TV-46000—a Long-Acting Subcutaneous Antipsychotic (LASCA) for the Treatment of Schizophrenia: Local Tolerability and Injection Site Reactions

Abstract: Background: The phase 3 schizophrenia program for TV-46000, a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone, included the RISE efficacy study (NCT03503318) and the SHINE long-term safety study (NCT03893825). Methods: Patients received once-monthly subcutaneous upper-arm or abdominal injections of TV-46000, placebo, or both (alternating TV-46000/placebo for once-every-2-months regimen). If an injection site adverse event/reaction (ISR) was reported, local tolerability was assessed. Results: 649 patients were randomized and received treatment in RISE/SHINE (TV-46000, n=525; placebo, n=179 [55 rerandomized to TV-46000, counted once]). ISRs were comparable between TV-46000 (n=102, 19%) and placebo (n=22, 12%), and led to 9 (1.7%) treatment discontinuations (all TV-46000). There were no serious ISRs, and all but 1 ISR (severe injection site pruritus, TV-46000) were mild/moderate. Frequent ISRs (≥5% of patients in either group) were pain (exposure-adjusted event rate/n [%]; 15.6/36 [7%], 33.9/11 [6%]) and nodule (12.4/35 [7%], 15.1/6 [3%]). ISR frequency decreased after the first injection (48 [9%] and 11 [6%] patients) to 14 (3%) and 3 (2%) after the fifth injection and remained generally steady. Fewer ISRs were reported following upper-arm injections (18/1457 [1%] and 17/923 [2%]) than abdominal injections (168/3097 [5%] and 80/1798 [4%]). Most induration/nodule assessments were mild/moderate (