Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A
Department of Urology, University Hospital Maastricht, Maastricht, The Netherlands
Urology. 2001 Mar;57(3):414-21. doi: 10.1016/s0090-4295(00)01113-4.
To evaluate the efficacy and tolerability of a new extended-release (ER), once-daily, capsule formulation of tolterodine, relative to placebo and the existing immediate-release (IR), twice-daily, tablet formulation, for treatment of the overactive bladder.
This was a double-blind, multicenter, randomized, placebo-controlled trial. One thousand five hundred twenty-nine patients (81% women) with urinary frequency (eight or more micturitions every 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral therapy with tolterodine ER 4 mg once daily (n = 507), tolterodine IR 2 mg twice daily (n = 514), or placebo (n = 508) for 12 weeks. Efficacy was assessed at the end of the treatment period on the basis of the micturition diary variables. Tolerability and safety were assessed by evaluating the adverse events, electrocardiogram parameters, laboratory values, and treatment withdrawals.
Tolterodine ER 4 mg once daily (P = 0.0001) and tolterodine IR 2 mg twice daily (P = 0.0005) both significantly reduced the mean number of urge incontinence episodes per week compared with placebo. The median reduction in these episodes as a percentage of the baseline values was 71% for tolterodine ER, 60% for tolterodine IR, and 33% for placebo. The ER formulation was 18% more effective than the IR formulation (P <0.05). Treatment with both formulations of tolterodine was also associated with statistically significant improvements in all other micturition diary variables compared with placebo. For both formulations, the mean decreases in micturition frequency (P <0.0079) and pad usage (P <0.0145) were significant, and the mean volume voided per micturition increased (P = 0.0001). The rate of dry mouth (of any severity) was 23% for tolterodine ER, 30% for tolterodine IR, and 8% for placebo. The overall dry mouth rate for patients taking tolterodine ER was 23% lower than for tolterodine IR (P <0.02), and the rate of severe dry mouth in the ER group was only 1.8%. The rates of withdrawal were comparable for the two active groups and the placebo group. No safety concerns were noted.
Tolterodine ER 4 mg once daily is effective and well tolerated in the treatment of overactive bladder with no safety concerns. Tolterodine ER demonstrated an improved efficacy for reducing urge incontinence episodes and a lower frequency of dry mouth compared with the existing IR twice-daily formulation.
评估一种新型的托特罗定缓释胶囊制剂（每日一次）相对于安慰剂以及现有的速释片剂制剂（每日两次）治疗膀胱过度活动症的疗效和耐受性。
这是一项双盲、多中心、随机、安慰剂对照试验。1529例有尿频（每24小时排尿8次或更多）和急迫性尿失禁（每周发作5次或更多）的患者（81%为女性）被随机分为口服托特罗定缓释片4mg每日一次（n = 507）、托特罗定速释片2mg每日两次（n = 514）或安慰剂（n = 508），治疗12周。在治疗期结束时，根据排尿日记变量评估疗效。通过评估不良事件、心电图参数、实验室值和治疗中断情况来评估耐受性和安全性。
与安慰剂相比，托特罗定缓释片4mg每日一次（P = 0.0001）和托特罗定速释片2mg每日两次（P = 0.0005）均显著降低了每周急迫性尿失禁发作的平均次数。这些发作次数相对于基线值的中位数减少百分比，托特罗定缓释片为71%，托特罗定速释片为60%，安慰剂为33%。缓释制剂比速释制剂疗效高18%（P <0.05）。与安慰剂相比，两种托特罗定制剂治疗在所有其他排尿日记变量方面也有统计学显著改善。对于两种制剂，排尿频率的平均降低（P <0.0079）和护垫使用量的平均降低（P <0.0145）均显著，且每次排尿的平均尿量增加（P = 0.0001）。托特罗定缓释片口干（任何严重程度）发生率为23%，托特罗定速释片为30%，安慰剂为8%。服用托特罗定缓释片患者的总体口干发生率比服用托特罗定速释片患者低23%（P <0.02），缓释片组严重口干发生率仅为1.8%。两个活性组和安慰剂组的停药率相当。未发现安全性问题。
托特罗定缓释片4mg每日一次治疗膀胱过度活动症有效且耐受性良好，无安全性问题。与现有的每日两次速释制剂相比，托特罗定缓释片在减少急迫性尿失禁发作方面疗效更佳，口干发生率更低。
