Pharmacokinetic Profile of Multiple-Dose Aripiprazole 2-Month Ready-to-Use 960 mg Versus Aripiprazole Once-Monthly 400 mg in Adults With Schizophrenia or Bipolar I Disorder

Abstract: Background: Aripiprazole 2-month ready-to-use 960 mg (2MRTU 960) is a new long-acting injectable (LAI) antipsychotic formulation for gluteal administration every 2 months, intended for the treatment of schizophrenia and maintenance monotherapy treatment of bipolar I disorder (BP-I). This 32-week trial evaluated the safety, tolerability, and pharmacokinetics of multiple-dose administration of 2MRTU 960 in adult patients with a diagnosis of schizophrenia or BP-I, versus that of aripiprazole once-monthly 400 mg (AOM 400; an LAI indicated for the treatment of schizophrenia and maintenance monotherapy treatment of BP-I). Methods: Patients were randomized to receive 2MRTU 960 every 56±2 days (n=132) or AOM 400 every 28±2 days (n=134). The primary objective was to establish the similarity of aripiprazole concentrations on the last day of the dosing interval, as well as exposure during the dosing interval (area under the concentration-time curve [AUC]), between 2MRTU 960 and AOM 400 following multiple doses. It was pre-specified that the lower bound of the 90% confidence interval (CI) of the geometric means ratio (GMR) for these parameters must be >0.8. Results: The GMR of C56 for 2MRTU 960 to C28 for AOM 400 was 1.011 (90% CI: 0.893, 1.145). The GMR (90% CI) of AUC0–56 for 2MRTU 960 to AUC0–28 for AOM 400 was 1.006 (90% CI: 0.851, 1.190). Mean (standard deviation) maximum aripiprazole plasma concentration was 342 (157) ng/ml after the fourth 2MRTU 960 dose and 344 (212) ng/ml after the eighth AOM 400 dose. Conclusion: Pharmacokinetic parameters were similar between 2MRTU 960 and AOM 400.Short Description: Aripiprazole 2-month ready-to-use 960 mg (2MRTU 960) is a new long-acting injectable antipsychotic formulation for gluteal administration every 2 months, intended for the treatment of schizophrenia and maintenance monotherapy treatment of bipolar I disorder. This 32-week trial evaluated the safety, tolerability, and pharmacokinetics of 2MRTU 960 versus aripiprazole once-monthly 400 mg. Aripiprazole plasma concentrations on the last day of the dosing interval, aripiprazole exposure, and maximum aripiprazole plasma concentrations were similar between the formulations.Name of Sponsoring Organization(s): Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA H. Lundbeck A/S, Valby, Denmark