Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ, USA.
Prescott Medical Communications Group, 205 N. Michigan Ave, Suite 3400, Chicago, IL, USA.
Schizophr Res. 2014 Feb;152(2-3):450-7. doi: 10.1016/j.schres.2013.11.041. Epub 2014 Jan 10.
Cariprazine is an orally active and potent D3 and D2 partial agonist with preferential binding to D3 receptors in development for the treatment of schizophrenia and bipolar mania. This study (NCT00694707) evaluated the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.
This study was a multinational, double-blind, randomized, placebo- and active-controlled, fixed-dose trial. Patients were randomized to receive placebo, cariprazine 1.5mg/d, cariprazine 3.0mg/d, cariprazine 4.5mg/d, or risperidone 4.0mg/d (for assay sensitivity) for 6 weeks of double-blind treatment and 2 weeks of safety follow-up. Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total and Global Impressions-Severity of Illness (CGI-S) scores, respectively. Safety parameters included adverse events (AEs), vital signs, laboratory measures, and extrapyramidal symptom (EPS) scales.
Of 732 randomized patients, 64% completed the study. PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5mg/d, 3.0mg/d, and 4.5mg/d (least squares mean difference [LSMD]: -7.6, -8.8, -10.4, respectively; p<0.001; LOCF) and risperidone (-15.1, p<0.001; LOCF); significant improvement on CGI-S was demonstrated for all active treatments (p<0.05). The most frequent cariprazine AEs (≥ 5% and at least twice the rate of the placebo group) were insomnia, extrapyramidal disorder, akathisia, sedation, nausea, dizziness, and constipation. Mean changes in metabolic parameters were small and similar between groups.
The results of this study support the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.
卡利拉嗪是一种具有口服活性和强效的 D3 和 D2 部分激动剂，在开发中优先与 D3 受体结合，用于治疗精神分裂症和双相躁狂。这项研究（NCT00694707）评估了卡利拉嗪在精神分裂症急性加重患者中的疗效和安全性。
这是一项多中心、双盲、随机、安慰剂和活性对照、固定剂量试验。患者被随机分配接受安慰剂、卡利拉嗪 1.5mg/d、卡利拉嗪 3.0mg/d、卡利拉嗪 4.5mg/d 或利培酮 4.0mg/d（用于检测灵敏度），进行 6 周的双盲治疗和 2 周的安全性随访。主要和次要疗效参数分别为阳性和阴性综合征量表（PANSS）总分和总体印象严重程度量表（CGI-S）评分从基线到第 6 周的变化。安全性参数包括不良事件（AE）、生命体征、实验室检查和锥体外系症状（EPS）量表。
在 732 名随机患者中，64%完成了研究。与安慰剂相比，卡利拉嗪 1.5mg/d、3.0mg/d 和 4.5mg/d 在第 6 周时 PANSS 总分改善具有统计学意义（最小二乘均数差值[LSMD]：分别为-7.6、-8.8、-10.4；p<0.001；LOCF）和利培酮（-15.1，p<0.001；LOCF）；所有活性治疗均显示 CGI-S 显著改善（p<0.05）。最常见的卡利拉嗪不良事件（≥5%，且至少是安慰剂组的两倍）为失眠、锥体外系障碍、静坐不能、镇静、恶心、头晕和便秘。各组之间代谢参数的变化较小且相似。
这项研究的结果支持卡利拉嗪在精神分裂症急性加重患者中的疗效和安全性。
