Chapple C R, Rechberger T, Al-Shukri S, Meffan P, Everaert K, Huang M, Ridder A
Department of Urology, Royal Hallamshire Hospital, Sheffield, UK.
BJU Int. 2004 Feb;93(3):303-10. doi: 10.1111/j.1464-410x.2004.04606.x.
To assess in a phase 3a trial the efficacy of solifenacin succinate, a once-daily oral antimuscarinic agent in development at 5-mg and 10-mg dosage strengths, for the treatment of overactive bladder (OAB) (Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan) compared with placebo in patients with symptoms of OAB, i.e. urgency, incontinence, and frequency, with additional objectives being to assess the safety and tolerability of solifenacin and to compare the efficacy and safety of solifenacin with tolterodine 2 mg twice daily.
The study was an international, multicentre, randomized, double-blind, tolterodine- and placebo-controlled trial conducted at 98 centres. Adult patients with symptomatic OAB for > or = 3 months were eligible; after a single-blind 2-week placebo run-in period patients were randomized equally to a 12-week double-blind treatment with either tolterodine 2 mg twice daily, placebo, solifenacin 5 mg or 10 mg once daily. Efficacy variables included change from baseline in the mean number of urgency, incontinence and urge incontinence episodes, and change from baseline in voids/24 h and mean volume voided/void.
In all, 1281 patients were enrolled, 1081 randomized and 1077 treated; 1033 were evaluated for efficacy. Compared with placebo, the change from baseline (-1.41, -32.7%) in the mean number of urgency episodes per 24 h was statistically significantly lower with solifenacin 5 mg (-2.85, -51.9%) and 10 mg (-3.07, -54.7%; both P < 0.001), but not with tolterodine (-2.05, -37.9%; P = 0.0511). There was a statistically insignificant decrease in episodes of incontinence with tolterodine (-1.14; P = 0.1122) but a significant decrease in patients treated with solifenacin 5 (-1.42; P = 0.008) and 10 mg (-1.45; P = 0.0038). Compared with placebo (-1.20, -8.1%) the mean number of voids/24 h was significantly lower in patients receiving tolterodine (-1.88, -15%; P = 0.0145), solifenacin 5 (-2.19, -17%) and 10 mg (-2.61, -20%; both P < 0.001). The mean volume voided/void was also significantly higher with all three active treatments (P < 0.001). Solifenacin was well tolerated; compared with placebo (4.9%), dry mouth (the most common side-effect), mostly mild, was reported in 18.6% of patients receiving tolterodine, 14.0% receiving 5 mg and 21.3% receiving 10 mg solifenacin.
Solifenacin 5 and 10 mg once daily improved urgency and other symptoms of OAB, and was associated with an acceptable level of anticholinergic side-effects. Solifenacin demonstrated significantly favourable efficacy to side-effect ratio in treating symptomatic OAB.
在一项3a期试验中评估琥珀酸索利那新（一种每日一次口服的抗毒蕈碱药物，正处于研发阶段，剂量分别为5毫克和10毫克）治疗膀胱过度活动症（OAB）（由日本东京山之内制药有限公司研发）的疗效，将其与安慰剂相比较，受试对象为有OAB症状（即尿急、尿失禁和尿频）的患者，另外的目的是评估索利那新的安全性和耐受性，并将索利那新与每日两次服用2毫克托特罗定的疗效和安全性进行比较。
该研究是一项在98个中心进行的国际性、多中心、随机、双盲、以托特罗定和安慰剂为对照的试验。有症状的OAB持续≥3个月的成年患者符合入选标准；在经过为期2周的单盲安慰剂导入期后，患者被等比例随机分为接受以下治疗的4组，进行为期12周的双盲治疗：每日两次服用2毫克托特罗定、安慰剂、每日一次服用5毫克索利那新或10毫克索利那新。疗效变量包括尿急、尿失禁和急迫性尿失禁发作的平均次数相对于基线的变化，以及每24小时排尿次数和每次平均尿量相对于基线的变化。
总共1281例患者入组，1081例被随机分组，1077例接受治疗；1033例接受了疗效评估。与安慰剂相比，每日24小时尿急发作的平均次数相对于基线的变化（-1.41，-32.7%），服用5毫克（-2.85，-51.9%）和10毫克（-3.07，-54.7%；P均<0.001）索利那新的患者降低幅度有统计学显著意义，而服用托特罗定的患者（-2.05，-37.9%；P = 0.0511）则无显著意义。托特罗定治疗组尿失禁发作次数有统计学意义不显著的降低（-1.14；P = 0.1122），而服用5毫克（-1.42；P = 0.008）和10毫克（-1.45；P = 0.0038）索利那新的患者有显著降低。与安慰剂组（-1.20，-8.1%）相比，接受托特罗定（-1.88，-15%；P = 0.0145）、5毫克（-2.19，-17%）和10毫克（-2.61，-20%；P均<0.001）索利那新治疗的患者每24小时排尿次数显著减少。三种活性治疗组每次平均尿量也显著增加（P<0.001）。索利那新耐受性良好；与安慰剂组（4.9%）相比，口干（最常见副作用，大多为轻度）在接受托特罗定治疗的患者中报告率为18.6%，接受5毫克索利那新治疗的患者中为14.0%，接受10毫克索利那新治疗的患者中为21.3%。
每日一次服用5毫克和10毫克索利那新可改善OAB的尿急及其他症状，且抗胆碱能副作用处于可接受水平。索利那新在治疗有症状的OAB方面显示出显著良好的疗效副作用比。
