintenance treatment, brexpiprazole (1-4 mg/day) effectively delayed relapse in stabilized patients and was generally well tolerated, showing a low incidence of serious side effects and only moderate weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole: A Review in Schizophrenia. Frampton, JE.[2020]

Brexpiprazole, a serotonin-dopamine activity modulator, has shown efficacy in treating schizophrenia with a favorable safety profile, as evidenced by pooled data from multiple studies involving both short-term (6-week) and long-term (52-week) trials.

In the short-term studies, brexpiprazole had no significant treatment-emergent adverse events (TEAEs) above 5%, and in long-term studies, common side effects like weight gain and insomnia were reported but at lower rates compared to traditional antipsychotics, indicating it may be a safer alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of short- and long-term tolerability and safety of brexpiprazole in patients with schizophrenia. Kane, JM., Skuban, A., Hobart, M., et al.[2022]

Citations

1. revivapharma.com revivapharma.com/reviva-announces-positive-full-dataset-for-1-year-phase-3-recover-open-label-extension-study-evaluating-brilaroxazine-in-schizophrenia/

Reviva Announces Positive Full Dataset for 1-Year Phase ... Brilaroxazine led to robust broad-spectrum efficacy that was sustained over 1-year and was generally well tolerated with a discontinuation rate of 35% in this ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05184335

Safety and Efficacy of Brilaroxazine (RP5063) in ... This study is to evaluate the effect and safety of Brilaroxazine in patients with acute schizophrenia compared to the placebo short and long-term.

3. psychiatrictimes.com psychiatrictimes.com/view/open-label-phase-3-study-of-brilaroxazine-for-schizophrenia-shows-efficacy-tolerability

Open Label Phase 3 Study of Brilaroxazine for ... The RECOVER open label trial demonstrated positive results for brilaroxazine for schizophrenia.

4. psychiatrist.com psychiatrist.com/news/brilaroxazine-arrives-at-its-moment-of-truth/

Brilaroxazine Arrives at Its Moment of Truth The data showed that taking brilaroxazine once a day offered sustained, broad-spectrum efficacy while maintaining a favorable safety profile.

5. jneurology.com jneurology.com/articles/brilaroxazine-rp5063-clinical-experience-in-schizophrenia--a-new-option-to-address-unmet-needs.html

Brilaroxazine (RP5063) Clinical Experience in Schizophrenia The highest dose (50mg) of brilaroxazine showed only 2% side effect related dropouts, whereas aripiprazole 15 mg showed 10%. Pharmacokinetic and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01490086

NCT01490086 | RP5063 in Subjects With Schizophrenia or ... The objective of this study is to evaluate the efficacy and safety of RP5063 relative to placebo for the treatment of schizophrenia or schizoaffective disorder.