Long-term Safety, Tolerability, and Effectiveness of TV-46000, a Long-Acting Subcutaneous Antipsychotic (LASCA), in Patients With Schizophrenia (SHINE)

This work was sponsored by Teva Branded Pharmaceutical Products R&D, Inc. Introduction: In RISE, TV-46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV-46000. Methods: Patients completing RISE without relapse (rollover) or newly recruited (de novo) were eligible. The de novo and placebo rollover cohorts were randomized 1:1 to q1m or q2m for ≤56 weeks; the TV-46000 rollover cohort continued assigned regimen. Exploratory efficacy endpoints included time to impending relapse and patient centered outcomes (PCOs) including Schizophrenia Quality of Life Scale (SQLS). Results: 334 patients were randomized and received TV-46000 q1m (n=172) or q2m (n=162), for 202.3 patient-years [PY] of TV-46000 treatment. Treatment-emergent adverse events (AEs) reported for ≥5% of patients were: overall–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo (n=109)–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), urinary tract infection (10.69, 7 [6%]); placebo rollover (n=53)–tremor (18.50, 5 [9%]); TV 46000 rollover (n=172)–headache (7.97, n=8 [5%]). Serious AEs reported for ≥2 patients were worsening schizophrenia and hyperglycemia. Kaplan–Meier estimates for remaining relapse-free at week 56 were 0.98 (2% risk; q1m) and 0.88 (12%; q2m). SQLS improved for q1m (least-squares mean change [SE], −2.16 [0.98]) and q2m (−0.43 [0.98]); other PCOs (5-Level EuroQoL 5-Dimensions Questionnaire, Personal and Social Performance Scale, Drug Attitudes Inventory 10-item version) remained stable. Conclusions: TV-46000 had a favorable long-term benefit–risk profile in patients with schizophrenia.