title: Phase I, open-label, randomized, parallel study to evaluate the pharmacokinetics, safety, and tolerability of one intramuscular injection of risperidone ISM at different dose strengths in patients with schizophrenia or schizoaffective disorder (PRISMA-1).
abstract: The aim of this study was to characterize the pharmacokinetics and to evaluate the safety of risperidone ISM in patients with schizophrenia or schizoaffective disorder after a single gluteal intramuscular injection at three different dose strengths (50, 75, and 100 mg). A total of 36 patients were randomized and blood samples were collected to measure the plasma concentrations. The pharmacokinetic of the active moiety was biphasic for all three dose groups, and the mean plasma concentration was 21.45, 24.60, and 29.68 ng/ml in the 50, 75, and 100 mg group, respectively, 24 h after dose administration; 22.81, 24.57, and 31.41 ng/ml in the 50, 75, and 100 mg group, respectively, 48 h after dose administration, and 12.26, 17.31, and 20.01 ng/ml in the 50, 75, and 100 mg group, respectively, 30 days after dose administration. Overall, 34 patients experienced at least one treatment-emergent adverse event (TEAE). Two patients experienced a serious TEAE and no deaths occurred. There were no extrapyramidal symptoms-related serious TEAEs and no significant changes in any Columbia Suicide Severity Rating Scale parameter were observed during the study. Risperidone ISM provided a sustained release of risperidone that achieved therapeutic plasma levels within the first day. Risperidone ISM was safe, well tolerated, and should be suitable for a 4-weekly administration without oral supplementation.
authors.affiliation: aLaboratorios Farmacéuticos ROVI, Madrid, Spain bSouth Africa Clinical Trials Centre, Cape Town, South Africa cMental Health Research Center of RAMS, Moscow dSaint Petersburg Psycho-Neurological Research Institute, Saint Petesburg, Russia.
authors.forename: Jordi
authors.initials: J
authors.lastname: Llaudó
authors.forename: Lourdes
authors.initials: L
authors.lastname: Anta
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ayani
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez
authors.forename: Juan
authors.initials: J
authors.lastname: Schronen
authors.forename: Margarita
authors.initials: M
authors.lastname: Morozova
authors.forename: Mikhail
authors.initials: M
authors.lastname: Ivanov
authors.forename: Ibón
authors.initials: I
authors.lastname: Gutierro
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D012559:Schizophrenia / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone