A phase 3 trial of brexpiprazole once-weekly (QW) formulation in patients with acute schizophrenia

Prior treatment

• 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 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 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 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

Other illness

• 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.

Other

• Patients presenting a first episode of schizophrenia based on the clinical judgment of the investigator
• Patients judged by the investigator to be unsuitable for participation in the trial
• 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 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