Deltoid Injection of Aripiprazole Once-Monthly in the Treatment of Schizophrenia

Objective: The deltoid muscle is evaluated as an alternative to gluteal injection of aripiprazole once-monthly 400mg (AOM 400), an extended release injectable suspension of aripiprazole for treatment of schizophrenia. Methods: Two open-label studies generated pharmacokinetic (PK) data following deltoid and gluteal injections of AOM 400 in stable adult patients with schizophrenia. Study 1 (NCT01646827): single-dose, parallel-groups; either deltoid or gluteal injection. Study 2 (NCT01909466): multiple-dose, parallel-group safety/tolerability study that randomized patients to a first AOM 400 injection in either the deltoid or gluteal muscle, followed by 4 monthly deltoid injections for all subjects. Results: Both studies showed comparable safety and tolerability after deltoid and gluteal AOM 400 injection. Study 1 treatment-emergent adverse events (TEAEs): 82.4% (deltoid, 14/17) and 100% (gluteal, 18/18) of patients. Study 2 TEAEs: 81.2% (112/138) of patients. Most frequent TEAEs: injection site pain (27.5%, 38/138), weight increased (12.3%, 17/138), headache (11.6%, 16/138), and toothache, upper respiratory tract infection, and akathisia (all three, 8.0%, 11/138), with 5.1% (7/138) of patients discontinued for TEAEs. Injection site pain after the first deltoid injection was 25.4% (18/71), decreasing to 4/122 (3.3%), 1/109 (0.9%), 0/106 (0%), and 3/100 (3.0%) with subsequent deltoid injections. Multiple AOM 400 deltoid injections provided comparable maximum and minimum aripiprazole plasma concentrations and exposures (area-under-the-curve) compared with gluteal injections measured in earlier studies. Conclusions: Deltoid muscle injection of AOM 400 is a well-tolerated alternative to gluteal injection. PK parameters after deltoid injection suggest AOM 400 efficacy should be comparable to gluteal injections.