Safety and tolerability of tolterodine for the treatment of overactive bladder in men with bladder outlet obstruction. A randomized, double-blind, placebo- and propiverine-controlled trial of the novel antimuscarinic agent imidafenacin in Japanese patients with overactive bladder. Time to onset of improvement in symptoms of overactive bladder using antimuscarinic treatment Do patient characteristics predict responsiveness to treatment of overactive bladder with antimuscarinic agents? The efficacy and safety of mirabegron compared with solifenacin in overactive bladder patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy: results of a noninferiority, randomized, phase IIIb trial Tolterodine extended release with or without tamsulosin in men with lower urinary tract symptoms including overactive bladder symptoms: effects of prostate size. Is there a synergistic effect of topical oestrogens when administered with antimuscarinics in the treatment of symptomatic detrusor overactivity? Naftopidil and propiverine hydrochloride for treatment of male lower urinary tract symptoms suggestive of benign prostatic hyperplasia and concomitant overactive bladder: A prospective randomized controlled study Safety and efficacy of flexible-dose fesoterodine in British subjects with overactive bladder: insights into factors associated with dose escalation Comparison of two selective muscarinic receptor antagonists (solifenacin and darifenacin) in women with overactive bladder--the SOLIDAR study. Randomized, double‐blind, placebo‐ and propiverine‐controlled trial of the once‐daily antimuscarinic agent solifenacin in Japanese patients with overactive bladder Trospium chloride improves overactive bladder symptoms: a multicenter phase III trial. Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE). Combination treatment with propiverine hydrochloride plus doxazosin controlled release gastrointestinal therapeutic system formulation for overactive bladder and coexisting benign prostatic obstruction: a prospective, randomized, controlled multicenter study. Tolterodine extended release improves overactive bladder symptoms in men with overactive bladder and nocturia. Cizolirtine citrate is safe and effective for treating urinary incontinence secondary to overactive bladder: a phase 2 proof-of-concept study. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a β(3)-adrenoceptor agonist, in overactive bladder. OnabotulinumtoxinA improves health-related quality of life in patients with urinary incontinence due to idiopathic overactive bladder: a 36-week, double-blind, placebo-controlled, randomized, dose-ranging trial. A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial. Treatment with solifenacin increases warning time and improves symptoms of overactive bladder: results from VENUS, a randomized, double-blind, placebo-controlled trial. The association of diet and other lifestyle factors with the onset of overactive bladder: a longitudinal study in men. Solifenacin as add-on therapy for overactive bladder symptoms in men treated for lower urinary tract symptoms--ASSIST, randomized controlled study. Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (Symphony).
PURPOSE Antimuscarinic therapy for men with OAB and BOO is perceived as a potential risk for urinary retention . Using pressure flow urodynamics , we evaluated the safety of tolterodine vs placebo in men with OAB and BOO . MATERIAL S AND METHODS Men ( older than 40 years ) with BOO and confirmed detrusor overactivity were r and omized to tolterodine ( 2 mg twice daily in 149 ) or placebo ( in 72 ) for 12 weeks . Primary end points were Qmax and pdetQmax . RESULTS Median treatment differences in Qmax ( -0.7 ml per second , 95 % CI -1.6 to 0.4 ) and pdetQmax ( -7 cm H2O , 95 % CI -3 to 11 ) were comparable . Tolterodine significantly reduced the BOOI vs placebo ( -9 vs 0 , p < 0.02 ) . There were significant treatment differences in volume to first detrusor contraction ( + 59 ml , 95 % CI 19 - 100 ) and maximum cystometric capacity ( + 67 ml , 95 % CI 35 - 103 ) , favoring tolterodine over placebo ( p < 0.003 ) . Change in PVR was significantly greater among patients treated with tolterodine ( + 25 ml ) than placebo ( 0 ml , p < 0.004 ) . There were no significant between-group differences in the incidence of adverse events . Urinary retention was reported by 1 patient treated with placebo . CONCLUSIONS Tolterodine did not adversely affect urinary function in men with OAB and BOO .  Urinary flow rate was unaltered , and there was no evidence of clinical ly meaningful changes in voiding pressure and PVR or urinary retention .  Tolterodine was well tolerated . These results suggest that antimuscarinics can be safely administered in men with BOO OBJECTIVES To compare the efficacy and tolerability of imidafenacin , a novel antimuscarinic agent , with propiverine and a placebo in Japanese patients with overactive bladder ( OAB ) . METHODS Men and women having OAB symptoms were r and omized to double-blind treatment with 0.1 mg of imidafenacin twice daily , 20 mg of propiverine once daily , or a placebo for 12 weeks , and assessed for efficacy and safety . RESULTS Overall , 781 patients were r and omized to imidafenacin ( 324 ) , propiverine ( 310 ) , or a placebo ( 147 ) . After 12 weeks of treatment , a significantly larger reduction in the mean number of incontinence episodes was observed in the imidafenacin group than in the placebo group ( P < 0.0001 ) . The non-inferiority of imidafenacin compared with propiverine was confirmed for the reduction in using incontinence episodes ( P = 0.0014 , non-inferiority margin : 14.5 % ) . Imidafenacin was well tolerated . The incidence of adverse events with imidafenacin was significantly lower than with propiverine ( P = 0.0101 ) . Dry mouth , the most common adverse event , was significantly more common in the propiverine group than in the imidafenacin group ( P = 0.0302 ) . There were no significant increases in either the imidafenacin or placebo group in the mean QTc interval , whereas there was a significant increase in the mean QTc interval in the propiverine group ( P < 0.0001 ) , but there were no clinical arrhythmia and clinical arrhythmic events in any of the treatment groups . CONCLUSIONS The novel antimuscarinic agent imidafenacin at a dose of 0.1 mg twice daily was not inferior to propiverine for the reduction of incontinence episodes , and well tolerated for the treatment of OAB symptoms To evaluate the time to onset of statistically significant and clinical ly meaningful effects of trospium chloride in patients with an overactive bladder ( OAB ) OBJECTIVE To determine clinical and demographic characteristics associated with antimuscarinic treatment response using a regression model . METHODS Adults with overactive bladder ( OAB ) symptoms for > 3 months and ≥ 1 urgency urinary incontinence ( UUI ) episode and ≥ 8 micturitions per 24 hours at baseline were r and omized to fesoterodine ( 8 mg ) , tolterodine extended-release ( 4 mg ) , or placebo in two 12-week , double-blind , head-to-head studies . Fesoterodine-treated patients received 4 mg/d during the first week and 8 mg/d thereafter . Patients completed 3-day bladder diaries and the Overactive Bladder Question naire at baseline and week 12 . Pooled data for changes from baseline to week 12 in winsorized UUI episodes , micturitions , and urgency episodes per 24 hours and Overactive Bladder Question naire Symptom Bother and health-related quality of life scores were analyzed posthoc using a regression model that selects outcome predictors from baseline values and patient characteristics while retaining baseline values and treatment , with stepwise inclusion of significant covariates and assessment of treatment interactions . Logistic regression was used for analysis of diary-dry rates . RESULTS Younger age , lack of previous antimuscarinic treatment , shorter duration of OAB diagnosis , and female gender were common predictors of larger changes in outcomes from baseline to week 12 . Baseline measures often interacted with treatment , such that poorer baseline outcomes were predictive of larger treatment differences . Longer duration since OAB diagnosis predicted greater treatment differences for UUI episodes and in diary-dry rate , and increased age predicted greater treatment differences for micturitions . CONCLUSION Symptom severity and duration , age , gender , and previous antimuscarinic pharmacotherapy impact the response to antimuscarinic treatment Objective : To compare the efficacy and safety of mirabegron 50 mg and solifenacin 5 mg in overactive bladder ( OAB ) patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy . Patients and methods : This r and omized , double-blind , phase IIIb , noninferiority study , enrolled male and female patients aged ⩾18 years old , with symptoms of OAB for ⩾3 months , who were dissatisfied with their previous antimuscarinic drug due to lack of efficacy . A total of 1887 patients were r and omized to receive mirabegron 50 mg ( n = 943 ) or solifenacin 5 mg ( n = 944 ) daily for 12 weeks . The primary efficacy endpoint was change from baseline to end of treatment in mean number of micturitions/24 h. Noninferiority was confirmed if the lower limit of the two-sided 95 % confidence interval ( CI ) for the treatment difference between solifenacin and mirabegron was > −0.20 . Secondary efficacy endpoints , which included change from baseline in mean number of incontinence episodes/24 h , urgency incontinence episodes/24 h , urgency episodes ( grade 3 or 4)/24 h and nocturia episodes/24 h , were analyzed using analysis of covariance . Results : For the primary endpoint , adjusted mean treatment difference ( 95 % CI ) in mean number of micturitions/24 h was −0.18 ( −0.42 , 0.06 ) and therefore noninferiority of mirabegron to solifenacin was not demonstrated . Both treatments demonstrated clinical ly meaningful reductions in efficacy variables and were well tolerated , with a lower incidence of dry mouth with mirabegron . Conclusions : Noninferiority of mirabegron compared with solifenacin for reduction in micturition frequency could not be demonstrated in this population of OAB patients who were dissatisfied with previous antimuscarinic therapy due to lack of efficacy . Both mirabegron and solifenacin improved key OAB symptoms with no statistically significant differences observed between the two treatments . Both drugs were well tolerated BACKGROUND Some men with lower urinary tract symptoms ( LUTS ) including overactive bladder ( OAB ) symptoms may benefit from antimuscarinic therapy , with or without an alpha-adrenergic antagonist . OBJECTIVES To evaluate the safety and efficacy of tolterodine extended release ( ER ) , tamsulosin , or tolterodine ER+tamsulosin in men meeting symptom entry criteria for OAB and prostatic enlargement trials , stratified by prostate size . DESIGN , SETTING , AND PARTICIPANTS Subjects with an International Prostate Symptom Score ( IPSS ) > or=12 ; frequency and urgency , with or without urgency urinary incontinence ; postvoid residual volume ( PVR ) < 200 mL ; and maximum urinary flow rate ( Q(max ) ) > 5 mL/s were r and omized to receive placebo , tolterodine ER ( 4 mg ) , tamsulosin ( 0.4 mg ) , or tolterodine ER+tamsulosin for 12 wk . Data were stratified by median baseline prostate volume ( < 29 mL vs > or=29 mL ) . MEASUREMENTS Endpoints included week 12 changes in bladder diary variables , IPSS scores , and safety variables . RESULTS AND LIMITATIONS Among men with larger prostates , tolterodine ER+tamsulosin significantly improved frequency ( p=0.001 ) ; urgency ( p=0.006 ) ; and IPSS total ( p=0.001 ) , storage ( p<0.001 ) , and voiding scores ( p<0.013 ) . Tamsulosin significantly improved IPSS voiding scores ( p=0.030 ) . Among men with smaller prostates , tolterodine ER significantly improved frequency ( p=0.016 ) , UUI episodes ( p=0.036 ) , and IPSS storage scores ( p=0.005 ) . Tolterodine ER+tamsulosin significantly improved frequency ( p=0.001 ) and IPSS storage scores ( p=0.018 ) . Tamsulosin significantly improved nocturnal frequency ( p=0.038 ) and IPSS voiding ( p=0.036 ) and total scores ( p=0.044 ) . There were no clinical ly or statistically significant changes in Q(max ) or PVR ; incidence of acute urinary retention ( AUR ) was low in all groups ( < or=2 % ) . CONCLUSIONS Men with smaller prostates and moderate-to-severe LUTS including OAB symptoms benefited from tolterodine ER . Therapy with tolterodine ER+tamsulosin was effective regardless of prostate size . Tolterodine ER , with or without tamsulosin , was well tolerated and not associated with increased incidence of AUR BACKGROUND No authors have investigated whether the administration of local oestrogens in addition to antimuscarinics could have a synergistic effect in the therapy of overactive bladder ( OAB ) . OBJECTIVES To compare the efficacy of antimuscarinics alone versus antimuscarinics in combination with local oestrogens for OAB ; to verify whether risk factors for lower antimuscarinic efficacy can be overcome by the concomitant use of local oestrogens . DESIGN , SETTING , AND PARTICIPANTS Some 229 postmenopausal women with symptomatic urodynamically proven detrusor overactivity were prospect ively enrolled at a tertiary level urogynaecology centre and divided into two groups . INTERVENTION Women in group 1 ( n=129 ) were prescribed tolterodine extended release ( ER ) 4 mg once daily ; women in group 2 ( n=100 ) were prescribed both tolterodine ER 4 mg and concomitant oestriol cream application once daily . MEASUREMENTS All women underwent clinical evaluation and urodynamics in accordance with the Good Urodynamic Practice s Guidelines . After 12 wk of treatment the two groups were compared in terms of subjective efficacy for OAB symptom improvement using a three-point scale . Nonresponders were compared to the patients who improved or were cured in order to identify risk factors for resistance to therapy . RESULTS AND LIMITATIONS There was no significant difference between the two groups in terms of efficacy of therapy : 80.6 % in group 1 versus 82 % in group 2 ( p=0.86 ) . Patients with urodynamically proven detrusor overactivity ( DO ) occurring during provocative manoeuvres and patients with coital incontinence during orgasm reported a higher failure rate both in the overall study population and in group 2 . A possible limitation of the study is the nonr and omised design . CONCLUSIONS No synergistic effect of local oestrogens and antimuscarinics in the treatment of OAB was found . Antimuscarinic treatment has lower cure rates in women with symptomatic DO complaining of incontinence at orgasm or in patients with DO following provocative manoeuvres . The association of local oestrogens does not influence the role of the two mentioned risk factors Objective . To assess the efficacy and safety of propiverine hydrochloride ( antimuscarinic ) , naftopidil ( α1-adrenoceptor antagonist ) or both in patients with male lower urinary tract symptoms ( LUTS ) suggestive of benign prostatic hyperplasia and concomitant overactive bladder ( OAB ) . Material and methods . Men aged at least 50 years who had a total International Prostate Symptom Score ( IPSS ) of 8 or higher and bladder dairy documenting micturition frequency ( more than eight micturitions/24 h ) and urgency ( more than one episode/24 h ) , with or without urgency urinary incontinence were r and omized into three groups : group N , naftopidil ( 50 mg once daily ) only ; group P , propiverine hydrochloride ( 20 mg once daily ) ; and group NP , naftopidil ( 50 mg once daily ) plus propiverine hydrochloride ( 20 mg once daily ) for a 4-week treatment regimen . Results . A total of 66 men , including 20 in group N , 23 in group P and 23 in group NP , were treated and 58 ( 87.9 % ) completed the 4 weeks of treatment . IPSS improved significantly in groups N and NP . Urinary frequency improved significantly in groups P and NP . Postvoid residual urine volume increased significantly in groups P and NP . Significant improvements in urgency episodes were noted in each group . One patient in group P required catheterization owing to acute urinary retention and another stopped medication because of difficulty in voiding . Conclusion . These results suggest that each treatment showed effectiveness for male LUTS with OAB . However , there are some possibilities of adverse effects with propiverine hydrochloride monotherapy Introduction and hypothesisThis study evaluated the efficacy and safety of flexible-dose fesoterodine and factors associated with dose escalation in subjects with overactive bladder ( OAB ) . Methods In this 12-week , open-label study , 331 adults with OAB symptoms for ≥3 months , ≥8 micturitions and ≥3 urgency episodes per 24 h and who reported at least “ some moderate ” bladder-related problems were treated with fesoterodine 4 mg once daily for 4 weeks , with the option to escalate to 8 mg for the remaining 8 weeks based on discussion of efficacy and tolerability with the investigator . Factors influencing dose escalation were identified using stepwise logistic regression . Efficacy was assessed via 3-day bladder diaries and patient-reported outcomes . Results Of the subjects , 59 % dose escalated at week 4 ; 93 % of escalators cited insufficient clinical response . The decision to escalate was most often made by the subject ( alone or with the investigator ) . Improvements from baseline were observed in diary and patient-reported outcomes at weeks 4 and 12 . Smaller improvements in micturition frequency and worse bladder-related problems at week 4 were significantly associated with increased likelihood of dose escalation ; baseline micturition frequency , age , sex , body mass index , antimuscarinic-associated adverse events and OAB symptom duration were not . Non-escalators had greater improvement from baseline to week 4 than escalators ; by week 12 , improvement was similar among escalators and non-escalators . Fesoterodine was well tolerated . Conclusions Treatment with flexible-dose fesoterodine  improved bladder diary and patient-reported outcomes . Lower clinical response was related to dose escalation ; after escalation , response in escalators approached that of non-escalators Overactive bladder ( OAB ) is a common , often debilitating , condition defined as urgency and urge incontinence , usually with frequency and nocturia . The use of muscarinic receptor antagonists are the mainstay of treatment , but their non-selectivity can result in unacceptable adverse effects that limit their usefulness . The purpose of this study was to evaluate 2 of the newer antimuscarinic agents , solifenacin and darifenacin , which demonstrate greater selectivity , in order to compare their tolerance and effectiveness . This was a multicentre , prospect i ve , r and omised , comparative ( 1:1 ) open-label study conducted in 4 centres comprising Slovenian gynaecologists and urologists . A total of 77 female patients with OAB were enrolled who received either solifenacin 5 mg or darifenacin 7.5 mg once daily . Study measurements consisted of changes in OAB symptoms and quality of life ( QOL ) evaluations after 1 and 3 months of treatment . Both treatment groups showing a reduction in all OAB symptoms but with no notable difference being seen between the 2 groups . Solifenacin though showed statistically greater improvements in QOL , better overall treatment satisfaction , and a decreased incidence of dry mouth after 3 months of treatment compared to the darifenacin group . This study demonstrates interesting initial results and indicates that these 2 drugs have a different profile that may confer an advantage to patients , but further method ologically rigorous studies comparing the use of solifenacin and darifenacin in OAB are required to establish the differences between these drugs over longer periods of treatment To compare solifenacin succinate ( 5 and 10 mg once‐daily ) to placebo and propiverine hydrochloride ( 20 mg once‐daily ) , respectively , in Japanese patients with overactive bladder syndrome ( OAB ) PURPOSE Trospium chloride is an anticholinergic agent with predominantly peripheral nonselective antimuscarinic activity lacking central nervous system effects . It has no known drug-drug interactions , an advantage for patients taking many medications . Because these qualities may provide added benefit when treating patients with symptoms associated with overactive bladder ( OAB ) and urge incontinence , we studied the effectiveness of trospium in treating these conditions . MATERIAL S AND METHODS Patients with OAB with urge incontinence were r and omized 1:1 to 20 mg trospium twice daily or placebo in this 12-week , multicenter , parallel , double-blind , placebo controlled trial . Dual primary end points were change in average number of toilet voids and change in urge incontinent episodes per 24 hours . Secondary efficacy variables were change in average of volume per void , voiding urge severity , urinations during day and night , time to onset of action and change in Incontinence Impact Question naire . RESULTS A total of 523 patients were entered at 51 sites .  Trospium significantly decreased average frequency of toilet voids and urge incontinent episodes compared to placebo . It significantly increased average volume per void , and decreased average urge severity and daytime frequency . All effects occurred by week 1 and all were sustained throughout the study . Nocturnal frequency decreased significantly by week 4 and Incontinence Impact Question naire scores improved at week 12 . Trospium was well tolerated . CONCLUSIONS Trospium was found to have sustained effectiveness beginning at the end of week 1 in decreasing the number of voids , urge incontinent episodes , total daily micturitions and urge severity , and in increasing volume per void . It also improved symptoms of OAB and quality of life BACKGROUND Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder ( OAB ) and is often difficult to treat with antimuscarinic monotherapy . OBJECTIVE To evaluate the efficacy and the safety and tolerability of combination ( solifenacin 5 mg and mirabegron 50 mg ) versus solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4 wk of solifenacin 5 mg . DESIGN , SETTING , AND PARTICIPANTS OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-wk single-blind run-in were r and omised 1:1:1 to double-blind daily combination or solifenacin 5 or 10 mg for 12 wk . Patients receiving the combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4 . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was a change from baseline to end of treatment ( EOT ) in the mean number of incontinence episodes per 24h ( stratified rank analysis of covariance [ ANCOVA ] ) . Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h ( ANCOVA ) and number of incontinence episodes noted in a 3-d diary at EOT ( mixed-effects Poisson regression ) . A trial ( BESIDE ) comparing combination treatment ( solifenacin plus mirabegron ) with one treatment alone ( solifenacin ) tested the superiority of combination versus solifenacin 5 mg , noninferiority ( and potential superiority ) of combination versus solifenacin 10 mg ( key secondary end points ) , and the safety and tolerability of combination therapy versus solifenacin monotherapy . RESULTS AND LIMITATIONS A total of 2174 patients were r and omised to combination ( n=727 ) , solifenacin 5 mg ( n=728 ) , or solifenacin 10 mg ( n=719 ) . At EOT , combination was superior to solifenacin 5 mg , with significant improvements in daily incontinence ( p=0.001 ) , daily micturitions ( p<0.001 ) , and incontinence noted in a 3-d diary ( p=0.014 ) . Combination was noninferior to solifenacin 10 mg for key secondary end points and superior to solifenacin 10 mg for improving daily micturitions . All treatments were well tolerated . CONCLUSIONS Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms versus solifenacin 5 or 10 mg , and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg . PATIENT SUMMARY In this 12-wk study , overactive bladder patients who remained incontinent despite initial solifenacin 5 mg treatment received additional treatment with mirabegron 50 mg . Combining mirabegron 50 mg with solifenacin 5 mg was superior to solifenacin 5 mg alone in improving symptoms of incontinence and frequent urination , and it was well tolerated . TRIAL REGISTRATION Clinical Trials.gov NCT01908829 PURPOSE We evaluated the efficacy and safety of a therapeutic modality involving propiverine combined with doxazosin in patients with overactive bladder ( OAB ) and benign prostatic obstruction . MATERIAL S AND METHODS Men 50 years or older with OAB symptoms and urodynamically proven bladder outlet obstruction ( Abrams-Griffith score greater than 20 ) were r and omized ( 1:2 ) into 2 groups , namely group 1-doxazosin controlled release gastrointestinal therapeutic system formulation ( 4 mg once daily ) only and group 2-propiverine hydrochloride ( 20 mg once daily ) plus doxazosin controlled release gastrointestinal therapeutic system formulation for an 8-week treatment regimen . RESULTS A total of 211 men , including 69 in group 1 and 142 in group 2 , were treated and 198 ( 93.8 % ) completed the 8 weeks of treatment . Significant improvements were noted in each group after treatment in urinary frequency , maximum flow rate , average micturition volume and International Prostate Symptom Score . Compared with group 1 improvement rates with regard to urinary frequency ( 23.5 % vs 14.3 % , p = 0.004 ) , average micturition volume ( 32.3 % vs 19.2 % , p = 0.004 ) , and storage ( 41.3 % vs 32.6 % , p = 0.029 ) and urgency ( p = 0.019 ) International Prostate Symptom Score symptoms were more significant in group 2 . Post-void residual urine was found to be significantly increased only in group 2 but this was not accompanied by urinary retention . Patient satisfaction rates were found to be significantly higher in group 2 than in group 1 ( p = 0.002 ) . Overall adverse event rates were higher in group 2 ( p = 0.002 ) , although discontinuation rates and discontinuation rates due to adverse events were not different between the 2 groups . CONCLUSIONS This study reveals that combination therapy consisting of alpha1-adrenoceptor antagonists with antimuscarinics represents an effective and relatively safe treatment modality in select patients with OAB coexisting with benign prostatic obstruction OBJECTIVES To evaluate the efficacy and safety of nighttime dosing with tolterodine extended release ( TER ) in men with overactive bladder ( OAB ) and nocturia . METHODS This was a post hoc analysis of data from two 12-week , double-blind , placebo-controlled trials of nighttime ( < 4 hours before bedtime ) TER ( 4 mg daily ) dosing . Men with a mean micturition frequency of eight or more times in 24 hours , including a mean of 2.5 or more nocturia episodes/night , were included . For each micturition , patients used 7-day diaries to record urinary urgency on a 5-point urgency rating scale ( 1 , none ; 2 , mild ; 3 , moderate ; 4 , severe ; 5 , urgency urinary incontinence ) . Micturitions were analyzed post hoc by urgency rating categories : total ( 1 to 5 ) , non-OAB ( 1 to 2 ) , OAB ( 3 to 5 ) , and severe OAB ( 4 to 5 ) . Adverse events were recorded throughout the study . RESULTS A total of 745 men ( mean age 64 years ) were r and omized to placebo ( n = 374 ) or TER ( n = 371 ) . Of the 745 men , 73 % reported no incontinence episodes in a 7-day diary at baseline . At week 12 , the weekly values for nighttime severe OAB micturitions and 24-hour and daytime total , OAB , and severe OAB micturitions were significantly reduced in the TER group versus the placebo group . The TER-treated men also reported a significant reduction in the mean urgency rating versus placebo . Adverse events associated with TER were low and comparable to those in the placebo group , with the exception of dry mouth ( 11 % versus 4 % ) . Withdrawals because of adverse events were infrequent ( 3 % TER , 4 % placebo ) . Five men were withdrawn for symptoms suggestive of urinary retention ( 3 TER , 2 placebo ) . CONCLUSIONS Nighttime TER dosing reduced urgency-related micturitions and was well tolerated in men with OAB and nocturia BACKGROUND Antimuscarinic agents currently dominate medical treatment for urinary incontinence secondary to overactive bladder ( OAB ) . Alternatives to improve their risk-benefit ratio are welcomed . OBJECTIVE To demonstrate the efficacy and safety of oral cizolirtine citrate in this indication . DESIGN , SETTING , AND PARTICIPANTS A r and omised , double-blind , placebo- and active-controlled , phase 2 multicentre clinical trial performed by urologists or gynaecologists at referral centres . A sample was composed of 135 out patients with signs of lower urinary tract dysfunction and urodynamically documented detrusor overactivity ; 20 patients left the study prematurely , chiefly ( n=10 ) because of adverse events . INTERVENTION Allocation to treatments was asymmetrical ( 2:2:1 ) to cizolirtine citrate 800 mg/d , placebo , or oxybutynin 15 mg/d . Treatments were given for 12 wk . MEASUREMENTS Efficacy measures included a bladder diary , filling- and voiding-phase urodynamic evaluations , and measure of quality of life ( QoL ) . Adverse events were systematic ally recorded . Statistical procedures included analysis of covariance , chi(2 ) tests , and calculation of 95 % confidence intervals . RESULTS AND LIMITATIONS Most patients ( 92.6 % ) were female , and their mean age was 51.8 yr .  Bladder diary variables improved significantly with active drug over placebo : The average number of voidings per 24 h was reduced by 33.4 % , 17.0 % , and 34.3 % ( p=0.001 ) in the cizolirtine citrate , placebo , and oxybutynin groups , respectively . The mean estimated voided volume per voluntary micturition increased by 17.8 % , 0 % , and 14.5 % ( p=0.002 ) in the cizolirtine citrate , placebo , and oxybutynin groups , respectively . The proportions of patients achieving fewer than eight voidings per 24 h , complete dryness , or both were also superior with active drugs over placebo . Only cizolirtine showed significant superiority over placebo to improve urodynamic parameters , although the asymmetrical allocation played against oxybutynin in the inferences . Cizolirtine citrate caused fewer antimuscarinic but more gastrointestinal ( nausea ) and neurologic ( headache and vertigo ) adverse events than oxybutynin . CONCLUSIONS Cizolirtine citrate is a promising agent in the treatment of OAB with urinary incontinence BACKGROUND Despite several antimuscarinic treatment options for overactive bladder ( OAB ) , there is still a need for distinct treatment approaches to manage this condition . Mirabegron , a β(3)-adrenoceptor agonist , has demonstrated efficacy and tolerability for up to 12 wk in phase 3 trials . OBJECTIVE To assess the 12-mo safety and efficacy of mirabegron . DESIGN , SETTING , AND PARTICIPANTS Patients ≥ 18 yr of age with OAB symptoms for ≥ 3 mo . INTERVENTIONS After a 2-wk single-blind placebo run-in , patients with eight or more micturitions per 24h and three or more urgency episodes in a 3-d micturition diary were r and omized 1:1:1 to once-daily mirabegron 50 mg , mirabegron 100 mg , or tolterodine extended release ( ER ) 4 mg for 12 mo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary variable : incidence and severity of treatment-emergent AEs ( TEAEs ) . Secondary variables : change from baseline at months 1 , 3 , 6 , 9 , and 12 in key OAB symptoms . RESULTS AND LIMITATIONS A total of 812 , 820 , and 812 patients  received mirabegron 50 mg , mirabegron 100 mg , and tolterodine ER 4 mg , respectively . Baseline demographic and OAB characteristics were similar across groups . TEAEs were reported in 59.7 % , 61.3 % , and 62.6 % of patients , respectively ; most were mild or moderate . Serious TEAEs were reported in 5.2 % , 6.2 % , and 5.4 % of patients , respectively . The most common TEAEs were similar across groups . Dry mouth was reported by 2.8 % , 2.3 % , and 8.6 % of patients , respectively . Adjusted mean changes from baseline to final visit in morning systolic blood pressure were 0.2 , 0.4 , and -0.5 mm Hg for mirabegron 50 mg , 100 mg , and tolterodine ER 4 mg , respectively . Mirabegron and the active control , tolterodine , improved key OAB symptoms from the first measured time point of 4 wk , and efficacy was maintained throughout the 12-mo treatment period . The study was not placebo controlled , which was a limitation . CONCLUSIONS The safety and tolerability of mirabegron was established over 1 yr , with sustained efficacy observed over this treatment period . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00688688 BACKGROUND Patients with urgency urinary incontinence ( UUI ) due to overactive bladder ( OAB ) refractory to oral antimuscarinics have limited therapeutic options . OnabotulinumtoxinA appears to be an effective new treatment . OBJECTIVE Assess disease-specific quality -of-life outcomes and general health-related quality -of-life ( HRQOL ) outcomes following treatment with onabotulinumtoxinA in patients with idiopathic OAB and UUI inadequately managed with antimuscarinics . DESIGN , SETTING , AND PARTICIPANTS A phase 2 , r and omized , double-blind , placebo-controlled , dose-ranging study conducted at 40 sites from July 2005 to June 2008 with 313 patients ( 288 females ) with idiopathic OAB experiencing eight or more UUI episodes per week and eight or more micturitions per day at baseline , with follow-up of 36 wk . INTERVENTION Intradetrusor onabotulinumtoxinA ( 50 U , 100 U , 150 U , 200 U , or 300 U ) or placebo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS HRQOL was assessed using the urinary Incontinence-Specific Quality -of-Life Instrument ( I-QOL ) , the King 's Health Question naire ( KHQ ) symptom component , and the Medical Outcomes Study 36-Item Short-Form Health Survey . Descriptive statistics were used for absolute scores/changes from baseline . Within-group changes from baseline were assessed using paired t tests . Change from baseline for each onabotulinumtoxinA group compared with placebo was analyzed using an analysis of covariance model . RESULTS AND LIMITATIONS OnabotulinumtoxinA treatment at doses≥100 U produced significantly greater improvements than placebo in the I-QOL total and subscale scores at all follow-up visits from week 2 through week 24 ( p<0.05 ) . OnabotulinumtoxinA doses≥100 U produced significantly greater improvements than placebo in the KHQ symptom score at a majority of follow-up visits . HRQOL instruments demonstrated low to moderate correlations ( Spearman correlation range : 0.01 - 0.51 ) with the symptoms of UUI recorded using daily diary data , with I-QOL demonstrating the highest correlations . A study limitation was that certain quality -of-life measures were exploratory and not vali date d. CONCLUSIONS A single onabotulinumtoxinA treatment with doses≥100 U result ed in statistically significant and clinical ly meaningful improvement in HRQOL by week 2 compared with placebo , and this improvement was sustained for ≤36 wk in patients with idiopathic OAB and UUI who were inadequately managed by oral antimuscarinics . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00168454 OBJECTIVE To compare two new generation antimuscarinics at their recommended doses for treatment of overactive bladder syndrome ( OAB ) . METHODS A prospect i ve , double blind , double-dummy , two-arm , parallel-group , 12-week study was conducted to compare the efficacy and safety of solifenacin 5 or 10 mg and tolterodine extended release ( ER ) 4 mg once daily in OAB patients . After 4 weeks of treatment patients had the option to request a dose increase but were dummied throughout as approved product labelling only allowed an increase for those on solifenacin . RESULTS Solifenacin , with a flexible dosing regimen , showed greater efficacy to tolterodine in decreasing urgency episodes , incontinence , urge incontinence and pad usage and increasing the volume voided per micturition . More solifenacin treated patients became continent and reported improvements in perception of bladder condition assessment s. The majority of side effects were mild to moderate in nature , and discontinuations were comparable and low in both groups . CONCLUSIONS Solifenacin , with a flexible dosing regimen , was found to be superior to tolterodine ER with respect to the majority of the efficacy variables OBJECTIVES In this double-blind , placebo-controlled trial , we assessed the efficacy and tolerability of solifenacin treatment for overactive bladder ( OAB ) with a focus on urgency-related endpoints . Changes in number of urgency episodes were evaluated as the primary endpoint ; secondary endpoints included changes in conventional diary-based OAB symptoms . We also measured warning time ( defined as the time from first sensation of urgency to voiding ) . METHODS We r and omized patients ( n = 739 ) to once-daily solifenacin or placebo for 12 weeks . Solifenacin 5 mg or matching placebo was administered for 4 weeks ; dose could be maintained or adjusted at weeks 4 and 8 . Participants completed 3-day micturition diaries at multiple study visits ; warning time was recorded at baseline and week 12 . RESULTS At study end , the mean number of urgency episodes per 24 hours decreased by 3.91 ( from 6.15 to 2.24 ) with solifenacin and by 2.73 ( from 6.03 to 3.30 ) with placebo ( P < .0001 between groups ) . Other diary-recorded symptoms ( incontinence and micturition frequency ) were also significantly more reduced with solifenacin compared with placebo .  Median warning time increased 31.5 seconds ( baseline , 67.8 seconds ) with solifenacin , significantly longer ( P = .008 ) than the median increase of 12.0 seconds ( baseline , 65.0 seconds ) observed with placebo . CONCLUSIONS Solifenacin treatment significantly reduced episodes of urgency and other key symptoms of OAB . Solifenacin is the first antimuscarinic to demonstrate significant warning time improvement at approved dosing , as shown in a large OAB study population . This is the largest OAB clinical trial yet conducted to evaluate warning time and diary variables in the same study population OBJECTIVE To investigate associations between diet and non-dietary lifestyle factors and the onset of  overactive bladder ( OAB ) in men . SUBJECTS R and om sample of community-dwelling men aged 40 years plus . DESIGN AND METHODS Baseline data on  urinary symptoms and  diet  were collected from 5454 men using a postal question naire and a food-frequency question naire . Follow-up data on urinary symptoms were collected from 4887 men in a postal survey one year later .  Logistic regression analysis  was used to investigate diet and lifestyle factors associated with onset of OAB in the men without OAB at baseline . RESULTS There was a highly significant negative association between beer intake at baseline and subsequent OAB onset ( P=0.001 ) , with reduced risk at all levels of intake compared with those who seldom/never drank beer . Adjustment for total alcohol intake ( g ethanol day(-1 ) ) reduced the significance of the association ( P=0.02 ) . None of the food groups studied was associated with OAB onset , with the possible exception of potatoes ( P=0.05 ) , which showed an increased risk of onset at the highest level of consumption . Physical activity , smoking and obesity were not significantly associated . CONCLUSIONS While most diet and lifestyle factors were not associated with OAB onset , the evidence from this prospect i ve longitudinal study suggests that beer may have a protective role in the development of OAB . This could be due to a non-alcoholic ingredient as well as the alcohol content OBJECTIVES To assess the efficacy and safety of solifenacin add-on therapy to tamsulosin in lower urinary tract symptoms ( LUTS ) men with residual overactive bladder ( OAB ) symptoms despite tamsulosin monotherapy . METHODS In this r and omized , multicenter , double-blind study , male LUTS patients aged≥50 years with urgency episodes/24 hours≥2 and micturitions/24 hours≥8 were r and omized to 3 groups : 12-weeks tamsulosin plus placebo ( TAM+PBO ) , tamsulosin plus solifenacin 2.5 mg ( TAM+SOL ) , and tamsulosin plus solifenacin 5 mg ( TAM+SOL ) . Changes from baseline to end of treatment in the number of urgency episodes/24 hours ( primary endpoint ) , micturitions , nocturia , urgency incontinence episodes , International Prostate Symptom Scores ( IPSS ) , and Overactive Bladder Symptom Score ( OABSS ) were compared between the TAM+SOL groups and TAM+PBO . Safety was assessed on adverse events , postvoid residual volume , and maximal urinary flow rate ( Qmax . ) . RESULTS Six-hundred thirty-eight men were r and omized . Urgency was reduced by 2.2 and 2.4 episodes in the TAM+SOL 2.5 and 5 mg groups , respectively . The TAM+SOL 5 mg group showed significant improvement compared with TAM+PBO ( -2.4 vs -1.9 , P=.049 ) . The number of micturitions in both TAM+SOL groups were significantly reduced compared with TAM+PBO ( both P<.001 ) . IPSS storage symptom score and OABSS significantly improved in both TAM+SOL groups compared with TAM+PBO . Changes in IPSS voiding symptom score and Qmax . were similar in all groups . Four patients ( 1.9 % ) in the TAM+SOL 5 mg group had urinary retention , but all recovered after catheterization . CONCLUSIONS In male LUTS patients with residual OAB symptoms  despite tamsulosin monotherapy , TAM+SOL showed efficacy on urgency , which represents OAB symptoms and was well tolerated BACKGROUND Combining the β3-adrenoceptor agonist mirabegron and the antimuscarinic ( AM ) agent solifenacin may improve efficacy in the treatment of overactive bladder ( OAB ) while reducing the AM side effects . OBJECTIVE The primary objective was to evaluate the efficacy of combinations of solifenacin/mirabegron compared with solifenacin 5 mg monotherapy . The secondary objective was to explore the dose-response relationship and the safety/tolerability compared with placebo and monotherapy . DESIGN , SETTING , AND PARTICIPANTS A phase 2 , factorial design , r and omised , double-blind , parallel-group , placebo- and monotherapy-controlled trial , conducted at 141 sites in 20 European countries . Male and female patients were aged ≥18 yr with symptoms of OAB for ≥3 mo . INTERVENTION A total of 1306 patients ( 66.4 % female ) were r and omised to 12 wk of treatment in 1 of 12 groups : 6 combination groups ( solifenacin 2.5 , 5 , or 10 mg plus mirabegron 25 or 50 mg ) , 5 monotherapy groups ( solifenacin 2.5 , 5 , or 10 mg , or mirabegron 25 or 50 mg ) , or placebo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Change from baseline to end of treatment in mean volume voided per micturition ( MVV ) ( primary end point ) and mean numbers of micturitions per 24 h , incontinence episodes per 24 h , and urgency episodes per 24 h were analysed using an analysis of covariance model . Safety assessment s included treatment-emergent adverse events ( TEAEs ) , blood pressure , pulse rate , postvoid residual ( PVR ) volume , and laboratory and electrocardiography ( ECG ) parameters . RESULTS AND LIMITATIONS Compared with solifenacin 5 mg monotherapy , all combinations with solifenacin 5 or 10 mg significantly improved MVV , with adjusted differences ranging from 18.0 ml ( 95 % confidence interval [ CI ] , 5.4 - 30.0 ) to 26.3 ml ( 95 % CI , 12.0 - 41.0 ) . Three combination groups significantly reduced micturition frequency  compared with solifenacin 5 mg , ranging from -0.80 ( 95 % CI , -1.39 to -0.22 ) to -0.98 ( 95 % CI , -1.68 to -0.27 ) . Five of six combinations significantly reduced urgency episodes compared with solifenacin 5 mg , ranging from -0.98 ( 95 % CI , -1.78 , to -0.18 ) to -1.37 ( 95 % CI , -2.03 to -0.70 ) . No dose-related trends in TEAEs , blood pressure , pulse rate , PVR volume , or laboratory or ECG parameters were observed between combination and monotherapy groups , although the incidence of constipation was slightly increased with combination therapy . CONCLUSIONS Combination therapy with solifenacin/mirabegron significantly improved MVV , micturition frequency , and urgency compared with solifenacin 5 mg monotherapy . All combinations were well tolerated , with no important additional safety findings compared with monotherapy or placebo . PATIENT SUMMARY To improve treatment of overactive bladder ( OAB ) , mirabegron/solifenacin in combination was compared with each drug alone and placebo . Combination therapy improved OAB symptoms and had similar safety and acceptability . TRIAL REGISTRATION Clinical trials.gov : NCT01340027
Data from 12-week , r and omised , double-blind , placebo-controlled trials of tolterodine extended release ( ER ) , oxybutynin and solifenacin show that combined antimuscarinic+α-blocker treatment is generally more effective than monotherapy or placebo in men with OAB symptoms .
The efficacy and safety  of tolterodine ER+α-blocker treatment was not affected by prostate size or prostate-specific antigen ( PSA ) level .
In men meeting entry criteria for OAB and benign prostatic obstruction trials  , tolterodine ER alone was effective selectively in men with prostate size or PSA level below study medians .
Post hoc analyses from double-blind , placebo-controlled trials and prospect i ve studies of fesoterodine , oxybutynin , propiverine , solifenacin and tolterodine also suggest that antimuscarinics are generally safe and efficacious in men .
A retrospective data base study found that risk of AUR in men was the highest in the first month of treatment and decreased considerably thereafter .
Antimuscarinics , alone or with an α-blocker , appear to be efficacious and safe in many men with predominant OAB symptoms or persistent OAB symptoms despite α-blocker or 5-α-reductase inhibitor treatment .
Despite potential benefits , primary care clinicians may avoid using antimuscarinics in men with overactive bladder ( OAB ) symptoms because of safety concerns .