A multicenter, placebo-controlled, randomized, double-blind, parallel-group comparison trial to investigate the efficacy and safety of brexpiprazole once-weekly (QW) formulation in patients with acute schizophrenia
- Trial ID
- 2022-500583-36-00
- Protocol
- 331-102-00062
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to confirm the **efficacy** of the brexpiprazole once-weekly (QW) formulation compared to placebo in managing acute symptoms of **schizophrenia**. This is clinically relevant as it aims to establish the therapeutic potential of brexpiprazole QW in providing symptom relief for patients experiencing acute episodes of schizophrenia, potentially offering a new treatment option with a convenient dosing schedule.
Secondary objectives include evaluating the safety of the brexpiprazole QW formulation versus placebo in patients with acute schizophrenia. This assessment is crucial to ensure that the treatment is not only effective but also safe for patient use, thereby supporting its potential integration into clinical practice.
Participants
The clinical trial investigating the efficacy of brexpiprazole QW formulation for **acute schizophrenia** involves a total of 363 participants. The study population comprises both male and female subjects, aged between 18 and 64 years, who are experiencing an acute episode of schizophrenia. Participants were selected based on specific inclusion criteria, including a confirmed diagnosis of schizophrenia according to DSM-5® standards, and a requirement for hospitalization due to an acute relapse. The trial does not include a vulnerable population. Participants are expected to have experienced a recurrence or exacerbation of symptoms during an antipsychotic-free period, excluding the current episode. Additionally, they must have been treated with antipsychotics at appropriate doses and durations within the past year, demonstrating a response to these treatments, excluding clozapine. The trial does not specify any particular lifestyle considerations such as diet or physical activity. All participants provided written informed consent prior to the initiation of any trial-related procedures.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a once-weekly formulation of **brexpiprazole** in patients with acute schizophrenia. The trial aims to confirm the efficacy of brexpiprazole compared to a placebo in alleviating acute symptoms of schizophrenia. The study is expected to commence recruitment on April 1, 2023, and conclude by March 31, 2026. Participants will be involved in the trial for a maximum of six weeks, during which they will receive either the active drug or a matching placebo.
The trial will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the **screening visit**, eligibility will be assessed based on criteria such as age, diagnosis of schizophrenia, and current hospitalization status. Participants must have experienced an acute exacerbation of symptoms within two months prior to screening and meet specific criteria on the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions-Severity (CGI-S) scale. Follow-up visits will occur at regular intervals to monitor the participants' response to treatment and any adverse events. The **end-of-study visit** will involve a final assessment of the primary efficacy endpoint, which is the mean change from baseline in the PANSS total score at Week 6.
Participants are expected to remain in the study for the full duration unless specific conditions necessitate early termination. These conditions include significant adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial will utilize **oral administration** of the investigational product, with the active substance being brexpiprazole, provided in film-coated tablet form. The study is not classified as a low-intervention trial and is categorized as a therapeutic confirmatory trial for an unapproved product. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.
Treatment
The clinical trial involves the administration of **Brexpiprazole Fumarate** as the experimental medication. This compound is provided in the form of tablets and is intended for **oral use**. The maximum daily dose is 48 mg, with a total maximum dose of 168 mg over a treatment period of up to 6 weeks. The active substance, brexpiprazole fumarate, is of chemical origin and is manufactured by Otsuka Pharmaceutical Co., Ltd. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.
In addition to the experimental medication, the trial includes the use of **RXULTI 1 mg film-coated tablets** as a comparator treatment. These tablets also contain brexpiprazole as the active substance and are administered orally. The maximum daily dose for RXULTI is 1 mg, with a total maximum dose of 2 mg over a treatment period of up to 2 weeks. The tablets are produced by Otsuka Pharmaceutical Netherlands B.V. and are packaged in blisters specifically modified for clinical use, containing 2 tablets per blister.
A **Brexpiprazole Fumarate-matching Placebo** is utilized as a control in this placebo-controlled trial. The placebo is designed to match the appearance of the brexpiprazole fumarate tablets to maintain the double-blind nature of the study. The placebo is administered orally, following the same dosing schedule as the active treatment, to ensure consistency in administration across all participant groups.
Efficacy
The efficacy of the brexpiprazole once-weekly (QW) formulation in patients with acute **schizophrenia** will be assessed through a multicenter, placebo-controlled, randomized, double-blind, parallel-group comparison trial. The primary efficacy endpoint is the mean change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Week 6. This scale is a widely used tool for measuring symptom severity in schizophrenia, and changes in the PANSS total score will provide a quantitative measure of the drug's efficacy.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients at least 18 years of age and below the age of 75 at the time of informed
- Patients with a diagnosis of schizophrenia based on DSM-5® (295.90) (multiple episodes, currently in acute episode) and confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I.) at the time of informed consent
- Patients who are hospitalized, or judged to require hospitalization, for acute relapse of schizophrenia at the time of informed consent
- Patients whose current episode developed within 2 months prior to screening
- Patients with acute exacerbation of psychotic symptoms and a marked decline in daily functioning who meet all of the following criteria when the placebo administration period begins: (a) PANSS total score of ≥ 70 (b) Scores of ≥ 4 (moderate) for at least 2 of 4 PANSS items (Hallucinatory Behavior, Unusual Thought Content, Conceptual Disorganization, Suspiciousness/Persecution) (c) CGI-S score of ≥ 4 (moderately ill)
- Patients who were treated with antipsychotics at appropriate doses (recommended doses for the treatment of schizophrenia indicated in the package insert of the drug provided by the manufacturer/distributor) for appropriate durations (at least 6 weeks) and who are considered to have responded to the antipsychotics (excluding clozapine) within 12 months prior to informed consent
- Patients who experienced a recurrence or exacerbation of symptoms during an antipsychotic-free period (excluding the current episode)
- Patients who are able to provide written informed consent prior to initiation of any trial-related procedures
Exclusion Criteria
- Patients presenting a first episode of schizophrenia based on the clinical judgment of the investigator
- Patients who are considered resistant/refractory to antipsychotic treatment. Patients who are “unresponsive to medication with 2 or more antipsychotics at effective doses for a sufficiently long duration (6 weeks)” will be deemed resistant/refractory to antipsychotic treatment.
- Patients who have a history of treatment with clozapine for schizophrenia
- Patients experiencing acute depressive symptoms within 30 days prior to informed consent that, in the judgment of the investigator, require treatment with an antidepressant
- Patients who fall under any of the following criteria regarding suicidal ideation and suicidal behavior. • Patients who answered “yes” to Question 4 “Active Suicidal Ideation with Some Intent to Act, without Specific Plan” or Question 5 “Active Suicidal Ideation with Specific Plan and Intent” regarding C-SSRS suicidal ideation at screening (for the past 6 months) or at baseline (since the last assessment) • Patients who exhibited suicidal behavior on C-SSRS at screening (for the past 2 years) or at baseline (since the last assessment) • Patients who present a serious risk of suicide based on the judgment of the investigator
- Patients presenting tardive dyskinesia at the time of informed consent, as determined by a score of 3 (moderate) or 4 (severe) for Item 8 (severity of abnormal movements) of the AIMS at screening or at baseline
- Patients with a score of 5 (severe akathisia) in the BARS global clinical assessment of akathisia at screening or at baseline
- Patients who meet either of the following criteria between 30 days before screening and the start of screening (a) Received 2 or more antipsychotics, each at doses equivalent to ≥ 600 mg/day of chlorpromazine (b) Received a mean daily dose equivalent to > 800 mg/day*,** of chlorpromazine *If multiple antipsychotics are taken in the same day, this is to be the combined equivalent dose. **This does not include administration of antipsychotic medication at doses equivalent to less than 100 mg/day of chlorpromazine, which are not expected to have any antipsychotic effect. Chlorpromazine equivalent doses are based on Equivalent Conversion Table for Antipsychotics, as specified separately.
- Patients with a diagnosis of a concurrent mental disorder besides schizophrenia (schizoaffective disorder, major depressive disorder, bipolar I disorder, bipolar II disorder, general anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, dementia or mild neurocognitive disorder, personality disorder, etc) based on DSM-5®. However, this exclusion does not apply to the following: • Caffeine- or tobacco-related disorders
- Patients who have met the DSM-5® diagnostic criteria for substance-related or addictive disorder, including alcohol and benzodiazepines but excluding caffeine and tobacco, within 180 days before commencement of investigational medicinal product (IMP) administration
- Patients who have a clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorder. Medical conditions that are minor or well-controlled may be considered acceptable if the condition does not interfere with safety and efficacy assessments.
- Patients with known hypersensitivity or intolerance to brexpiprazole or patients with confirmed resistance to brexpiprazole therapy. Patients who have received brexpiprazole to treat the current episode.
- Patients judged by the investigator to be unsuitable for participation in the trial
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Romania | Recruiting | 01 Apr 2023 | 123 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Brexpiprazole Fumarate | Test | TABLETS | ORAL USE | 48 | 6 | PRD9963990 |
Brexpiprazole Fumarate-matching Placebo | Placebo | N/A | — | — | — | N/A |
RXULTI 1 mg film-coated tablets | Other | FILM-COATED TABLETS | ORAL USE | 1 | 2 | PRD6642534 |