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
Creators: name: McIntyre, Roger S.
name: Such, Pedro
name: Yildirim, Murat
name: Madera-McDonough, Jessica
name: Zhang, Zhen
name: Larsen, Frank
name: Harlin, Matthew
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Neuroscience
subject: Physiology
subject: Pharmacology
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Mental Health
subject: Infectious Diseases
subject: FOS: Health sciences

description: 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. Patients with BP-I were randomized to receive Ari 2MRTU 960 (<i>n</i> = 40) every 56 ± 2 days (4 injections scheduled) or aripiprazole once-monthly 400 mg (AOM 400; <i>n</i> = 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 the 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. 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]; <i>p</i> = .5468). The most frequently reported TEAE was increased weight (Ari 2MRTU 960: 25.0% [10/40]; AOM 400: 26.8% [11/41]; <i>p</i> = 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]; <i>p</i> = .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 (<i>p</i> = .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 (<i>p</i> = .8995), MADRS Total (<i>p</i> = .3185), and CGI-BP scores (<i>p</i> = .8485), and in mean CGI-I score (<i>p</i> = .7960). LS mean change from baseline in SWN-S score was greater for Ari 2MRTU 960 than for AOM 400 at Week 32 (<i>p</i> = .0169). Ari 2MRTU 960 was well tolerated in patients with BP-I, with efficacy similar to AOM 400. ClinicalTrials.gov identifier: NCT04030143.