Pharmacokinetics, Safety, Tolerability and Efficacy of a Subcutaneous Long-Acting Injection of Cariprazine (Cariprazine Depot) in Subjects Eligible for Treatment With Oral Cariprazine

A Prospective, Dose Escalating, Open Label, Multi-center, Phase I/IIa Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of a Subcutaneous Long-Acting Injection of Cariprazine (Cariprazine Depot) in Subjects Eligible for Treatment With Oral Cariprazine.

The purpose of this study is to assess the PK, Safety, Tolerability (all cohorts) and Efficacy (cohort 3), of once-a-month long-acting SC injection of dose escalating Cariprazine Depot in subjects eligible for treatment with oral Cariprazine.

Key Inclusion Criteria:

• Subjects who meet DSM-5-TR diagnostic criteria for schizophrenia, bipolar I disorder or major depressive disorder (this inclusion criterion relates to cohorts 1 and 2 only).
• Clinically stable subjects (with no evidence of deterioration and on a stable dose of oral antipsychotic or antidepressant medication(s) other than Cariprazine for at least 4 weeks, prior to screening), receiving antipsychotic/s or antidepressant/s other than oral Cariprazine and eligible for treatment with Cariprazine 3 mg/day, with CGI-S score of 1-4.
• Men and women aged 18-64 years (inclusive).
• Body mass index (BMI) 18.5-35.
• Able to sign an informed consent form.
• Adult subjects with a current diagnosis of schizophrenia, who meet DSM-5-TR diagnostic criteria for schizophrenia, naïve to or treated with antipsychotics (this inclusion criterion relates to cohort 3 only).

Key Exclusion Criteria:

• Subjects with schizophrenia with PANSS item scores of > 4 on any of the following: P4 Excitement/Hyperactivity; P6 Suspiciousness/persecution; P7 Hostility; G8 Uncooperativeness; G14 Poor impulse control.
• Subjects with schizoaffective disorder, delirium, dementia, amnestic, or other cognitive disorders or severe personality disorders.
• Use of an investigational drug, and/or participation in clinical studies with an investigational product within 3 months prior to screening.
• History or current cardiovascular or cerebrovascular disease.
• History of seizures or conditions that lower the seizure threshold.
• Use of concomitant administration of strong or moderate CYP3A4 inhibitors.
• Use of concomitant medication of strong or moderate CYP3A4 inducers is contraindicated.
• Subjects with Suicidal Thoughts and Behaviors or has a history of suicidal ideation in the past year, or made a suicide attempt in the past 5 years.
• Subjects with a history of orthostatic hypotension and/or syncope.
• Subjects clinically stable on any dose of oral Cariprazine or add-on treatment (cohorts 1-2 only).
• Subjects with CGI-S score of 5-7.
• Subjects previously treated with partial D2 agonists, aripiprazole and brexipiprazole, and suffered from clinically relevant akathisia.
• For cohort 3 only: Subjects treated with oral Clozapine.