Pharmacokinetics and Safety of RYKINDO® (Risperidone) for Extended-Release Injectable Suspension, a Novel Long-Acting Injectable Risperidone, in Patients With Schizophrenia and/or Schizoaffective Disorder

This work was sponsored by Shandong Luye Pharmaceutical Co., Ltd. RYKINDO® (LY03004) is a novel long-acting injectable (LAI) risperidone for the treatment of schizophrenia in adults, formulated as extended-release microspheres for intramuscular (IM) injection in the gluteal muscle every 2 weeks (Q2W). This phase 1, multicenter, randomized, open-label study comparatively evaluated the pharmacokinetics and safety of RYKINDO and RISPERDAL CONSTA® (RC), a risperidone LAI Q2W comparator, in patients with stable schizophrenia/schizoaffective disorder (NCT02091388). A total of 108 patients aged 18-65 years were randomized (1:1) to receive 5 IM injections Q2W of RYKINDO 25 mg or RC 25 mg (n=54/arm). The primary endpoint was the evaluation of the relative bioavailability of these drugs at steady state. Plasma samples were analyzed using liquid chromatographic-mass spectrometry. Pharmacokinetic data were generated using noncompartmental methods. Following injection, plasma active moiety (risperidone and 9-hydroxyrisperidone combined) levels increased without an apparent lag time for RYKINDO vs a 3-week lag for RC. Plasma active moiety levels for RYKINDO and RC reached steady state after the second and third injections, respectively. At steady state, after all 5 injections, mean plasma concentrations of the active moiety were similar for RYKINDO and RC. Statistical analysis showed that 90% CIs of the geometric least squares mean ratios (RYKINDO:RC) for Cmax-ss and AUCtau-ss were within the bioequivalence limits (80%–125%), demonstrating bioequivalence at steady state. The elimination phase for RYKINDO was completed approximately 2 weeks earlier than for RC. The safety/tolerability profiles were generally similar for RYKINDO and RC. Overall, RYKINDO exhibited a faster onset and offset than RC and was well tolerated.