Pharmacokinetics, tolerability and safety of aripiprazole once-monthly in adult schizophrenia: An open-label, parallel-arm, multiple-dose study

This 24-week, open-label, Phase Ib, parallel-arm, multiple-dose trial assessed the pharmacokinetics, safety and tolerability of a once-monthly injection of aripiprazole (aripiprazole once-monthly) in 41 subjects with schizophrenia. The objective was to determine if aripiprazole plasma concentrations (at doses of 200, 300 and 400 mg) were within the therapeutic range observed for the oral tablet (10-30 mg). Completion rates were 36.4% (n = 4/11), 50.0% (n = 8/16) and 71.4% (n = 10/14) for the 200 mg, 300 mg and 400 mg groups, respectively. Patients were stabilized on oral aripiprazole (10 mg/day) before the first injection and received oral aripiprazole (10 mg/day) concomitantly with the first dose of aripiprazole once-monthly for 14 days. Administration of aripiprazole once-monthly at doses of 300 and 400 mg provided sustained mean aripiprazole plasma concentrations comparable with the concentration range observed following multiple consecutive daily doses of oral aripiprazole. In contrast, plasma concentrations following administration of aripiprazole once-monthly at a dose of 200 mg were below the therapeutic range and pharmacokinetic parameters were not proportional to the administered dose compared with the 300 mg and 400 mg doses. Treatment with aripiprazole once-monthly, at any dose, did not result in any clinically meaningful changes from baseline in extrapyramidal symptom scales, clinical laboratory tests, vital signs, or electrocardiogram parameters. The most common treatment-emergent adverse events were vomiting (13.3%, 300 mg; 14.3%, 400 mg), injection site pain (28.6%, 400 mg), upper respiratory tract infection (10%, 200 mg; 6.7% 300 mg; 14.3%, 400 mg) and tremor (6.7%, 300 mg; 21.4%, 400 mg). In conclusion, aripiprazole once-monthly at doses of 300 and 400 mg is a viable formulation for treatment of adults with schizophrenia.