Phase I clinical trial to evaluate the pharmacokinetics, safety, and tolerability of one intramuscular injection of risperidone ISM® at different dose strengths in subjects with Schizophrenia or Schizoaffective disorder (PRISMA-1)

Introduction: Risperidone ISM is a new long acting intramuscular injection of risperidone, intended for a 4‐weekly administration, without oral supplementation. A clinical trial was conducted to characterize the pharmacokinetics and to evaluate the safety of Risperidone ISM in subjects with schizophrenia or schizoaffective disorder (ClinicalTrials.gov identifier: NCT01788774). Material and Method: A total of 36 subjects were randomized (1:1:1) to receive a single IM injection of Risperidone ISM : 13 (50 mg), 12 (75 mg) and 11 (100 mg). Blood samples were collected through 75 days post‐dose to measure the plasma concentrations of risperidone and 9‐OH‐risperidone. Results: A total of 36 subjects received a single IM injection of Risperidone ISM. The mean plasma concentration of the active moiety (risperidone + 9‐OH‐risperidone) in the 50 mg, 75 mg, and 100 mg group, respectively, was 21.4 ng/mL, 24.6 ng/mL, and 29.6 ng/mL (24 hours after injection); 22.8 ng/mL, 24.5 ng/mL, and 31.4 ng/mL (48 hours after injection); and 12.2ng/mL, 17.3 ng/mL, and 20.0 ng/(Day 30 after injection). Overall, 34 subjects (94.4%) experienced at least 1 Treatment Emergent Adverse Event (TEAE) during the study. The percentage of subjects reporting at least 1 TEAE was similar across the 3 dose groups (92.3%, 100%, and 90.9% in the 50, 75 and 100 mg group, respectively). Two subjects experienced an SAE and no deaths occurred during the study. There were no EPS‐related SAEs and no subjects experienced significant change of any C‐SSRS parameter. Conclusions: Risperidone ISM provided a sustained release of risperidone that achieved monthly therapeutic plasma levels within the first day without oral supplementation. Risperidone ISM was found to be safe and well tolerated.