Safety and Efficacy of Brilaroxazine (RP5063) in Schizophrenia

Schizophrenia Clinical Trial

— RECOVER  

Official title:

Phase 3, Randomized, 28 Days, Double-blind, Placebo-controlled, Multicenter Study to Assess the Safety and Efficacy of Brilaroxazine (RP5063) in Subjects With Schizophrenia, Followed by a 52-Week Open-label Extension

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05184335
• Other study ID #: RVP-30-001 RECOVER
• Status: Recruiting
• Phase: Phase 3
• Start date: January 24, 2022
• Est. completion date: October 31, 2024

Study information

• Verified date: February 2024
• Source: Reviva Pharmaceuticals
• Contact: Medical Director
• Phone: +1 4085018881
• Email: medicaldirector[@]revivapharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to evaluate the effect and safety of Brilaroxazine in patients with acute schizophrenia compared to the placebo short and long-term. Brilaroxazine will be given at fixed doses of 15 mg or 50 mg once daily over 4 weeks, then in the long-term flexible doses 15-50mg daily over a period of 52 weeks.

Description:

This is a randomized, double-blind (DB), placebo-controlled, multicenter study to assess the efficacy and safety of RP5063 (brilaroxazine) at fixed doses of 15 mg or 50 mg, administered once daily (OD) for 28 days (28 days DB treatment) in subjects with an acute exacerbation of schizophrenia. The study further will assess the safety of RP5063 (brilaroxazine) at flexible doses of either 15, 30 or 50 mg administered OD in an Open Label (OL) treatment over a period of 52 weeks (52-week OL treatment part), in subjects with stable schizophrenia. The OL treatment will have 2 populations of stable schizophrenia: DB rollover and de novo subjects.

The study comprises 2 parts: a 28-day DB treatment, followed by 52 weeks OL treatment.

The total duration of the study is 56 weeks (28 days/4 weeks DB treatment and 52-weeks OL treatment).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 402
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Subject is male or female, aged 18 to 65 years

2. 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

3. Diagnosis schizophrenia

Exclusion Criteria:

1. Has a history of treatment resistance exhibited by any of the following:

1. No or minimal response to at least 2 periods of treatment lasting 28 days or longer, with antipsychotic agents at the maximally tolerated dose.

2. Lifetime history of clozapine use

3. History of electroconvulsive therapy (ECT) for treatment of schizophrenia within the past 5 years.

2. Is treatment-naïve for schizophrenia.

3. Primary current diagnosis other than schizophrenia or a comorbid diagnosis that is primarily responsible for the current symptoms and functional impairment.

4. Has a current diagnosis of a psychotic disorder other than schizophrenia or a behavioral disturbance thought to be due to substance abuse disorder.

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

6. Has a history of the following: (a) traumatic brain injury causing ongoing cognitive difficulties, Alzheimer's disease, or another form of dementia, or any chronic organic disease of the central nervous system (CNS) (b) intellectual disability of a severity that would impact ability to participate in the study.

7. Subject has a current primary DSM-5 diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, post-traumatic stress disorder, obsessive-compulsive disorder, manic episode, hypomania, panic disorder, delirium, amnestic or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.

8. On antipsychotic within the Screening Period (minimum 3 days prior to Baseline and throughout the study).

9. Within 28 days prior to Baseline: monoamine oxidase (MAO) inhibitors, CNS stimulants, potent CYP3A4/5 enzyme-inducing drugs including but not limited to rifampin and carbamazepine and strong CYP3A4/5 inhibitors like ketoconazole, itraconazole, clarithromycin, etc. (see Appendix 20.1 for prohibited medications).

10. Antipsychotic depot medication within 5 half-lives prior to Baseline.

11. 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.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Brilaroxazine
RP5063, a new chemical entity (NCE), is a novel multimodal neuromodulator intended for treating schizophrenia and comorbid conditions. This drug is an investigational drug and has not been approved for treatment or marketing. RP5063 belongs to a class of third generation antipsychotics called Dopamine-Serotonin System Stabilizers. The chemical name of the RP5063 active pharmaceutical ingredient (API) is 6-(4-(4-(2,3-dichlorophenyl)-piperazin-1-yl)-butoxy)-2H-benzo[b][1,4]oxazin-3(4H)-one hydrochloride.

Other:
• Placebo
RP5063 matching Placebo

Locations

Country	Name	City	State
United States	Reviva site	Atlanta	Georgia
United States	Reviva site	Austin	Texas
United States	Reviva site	Bentonville	Arkansas
United States	Reviva site	Boston	Massachusetts
United States	Reviva site	Chicago	Illinois
United States	Reviva site	Decatur	Georgia
United States	Reviva site	Gaithersburg	Maryland
United States	Reviva site	Garden Grove	California
United States	Reviva site	Hollywood	Florida
United States	Reviva site	Hollywood	Florida
United States	Reviva site	Lemon Grove	California
United States	Reviva site	Little Rock	Arkansas
United States	Reviva site	Miami Lakes	Florida
United States	Reviva site	Oklahoma City	Oklahoma
United States	Reviva site	Phoenix	Arizona
United States	Reviva site	Richardson	Texas
United States	Reviva site	Riverside	California
United States	Reviva site	Rogers	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
Reviva Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Double Blind Safety and Efficacy of Brilaroxazine (RP5063)	decrease in Positive and Negative Symptoms Assessment total score compared to placebo from Baseline to Day 28.	28 days
Primary	Open label Safety and Efficacy of Brilaroxazine (RP5063)	(brilaroxazine) tablets (at flexible doses of 15 mg or 30 mg 0r 50mg OD) in an treatment part over a period of 52 weeks in stable schizophrenia subjects. The endpoints would be incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])	52 weeks