Durgam Suresh, Earley Willie, Li Rui, Li Dayong, Lu Kaifeng, Laszlovszky István, Fleischhacker W Wolfgang, Nasrallah Henry A
Allergan, Inc., Jersey City, NJ, USA.
Allergan, Inc., Jersey City, NJ, USA.
Schizophr Res. 2016 Oct;176(2-3):264-271. doi: 10.1016/j.schres.2016.06.030. Epub 2016 Jul 15.
Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3-9mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9mg/d) or placebo for double-blind treatment (up to 72weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n=99) or cariprazine (n=101). Time to relapse was significantly longer in cariprazine- versus placebo-treated patients (P=.0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI]=0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥10% of patients during open-label treatment; there were no cariprazine adverse events ≥10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060.
卡立普嗪是一种对多巴胺D3受体具有优先选择性的D3/D2受体部分激动剂，已在精神分裂症的随机对照试验中证明了其疗效。这项多中心、随机、双盲、安慰剂对照、平行组研究评估了卡立普嗪对精神分裂症成年患者预防复发的疗效、安全性和耐受性；研究总时长最长可达97周。在为期20周的开放标签治疗期间，使用3 - 9mg/d的卡立普嗪治疗/稳定精神分裂症症状，该开放标签治疗包括一个为期8周的灵活剂量导入期和一个为期12周的固定剂量稳定期。完成开放标签治疗的病情稳定患者可随机分配至继续使用卡立普嗪（3、6或9mg/d）或安慰剂进行双盲治疗（最长72周）。主要疗效参数为复发时间（症状评分恶化、精神科住院、攻击/暴力行为或自杀风险）；实施了临床措施以确保在即将复发时的安全性。共有264/765例患者完成了开放标签治疗；200例符合条件的患者被随机分配至双盲安慰剂组（n = 99）或卡立普嗪组（n = 101）。与安慰剂治疗的患者相比，卡立普嗪治疗的患者复发时间显著更长（P = .0010，对数秩检验）。卡立普嗪治疗组24.8%的患者和安慰剂治疗组47.5%的患者出现复发（风险比[95%置信区间]=0.45 [0.28, 0.73]）。在开放标签治疗期间，≥10%的患者报告出现静坐不能（19.2%）、失眠（14.4%）和头痛（12.0%）；在双盲治疗期间，没有出现≥10%的卡立普嗪不良事件。长期使用卡立普嗪治疗在预防精神分裂症患者复发方面显著优于安慰剂。本研究中的长期安全性概况与先前卡立普嗪临床试验中观察到的安全性概况一致。ClinicalTrials.gov标识符：NCT01412060。
