Evaluate Pharmacokinetics, Safety, and Tolerability of AX251 LAI in Patients With Schizophrenia

Inclusion criteria

• Male or female subjects aged 18 to 65 years (inclusive).
• clinical diagnosis of schizophrenia per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) (or later) criteria, at screening.
• Body Mass Index (BMI) 18.5-35.0 kg/m² at screening.
• Clinical Global Impression-Severity (CGI-S) score ≤4 at screening.
• Positive and Negative Syndrome Scale (PANSS) total score ≤75 at screening.
• Clinically stable schizophrenia on current antipsychotic medication other than cariprazine for at least 3 months prior to screening.
• Subjects must not be taking more than two antipsychotic medications.
• Able to remain at the study site for 7 days following AX251 LAI injection.
• Judged by the investigator to be physically and mentally able to participate in the study based on clinical evaluation, physical examination, electrocardiogram (ECG), and laboratory assessments.
• Willing and able to comply with study procedures.
• Agrees to use protocol-defined contraception during the study.
• Previous tolerability to oral cariprazine (1.5-6 mg) or willingness to undergo a short oral tolerability test (2-7 days) followed by washout before study drug administration.

Exclusion criteria

• Diagnosis of psychiatric disorders other than schizophrenia according to DSM-5-TR (e.g., schizoaffective disorder, major depressive disorder, bipolar disorder, generalized anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, dementia, mild neurocognitive disorder, or personality disorders), except caffeine- or tobacco-related disorders.
• Substance use disorder (including alcohol or benzodiazepines) within 180 days prior to screening, excluding caffeine and tobacco.
• History of neuroleptic malignant syndrome, seizure disorder, or clinically significant tardive dyskinesia, akathisia, or extrapyramidal symptoms.
• Clinically significant cardiovascular, hematologic, metabolic, hepatic, renal, immunologic, or neurological disease that may interfere with study participation.
• Severe hepatic impairment (Child-Pugh Class C) at screening.
• Uncontrolled hypertension.
• Clinically significant electrocardiogram abnormalities at screening.
• Severe renal impairment (estimated glomerular filtration rate <30 mL/min).
• History of syncope or significant orthostatic hypotension at screening.
• Failure to complete required washout period (≥5 half-lives) for prohibited medications before administration of AX251 LAI.
• Current treatment with other antipsychotic long-acting injectable (LAI) therapies.
• Electroconvulsive therapy within 60 days prior to screening.
• Acute psychosis posing imminent risk to self or others.
• Acute relapse of schizophrenia at screening.