From Global Research & Development, Indivior Inc., North Chesterfield, VA.
Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL.
J Clin Psychopharmacol. 2019 Sep-Oct;39(5):428-433. doi: 10.1097/JCP.0000000000001076.
PURPOSE/BACKGROUND: The Phase 3 program for RBP-7000, a once-monthly subcutaneous (SC) extended-release risperidone formulation approved for treatment of schizophrenia, consisted of a double-blind placebo-controlled trial (previously reported) and a 52-week open-label study of monthly RBP-7000 120 mg. The primary objective of the open-label study was to evaluate the long-term safety and tolerability of RBP-7000 in adults with schizophrenia. A secondary objective was to assess long-term maintenance of effectiveness.
METHODS/PROCEDURES: The 52-week Phase 3 open-label study (NCT02203838) enrolled 92 rollover participants from the double-blind trial (NCT02109562) and 408 stable (Positive and Negative Syndrome Scale [PANSS] total score, ≤70) de novo participants. Participants received up to 13 monthly SC injections of RBP-7000 120 mg. Safety assessments included treatment-emergent adverse events, injection-site assessments, vital signs, laboratory and ECG parameters, extrapyramidal symptoms, and suicidality. Clinical outcomes included the PANSS and Clinical Global Impression-Severity.
FINDINGS/RESULTS: Overall, 367 participants (73.4%) reported 1 or more treatment-emergent adverse event; the most common were injection-site pain (13.0%) and weight increase (12.8%). Most participants (>80%) experienced no injection-site reactions. No clinically meaningful changes were observed in laboratory or electrocardiogram values, vital signs, extrapyramidal symptoms, or suicidality. Over 12 months of exposure, mean PANSS scores continued to improve in rollover participants and remained stable among de novo participants. Mean Clinical Global Impression-Severity scores remained stable among all participants.
IMPLICATIONS/CONCLUSIONS: Except for anticipated injection-site reactions, RBP-7000 demonstrated a favorable safety and tolerability profile similar to oral risperidone. Notably, PANSS scores continued to improve for participants from the pivotal study and remained stable for de novo participants.
目的/背景：RBP-7000 是一种每月一次的皮下（SC）长效利培酮制剂，用于治疗精神分裂症，已获得批准，其三期临床试验由一项双盲安慰剂对照试验（先前报道）和一项每月 RBP-7000 120mg 的 52 周开放性研究组成。开放性研究的主要目的是评估利培酮在精神分裂症成人中的长期安全性和耐受性。次要目的是评估长期疗效维持情况。
方法/程序：52 周三期开放性研究（NCT02203838）纳入了双盲试验（NCT02109562）中 92 名滚动入组参与者和 408 名稳定（阳性和阴性症状量表[PANSS]总分，≤70）初治参与者。参与者接受了多达 13 次每月 SC 注射 RBP-7000 120mg。安全性评估包括治疗后出现的不良事件、注射部位评估、生命体征、实验室和心电图参数、锥体外系症状和自杀意念。临床结局包括 PANSS 和临床总体印象严重度。
总体而言，367 名参与者（73.4%）报告了 1 次或多次治疗后出现的不良事件；最常见的是注射部位疼痛（13.0%）和体重增加（12.8%）。大多数参与者（>80%）无注射部位反应。实验室或心电图值、生命体征、锥体外系症状或自杀意念均无临床意义上的变化。在 12 个月的暴露期间，滚动入组参与者的 PANSS 评分持续改善，初治参与者的评分保持稳定。所有参与者的临床总体印象严重度评分保持稳定。
意义/结论：除预期的注射部位反应外，RBP-7000 表现出与利培酮口服制剂相似的有利安全性和耐受性特征。值得注意的是，来自关键研究的参与者的 PANSS 评分持续改善，初治参与者的评分保持稳定。
