Long-term Safety, Tolerability, and Effectiveness of TV-46000—a Long-Acting Subcutaneous Antipsychotic (LASCA)—in Patients With Schizophrenia: A Phase 3, Randomized, Double-Blind Study (SHINE)

Abstract: Background: TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) that combines risperidone and an innovative, copolymer-based drug delivery technology. In the RISE study (NCT03503318), TV-46000 once monthly (q1m) and once every two months (q2m) significantly extended time to impending relapse compared with placebo in patients with schizophrenia. The SHINE study (NCT03893825) evaluated the long-term safety, tolerability, and effectiveness of TV-46000. Methods: Patients who completed RISE without relapse (rollover) or who were newly recruited (de novo) were eligible. The de novo cohort and patients who received placebo in RISE were randomized 1:1 to q1m or q2m for up to 56 weeks; patients who received TV-46000 in RISE continued assigned regimen. Results: 334 patients (109 de novo, 225 rollover [172 TV-46000, 53 placebo]) were randomized and received TV-46000 q1m (n=172) or q2m (n=162), with 202.3 patient-years [PY] of TV-46000 exposure overall. The most frequent treatment-emergent adverse events (AEs) (≥5% of patients) were: overall cohort–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo cohort–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), and urinary tract infection (10.69, 7 [6%]); placebo rollover cohort–tremor (18.50, 5 [9%]); TV-46000 rollover cohort–headache (7.97, n=8 [5%]). Serious AEs (≥2 patients) were worsening schizophrenia and hyperglycemia. Kaplan–Meier estimates of patients remaining relapse free by week 56 were 0.98 (2% risk) for q1m and 0.88 (12%) for q2m. Conclusions: TV-46000 had a favorable benefit–risk profile, consistent with other formulations of risperidone and previous TV-46000 studies.Short Description: TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) that combines risperidone and an innovative copolymer based drug delivery technology. The SHINE study evaluated the long-term safety, tolerability, and effectiveness of TV-46000 once monthly (q1m) and once every two months (q2m) in patients with schizophrenia. Most frequent treatment-emergent adverse event (≥5% of patients) was injection site pain. Kaplan-Meier estimates of remaining relapse free by week 56 were 0.98 (2% risk) for q1m and 0.88 (12%) for q2m.Name of Sponsoring Organization(s): Teva Branded Pharmaceutical Products R&D, Inc.