Aripiprazole plasma concentrations delivered from two 2-month long-acting injectable formulations: an indirect comparison

Abstract: Background: Aripiprazole 2-month ready-to-use 960 mg (2MRTU 960) is a new formulation of aripiprazole monohydrate intended for the treatment of schizophrenia or maintenance monotherapy treatment of bipolar I disorder (BP-I). Aripiprazole lauroxil 2-month 1064 mg (AL 1064) is indicated for treatment of schizophrenia. This indirect comparison examined aripiprazole plasma concentrations delivered from each formulation following multiple-dose administration. An individual with a diagnosis of schizophrenia and a predicted minimum aripiprazole plasma concentration (Cmin) ≥95 ng/mL is 4.41 times less likely to relapse, compared with an individual with a predicted Cmin < 95 ng/mL. Methods: For each formulation, data from patients who received four administrations (96 patients with schizophrenia or BP-I received 2MRTU 960; 28 patients with schizophrenia received AL 1064) were used to determine average steady-state aripiprazole plasma concentration (Cavg,ss) and maximum aripiprazole plasma concentration (Cmax). Data were considered in the context of the minimum therapeutic threshold of 95 ng/mL. Results: Following four administrations, mean Cavg,ss over the 2-month dosing interval remained above the minimum therapeutic threshold with both formulations – 2MRTU 960: 263 (standard deviation [SD]: 133) ng/mL; AL 1064: 140.7 (SD: 57.3) ng/mL. Mean Cmax during the fourth dosing interval was 342 (SD: 157) ng/mL for 2MRTU 960 and 188.8 (SD: 79.8) ng/mL for AL 1064. Conclusion: This indirect comparison showed that 2MRTU 960 and AL 1064 both delivered aripiprazole plasma concentrations that remained above the minimum therapeutic threshold over the 2-month dosing interval.Short Description: Aripiprazole 2-month ready-to-use 960 mg (2MRTU 960) is a new formulation of aripiprazole monohydrate, intended for the treatment of schizophrenia or bipolar I disorder. Aripiprazole lauroxil 2-month 1064 mg (AL 1064) is indicated for treatment of schizophrenia. This indirect comparison examined available observed data for aripiprazole plasma concentrations delivered from each formulation following multiple-dose administration. Over the 2-month dosing interval, both formulations delivered aripiprazole plasma concentrations above the minimum therapeutic threshold of 95 ng/mL.Name of Sponsoring Organization(s): Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA Lundbeck LLC, Deerfield, IL, USA