PMID- 38416865 OWN - NLM STAT- MEDLINE DCOM- 20240301 LR - 20240403 IS - 1555-2101 (Electronic) IS - 0160-6689 (Linking) VI - 85 IP - 1 DP - 2024 Feb 28 TI - Safety and Tolerability of Starting Aripiprazole Lauroxil With Aripiprazole Lauroxil NanoCrystal Dispersion in 1 Day Followed by Aripiprazole Lauroxil Every 2 Months Using Paliperidone Palmitate Monthly as an Active Control in Patients With Schizophrenia: A Post Hoc Analysis of a Randomized Controlled Trial. LID - 23m15095 [pii] LID - 10.4088/JCP.23m15095 [doi] AB - Background: Aripiprazole lauroxil (AL) 1064 mg every 2 months following initiation using the AL NanoCrystal Dispersion formulation (AL(NCD)) plus 30-mg oral aripiprazole was efficacious and well tolerated in a 25-week, randomized, double-blind phase 3 trial in adults with acute schizophrenia. This post hoc analysis further characterized the safety of AL 1064 mg administered every 2 months and that of active control paliperidone palmitate (PP) 156 mg monthly based on occurrence, timing, and severity of adverse events (AEs) associated with antipsychotic medications. Methods: This study was conducted between November 2017 and March 2019. AL or PP was initiated during an inpatient stay of >/= 2 weeks with transition to outpatient treatment thereafter. Rates of AEs of clinical interest, including injection site reactions (ISRs), motor AEs, sedation, hypotension, prolactin level increase, weight gain, and suicidal ideation/behavior, were summarized through weeks 4, 9, and 25 for each treatment. Results: Of 200 patients who received >/= 1 dose of study treatment, 99 (49.5%) completed the study (AL, 57%; PP, 43%). Mean (SD) baseline Positive and Negative Syndrome Scale total scores were 94.1 (9.04) and 94.6 (8.41) in the AL and PP treatment groups, respectively. AEs were reported by 69/99 (70%) patients administered AL and 72/101 (71%) administered PP; most AEs were mild or moderate in severity. ISRs (AL, 18.2%; PP, 26.7%) occurred primarily on days 1 and 8. All akathisia/restlessness AEs (AL, 10.1%; PP, 11.9%) occurred during the first 4 weeks; <10% of patients (either treatment) experienced hypotension, sedation, or suicidal ideation/behavior events. Weight gain of >/= 7% from baseline occurred in 9.3% of AL- and 23.8% of PP-treated patients. Median prolactin concentrations changed by -4.60 and -3.55 ng/mL among AL-treated males and females, respectively, and did not exceed 2 times normal levels in any AL-treated patients. In PP-treated patients, changes were 21.20 and 80.40 ng/mL and concentrations exceeded 2 times normal in 38% and 88% of males and females, respectively. Conclusions: No new early- or late-emerging safety concerns were observed through 25 weeks of treatment with AL 1064 mg every 2 months following initiation using AL(NCD) plus 30-mg oral aripiprazole. Results were consistent with known safety profiles of AL and PP and support the safety of AL 1064 mg every 2 months initiated using AL(NCD) plus 30-mg oral aripiprazole. Trial Registration: ClinicalTrials.gov identifier: NCT03345979. CI - (c) Copyright 2024 Physicians Postgraduate Press, Inc. FAU - Citrome, Leslie AU - Citrome L AD - New York Medical College, Valhalla, New York. AD - Corresponding Author: Leslie Citrome, MD, MPH, New York Medical College, 40 Sunshine Cottage Rd, Valhalla, NY 10595 (nntman@gmail.com). FAU - Yagoda, Sergey AU - Yagoda S AD - Alkermes, Inc., Waltham, Massachusetts. FAU - Bidollari, Ilda AU - Bidollari I AD - Alkermes, Inc., Waltham, Massachusetts. FAU - Wang, Meihua AU - Wang M AD - Alkermes, Inc., Waltham, Massachusetts. LA - eng SI - ClinicalTrials.gov/NCT03345979 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240228 PL - United States TA - J Clin Psychiatry JT - The Journal of clinical psychiatry JID - 7801243 RN - 0 (Antipsychotic Agents) RN - 82VFR53I78 (Aripiprazole) RN - B786J7A343 (aripiprazole lauroxil) RN - 0 (Delayed-Action Preparations) RN - R8P8USM8FR (Paliperidone Palmitate) RN - 9002-62-4 (Prolactin) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - *Antipsychotic Agents/therapeutic use MH - Aripiprazole/therapeutic use MH - Delayed-Action Preparations/therapeutic use MH - *Hypotension/chemically induced/drug therapy MH - *Nanoparticles MH - *Noncommunicable Diseases/drug therapy MH - Paliperidone Palmitate MH - Prolactin MH - *Schizophrenia/drug therapy/chemically induced MH - Treatment Outcome MH - Weight Gain MH - Double-Blind Method EDAT- 2024/02/28 18:42 MHDA- 2024/03/01 06:44 CRDT- 2024/02/28 14:33 PHST- 2024/03/01 06:44 [medline] PHST- 2024/02/28 18:42 [pubmed] PHST- 2024/02/28 14:33 [entrez] AID - 23m15095 [pii] AID - 10.4088/JCP.23m15095 [doi] PST - epublish SO - J Clin Psychiatry. 2024 Feb 28;85(1):23m15095. doi: 10.4088/JCP.23m15095.