ORIGINAL ARTICLESA phase II study to evaluate the pharmacokinetics, safety, and tolerability of Risperidone ISM multiple intramuscular injections once every 4 weeks in patients with schizophreniaCarabias, Lourdes A.a; Llaudó, Jordia; Ayani, Ignacioa; Martínez, Javiera; Litman, Robert E.b; Gutierro, IbónaAuthor Information aLaboratorios Farmacéuticos ROVI, Madrid, Spain bCBH Health, LLC, Rockville, Maryland, USA Correspondence to Lourdes A. Carabias, PhD, Laboratorios Farmacéuticos ROVI, S.A. Calle Alfonso Gómez, 45A, 28037 Madrid, Spain Tel: +34 917 617 587; fax: +34 913 047 881; e-mail: [email protected] Received July 13, 2017 Accepted October 10, 2017 International Clinical Psychopharmacology: March 2018 - Volume 33 - Issue 2 - p 79-87 doi: 10.1097/YIC.0000000000000203 Buy Metrics Abstract This study characterized the pharmacokinetics, safety, and tolerability of Risperidone ISM, a new long-acting intramuscular formulation, for monthly administration without oral supplementation. Patients with schizophrenia received multiple intramuscular injections of 75 mg in the gluteal or deltoid muscle at 28-day intervals. Of the 70 randomized patients, 67 received at least one dose of study medication. The mean Cmax of the active moiety was achieved 24–48 h (tmax) after each administration, regardless of injection site. They ranged over four consecutive doses from 39.6 to 53.2 and 54.1 to 61 ng/ml, when given in gluteal or deltoid muscle, respectively. Active moiety achieved therapeutic levels by 2 h after dose, and the levels were maintained throughout the 4-week dosing period. No significant changes across the study were observed on either Positive and Negative Syndrome Scale or Extrapyramidal Symptoms Scale. Overall, 63 (94%) patients experienced at least one treatment-emergent adverse event (TEAE). One serious TEAE (dystonia) was related to study treatment. The most frequently reported TEAEs were hyperprolactinaemia (57.7%) and injection site pain (32.8%). Risperidone ISM achieved therapeutic levels from the first hours after drug administration and provided a sustained release throughout the 4-week dosing period over multiple intramuscular injections and was found to be safe and well tolerated. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.