Safety and efficacy of aripiprazole 2-month ready-to-use 960 mg: secondary analysis of outcomes in adult patients with bipolar I disorder in a randomized, open-label, parallel-arm, pivotal study.

Objective : Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable antipsychotic formulation for administration every 2 months. A 32-week trial evaluated the safety, tolerability, and pharmacokinetics of Ari 2MRTU 960 in clinically stable adults with schizophrenia or bipolar I disorder (BP-I) (per DSM-5 criteria). This secondary analysis evaluated the safety and efficacy of Ari 2MRTU 960 in the subpopulation of patients with BP-I. Methods: Patients with BP-I were randomized to receive Ari 2MRTU 960 (n = 40) every 56 ± 2 days (4 injections scheduled) or aripiprazole once-monthly 400 mg (AOM 400; n = 41) every 28 ± 2 days (8 injections scheduled). Data were collected during August 2019-July 2020 across 16 US sites. Primary safety endpoints included reported adverse events (coded by the Medical Dictionary for Regulatory Activities preferred term), injection site reactions (assessments included a Visual Analog Scale [VAS] to evaluate patient-reported injection-site pain), and motoric symptoms. Secondary endpoints for efficacy included change from baseline at Week 32 in Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression - Bipolar Version (CGI-BP), and Subjective Well-being under Neuroleptic Treatment - Short Form (SWN-S) scores, and Clinical Global Impression - Improvement (CGI-I) at Week 32. Results: The incidence of treatment-emergent adverse events (TEAEs) was similar between Ari 2MRTU 960 (82.5% [33/40]) and AOM 400 (87.8% [36/41]; p = 0.5468). The most frequently reported TEAE was increased weight (Ari 2MRTU 960: 25.0% [10/40]; AOM 400: 26.8% [11/41]; p = 1). Injection-site pain was experienced by more patients in the Ari 2MRTU 960 group (25% [10/40]) versus the AOM 400 group (7.3% [3/41]; p = 0.0622). Mean (standard deviation [SD]) VAS scores for patient-reported injection-site pain following the last injection were 1.2 (2.07) for Ari 2MRTU 960 group and 1.3 (2.19) for AOM 400 (p = 0.9479) (VAS scale range 0-100 [no pain-extreme pain]). No notable improvement or decline from baseline was observed in motoric symptoms in either treatment group. Patients in both treatment groups remained clinically stable for the entire 32-week trial duration, with minimal difference between treatment groups in the least squares (LS) mean change from baseline at Week 32 in the YMRS Total (p = 0.8995), MADRS Total (p = 0.3185), and CGI-BP scores (p = 0.8485), and in mean CGI-I score (p = 0.7960). LS mean change from baseline in SWN-S score was greater for Ari 2MRTU 960 than for AOM 400 at Week 32 (p = 0.0169). Conclusions: Ari 2MRTU 960 was well tolerated in patients with BP-I, with efficacy similar to AOM 400.Trial registration: ClinicalTrials.gov identifier: NCT04030143.