Behavioral-, Neurologic-, Metabolic-, Endocrine-, and Cardiovascular-Related Adverse Events and Assessments in Patients With Schizophrenia Treated With TV-46000

This work was sponsored by Teva Branded Pharmaceutical Products R&D, Inc. Introduction: TV-46000 is an FDA-approved long-acting subcutaneous antipsychotic (LASCA) risperidone formulation for the treatment of schizophrenia in adults. This analysis evaluated adverse events (AEs) of special interest. Methods: RISE (NCT03503318) compared TV-46000 once monthly (q1m) and once every 2 months (q2m) with placebo. SHINE (NCT03893825) included patients who completed RISE without relapse or who were newly recruited (randomized to q1m or q2m). AEs were pooled and incidence calculated as exposure-adjusted event rate (EAER; events per 100 patient-years [PYs]). Patients in RISE and those newly recruited in SHINE were stabilized on oral risperidone for 12 weeks prior to randomization. Results: 649 patients were randomized and received treatment in RISE/SHINE (TV-46000 q1m, n=264, includes 28 patients rerandomized from placebo [PY=237.6]; TV-46000 q2m, n=261, includes 27 patients rerandomized from placebo [PY=237.0]; placebo, n=179 [PY=106.1]). Incidence (EAER) of the most frequent AEs of interest (≥3% for TV-46000 overall) were neurologic (nervous system disorders system organ class [SOC]): headache (TV-46000 q1m, 5.89; TV-46000 q2m, 8.02; placebo, 10.37), akathisia (6.31, 4.22, 5.66), extrapyramidal disorder (4.21, 3.38, 0), dizziness (4.63, 2.95, 0.94), and somnolence (3.79, 3.38, 0.94); metabolic/endocrine (endocrine disorders, investigations [metabolic/endocrine AEs], metabolism and nutrition disorders SOC): weight increased (6.31, 6.75, 5.66) and blood creatine phosphokinase increased (2.53, 6.33, 4.71); and behavioral (psychiatric disorders SOC): insomnia (6.31, 3.80, 10.37). No cardiovascular AEs (cardiac and vascular disorders SOCs) were reported for ≥3% of patients. Conclusions: No clinically meaningful trends in AEs of interest were identified in pooled data from the RISE and SHINE studies.