New York University Medical Center, New York, New York.
Serenity Pharmaceuticals LLC, Milford, Pennsylvania.
J Urol. 2018 Sep;200(3):604-611. doi: 10.1016/j.juro.2018.04.050. Epub 2018 Apr 12.
SER120 desmopressin intranasal spray is the first U.S. Food and Drug Administration approved pharmacotherapy for nocturia. We evaluated its efficacy and safety in 2 randomized, double-blind, placebo controlled studies, DB3 and DB4.
A total of 1,333 intent to treat patients 50 years old or older with 2.16 or more nocturic voids per night during a 2-week screening period were randomized equally to SER120 intranasal spray 1.66 or 0.83 mcg, or placebo for a 12-week treatment. Co-primary end points were the mean change from baseline in nocturic episodes per night and the percent of patients with a 50% or greater reduction in mean nocturic episodes per night. Secondary end points were the validated INTU (Impact of Nighttime Urination) quality of life questionnaire in DB4, time to the first nocturic void and the percent of nights with 1 or fewer nocturic voids.
Each SER120 dose showed statistical significance vs placebo for the 2 co-primary end points, including the mean nocturic episodes per night (-1.4 with 0.83 mcg and -1.5 with 1.66 mcg vs -1.2 with placebo, each p <0.0001), the percent of patients with a 50% or greater reduction in mean nocturic episodes per night (37.9% with 0.83 mcg and 48.7% with 1.66 mcg vs 30.3% with placebo, p = 0.0227 and <0.0001, respectively) as well as for all secondary end points in the pooled analyses. The 1.66 mcg dose demonstrated significant improvements in the INTU score (p = 0.0255). The incidence of hyponatremia, defined as serum sodium 125 mmol/l or less regardless of symptoms or less than 130 mmol/l with symptoms, was 1.1%, 0% and 0.2% in the 1.66 and 0.83 mcg, and placebo groups, respectively. Other adverse events were similar across treatment groups.
SER120 demonstrated significant improvements over placebo for co-primary and secondary efficacy end points that corresponded with quality of life improvements. SER120 at each dose had an acceptable safety profile.
SER120 去氨加压素鼻喷雾剂是美国食品和药物管理局批准的第一种用于治疗夜间多尿症的药物。我们在两项随机、双盲、安慰剂对照的研究 DB3 和 DB4 中评估了其疗效和安全性。
共有 1333 名符合入组条件的患者（年龄≥ 50 岁，在两周筛查期内平均每晚有 2.16 次或更多次夜间排尿），随机等分为 SER120 鼻喷雾剂 1.66 或 0.83mcg 组和安慰剂组，进行为期 12 周的治疗。主要疗效终点为夜间排尿次数较基线的平均变化和夜间排尿次数减少 50%或更多的患者比例。次要终点为 DB4 中经过验证的夜间排尿影响（INTU）生活质量问卷，首次夜间排尿时间和夜间排尿次数≤1 的夜间比例。
与安慰剂相比，每种 SER120 剂量在两个主要疗效终点上均具有统计学意义，包括夜间排尿次数的平均值（0.83mcg 组为-1.4 次，1.66mcg 组为-1.5 次，安慰剂组为-1.2 次，均<0.0001），夜间排尿次数减少 50%或更多的患者比例（0.83mcg 组为 37.9%，1.66mcg 组为 48.7%，安慰剂组为 30.3%，p=0.0227 和<0.0001）以及汇总分析中的所有次要终点。1.66mcg 剂量在 INTU 评分上有显著改善（p=0.0255）。低钠血症的发生率（定义为血清钠<125mmol/L，无论有无症状，或<130mmol/L 伴有症状）分别为 1.1%、0%和 0.2%，在 1.66mcg 和 0.83mcg 组以及安慰剂组。其他不良反应在各组之间相似。
SER120 与安慰剂相比，主要疗效终点和次要疗效终点均有显著改善，与生活质量改善相对应。SER120 各剂量组安全性良好。
