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.

Efficacy and safety of once-monthly Risperidone ISM® in schizophrenic patients with an acute exacerbation

“…Both doses of Risperidone ISM ® were well tolerated. The adverse events (AEs) observed were those expected for oral and LAI risperidone at therapeutic doses 17 and were consistent with that observed in previous studies with Risperidone ISM ®11, 12 .…”

“…A unique randomization number was assigned via Interactive Web Response System (IWRS) accessed immediately after eligibility confirmation of a patient. The doses selected for this study were supported by the results obtained from previously conducted studies, 11,12 as well as pharmacokinetic modeling 26 .…”

“…Risperidone ISM ® is a new long-acting injectable (LAI) intramuscular (IM) formulation of risperidone, for monthly administration without the need of using oral supplementation or loading doses, as it has been shown previously 11,12 .…”

The Steady-State Comparative Bioavailability of Intramuscular Risperidone ISM and Oral Risperidone: An Open-Label, One-Sequence Study

“…Nevertheless, overall, no new safety signals were detected, and the adverse events observed were those expected for risperidone at therapeutic doses. 21,22 Furthermore, the TEAEs reported were in line with those observed in previous studies with Risperidone ISM 4,5 and the overall dropout rate was also in agreement with those reported in other studies with antipsychotics. [23][24][25] Most treatment-related TEAEs reported were mild or moderate in severity, leading to study drug discontinuation in only two subjects (2.5%), one due to sedation whilst receiving oral treatment and one due to akathisia following a Risperidone ISM dose.…”

“…6 The ISM technology enables the extended delivery of compounds with the following advantages: less variability, enhanced stability, rapid reconstitution, and straightforward injection, making it uncomplicated for the patient and provider to follow the prescribed treatment. 4 The aim of this study was to evaluate the steady-state comparative bioavailability, safety, and tolerability of risperidone ISM and oral risperidone, as well as provide evidence that the direct switch from oral risperidone to Risperidone ISM is appropriate.…”