University of British Columbia, Vancouver, BC, Canada.
Bipolar and Depressive Disorders Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Int Clin Psychopharmacol. 2020 May;35(3):147-156. doi: 10.1097/YIC.0000000000000307.
This double-blind placebo-controlled, fixed/flexible-dose phase 2 trial assessed the efficacy, safety, and tolerability of cariprazine vs. placebo for depressive episodes associated with bipolar I or II disorder. Primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores (baseline to week 8), and secondary endpoint was mean Clinical Global Impressions-Improvement score (week 8). Patients were randomized (N = 233) 1:1:1 to placebo, 'low-dose' 0.25-0.5 mg/day or 'high-dose' 1.5-3.0 mg/day cariprazine. Adverse events, laboratory results, vital signs, extrapyramidal symptoms, and suicide risk were monitored. Neither cariprazine group significantly separated from placebo in primary (mixed-effect model repeated measures MADRS least-squares mean differences: low-dose = -0.7, P = 0.7408; high-dose = 0.0, P = 0.9961) or secondary efficacy measures. No new safety signals with cariprazine were observed and common treatment-emergent adverse events (≥5% of cariprazine patients and twice the rate of placebo) included insomnia, akathisia, dry mouth, nausea, weight increased, diarrhea, restlessness, vomiting, musculoskeletal stiffness, migraine, and cough. Metabolic and weight changes were generally similar for cariprazine and placebo. Factors that may have affected the outcome of the trial were identified, which helped to inform the design and conduct of subsequent phase 2b/3 clinical trials of cariprazine in bipolar depression.
这项双盲安慰剂对照、固定/灵活剂量的 2 期试验评估了卡利拉嗪与安慰剂在治疗双相 I 或 II 障碍相关抑郁发作中的疗效、安全性和耐受性。主要终点是蒙哥马利-Åsberg 抑郁评定量表（MADRS）总分的变化（基线至第 8 周），次要终点是临床总体印象-改善评分的平均值（第 8 周）。患者以 1:1:1 的比例随机分配（N=233）至安慰剂组、低剂量（0.25-0.5mg/天）组或高剂量（1.5-3.0mg/天）卡利拉嗪组。监测不良事件、实验室结果、生命体征、锥体外系症状和自杀风险。卡利拉嗪组在主要疗效（混合效应模型重复测量 MADRS 最小二乘均数差值：低剂量组=-0.7，P=0.7408；高剂量组=0.0，P=0.9961）或次要疗效测量上均未与安慰剂显著分离。与卡利拉嗪相关的新的安全性信号未被观察到，常见的治疗中出现的不良反应（≥卡利拉嗪患者的 5%且是安慰剂的两倍）包括失眠、静坐不能、口干、恶心、体重增加、腹泻、不安、呕吐、肌肉骨骼僵硬、偏头痛和咳嗽。卡利拉嗪和安慰剂的代谢和体重变化总体相似。确定了可能影响试验结果的因素，这有助于为卡利拉嗪在双相抑郁中的后续 2b/3 期临床试验的设计和实施提供信息。
