Efficacy and safety of tolterodine extended-release in men with overactive bladder symptoms treated with an α-blocker: effect of baseline prostate-specific antigen concentration.

OBJECTIVE: To determine whether the efficacy and safety of a combination of tolterodine extended-release (ER) plus α-blocker treatment varies with high or low levels of serum prostate-specific antigen (PSA) in men who have persistent overactive bladder (OAB) symptoms after any α-blocker monotherapy. PATIENTS AND METHODS: Men aged ≥ 40 years were eligible if they reported ≥ 8 micturitions/24 h, including ≥ 1 urgency episode/24 h with or without urgency urinary incontinence (UUI), and at least some moderate bladder-related problems at baseline despite receiving treatment with an α-blocker for ≥ 1 month. Exclusion criteria included a postvoid residual urine volume (PVR) of ≥ 200 mL and history of acute urinary retention requiring catheterization. Subjects were randomly assigned to tolterodine-ER 4 mg or placebo for 12 weeks; all subjects continued their α-blocker treatment throughout the study. Subjects completed 5-day bladder diaries at baseline and week 12, in which they recorded all micturitions and rated the sensation associated with each micturition using the 5-point Urinary Sensation Scale (USS). For this post hoc analysis, efficacy, safety, and tolerability data were stratified by the study median PSA concentration at baseline (1.41 ng/mL). RESULTS: In the tolterodine-ER +α-blocker and placebo +α-blocker groups, 160 and 159 men, respectively, had PSA levels of <1.41 ng/mL, and 166 and 160 men, respectively, had PSA levels of ≥ 1.41 ng/mL. Men with higher PSA levels were slightly older and had higher PVR at baseline compared with men with lower PSA levels. At week 12, improvements in daytime micturitions, 24-h urgency episodes, and daytime urgency episodes were significantly greater with tolterodine-ER +α-blocker vs placebo +α-blocker both in men with PSA levels of ≥ 1.41 ng/mL and those with PSA levels of < 1.41 ng/mL (P < 0.05). Among men with PSA levels of < 1.41 ng/mL, improvements in 24-h micturitions and frequency-urgency sum (sum of USS ratings for all micturitions) were also significantly greater with tolterodine-ER +α-blocker vs placebo +α-blocker (P < 0.05). There were no significant treatment differences in change in UUI episodes in either PSA group (although only 19% of subjects reported UUI at baseline), nor in nocturnal micturitions or nocturnal urgency episodes. Among men with PSA levels of ≥ 1.41 ng/mL, there was a statistically significant increase in PVR (P = 0.036) and decrease in maximum urinary flow rate (Q(max); P = 0.038) with tolterodine-ER +α-blocker vs placebo +α-blocker; these changes were not considered clinically meaningful. There were no treatment differences for changes in PVR or Q(max) among men with PSA levels of < 1.41 ng/mL. One subject receiving tolterodine-ER +α-blocker (PSA concentration of ≥ 1.41 ng/mL) and two subjects receiving placebo +α-blocker (one each in the PSA concentration subgroups of ≥ 1.41 ng/mL and < 1.41 ng/mL) had acute urinary retention requiring catheterization. CONCLUSION: In a 12-week study, the addition of tolterodine-ER to α-blocker therapy improved key OAB symptoms and appeared to be well tolerated compared with placebo +α-blocker in men with persistent OAB symptoms, regardless of subjects' prostate size as judged by serum PSA concentration.

Fesoterodine in patients with overactive bladder syndrome: can the severity of baseline urgency urinary incontinence predict dosing requirement?

OBJECTIVES: To determine whether baseline urgency urinary incontinence (UUI) episodes predict the need for increased doses of fesoterodine in patients with overactive bladder (OAB), as clinicians would benefit from data that help to predict which patients require higher doses of antimuscarinics to manage UUI episodes. PATIENTS AND METHODS: In this pooled analysis of data from two double-blind, placebo-controlled trials, patients were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks and stratified into tertiles (>0-<2, 2-<4, or > or =4) according to the number of UUI episodes/24 h as recorded in 3-day bladder diaries at baseline. The change in mean UUI episodes/24 h from baseline to end of study was assessed using analysis of covariance. RESULTS: In a post hoc analysis of data from two clinical trials, there were significant reductions from baseline in UUI episodes for fesoterodine 4 and 8 mg vs placebo in patients (n) with >0-<2 (422), 2-<4 (424) and > or =4 (481) UUI episodes at baseline (all P < 0.01). In patients with 2-<4 and > or =4 UUI episodes at baseline, fesoterodine 8 mg gave significantly greater mean reductions (-1.92 and -4.17, respectively) vs fesoterodine 4 mg (-1.43 and -3.31) (P < 0.05). The most common adverse events were dry mouth (placebo, 8%; fesoterodine 4 mg, 19%; and 8 mg, 35%) and constipation (placebo, 2%; fesoterodine 4 mg, 5%; and 8 mg, 6%). CONCLUSION: Fesoterodine 4 and 8 mg significantly reduced UUI episodes vs placebo; this effect appeared to be greater with fesoterodine 8 mg in patients with > or =2 UUI episodes/24 h at baseline. Fesoterodine was well tolerated, although higher doses increased the incidence of adverse events. These findings might aid the clinical identification of patients with OAB who would most benefit from increasing the dose of fesoterodine from 4 to 8 mg.

Correlations among improvements in urgency urinary incontinence, health-related quality of life, and perception of bladder-related problems in incontinent subjects with overactive bladder treated with tolterodine or placebo.

BACKGROUND: Previous studies demonstrate that tolterodine extended release (ER) significantly improves urgency urinary incontinence (UUI) episodes. Instruments that measure patient-reported outcomes (PROs) provide additional information that is valuable for assessing whether clinical improvements are meaningful to the patient. This study determined the correlation of changes in bladder diary variables and other PROs in subjects with overactive bladder (OAB). METHODS: Subjects with OAB, urinary frequency, and UUI were treated with 4 mg once-daily tolterodine ER or placebo for 12 weeks. Subjects completed 7-day bladder diaries, the Patient Perception of Bladder Condition (PPBC), and the King's Health Questionnaire (KHQ) at baseline and week 12. Only subjects who reported at least some minor bladder-related problems at baseline (PPBC score > or = 3) were included in this analysis. RESULTS: Reductions in UUI episodes per week were significantly greater in the tolterodine ER group (n = 500) compared with the placebo group (n = 487) at week 12 (-71% vs -33%, P < 0.0001). A significantly greater percentage of subjects in the tolterodine ER group reported improvement on the PPBC versus placebo (58% vs 45%, P < 0.0001), and 7 of 10 KHQ domains were significantly improved versus placebo (all P < 0.05). Significant correlations were found for median percentage changes in UUI episodes with changes in PPBC scores (r = 0.35,P < 0.0001) and the 7 improved KHQ domains (r = 0.16-0.32, P < or = 0.0011). Changes in PPBC scores and all KHQ domains were significantly correlated (r = 0.13-0.38, P < or = 0.009) in the tolterodine ER group. Correlations among endpoints in the placebo group were similar to those observed in the tolterodine ER group. CONCLUSION: Improvement in UUI episodes after 12 weeks of treatment with tolterodine ER or placebo was correlated with improvements in patients' perception of their bladder-related problems and health-related quality of life. Correlations were moderate in magnitude but statistically significant, suggesting that PROs are important and relevant measures for evaluating OAB treatment.

Impact of fesoterodine on quality of life: pooled data from two randomized trials.

OBJECTIVE: To evaluate the effect of fesoterodine on health-related quality of life (HRQoL) in patients with overactive bladder (OAB) syndrome. PATIENTS AND METHODS: Pooled data from two randomized placebo-controlled phase III studies were analysed. Eligible patients with frequency and urgency or urgency urinary incontinence were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks; one trial also included tolterodine extended release (tolterodine-ER) 4 mg. HRQoL was assessed using the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), a six-point Likert scale measuring the severity of bladder-related problems, and treatment response. RESULTS: By the end of treatment, all active-treatment groups had significantly improved HRQoL compared with those on placebo, as shown by an improvement in the KHQ and ICIQ-SF scores, treatment response rate, and a major improvement in self-reported bladder-related problems. The fesoterodine 8-mg group had statistically significant improvements over placebo in eight of nine KHQ domains. Fesoterodine 4 mg and tolterodine-ER produced statistically significant improvements in seven of nine KHQ domains. Fesoterodine 8 mg gave better results than 4 mg in two domains; Emotions and Symptom Severity (P < 0.05). A major improvement (>or=2 points) in bladder-related problems was reported by 33% of patients on fesoterodine 4 mg, 38% on fesoterodine 8 mg, and 34% on tolterodine-ER, vs 21% on placebo (P < 0.001). CONCLUSIONS: Fesoterodine significantly improved HRQoL in patients with OAB. Both fesoterodine 4 and 8 mg produced significant improvements on most KHQ domains, the ICIQ-SF, treatment response rate, and a Likert scale measuring bladder-related problems.

Comparison of fesoterodine and tolterodine in patients with overactive bladder.

OBJECTIVE: To compare, in a post hoc analysis of a phase III trial, the maximum recommended doses of fesoterodine (8 mg) and tolterodine (4 mg) for improving overactive bladder (OAB) symptoms and health-related quality of life (HRQoL), as fesoterodine effectively reduces OAB symptoms vs placebo. PATIENTS AND METHODS: Eligible patients with frequency (> or =eight voids/24 h) and either urgency (> or =six episodes over 3 days) or urgency urinary incontinence (UUI; > or =three episodes over 3 days) were randomized to placebo, fesoterodine 4 or 8 mg, or tolterodine extended-release (ER) 4 mg for 12 weeks; fesoterodine 4 mg data were published elsewhere. Patients completed a 3-day bladder diary in which they recorded the time of each void, voided volume (VV), and the severity of urgency. A post hoc inferential analysis was conducted on the primary endpoint (voids/24 h), the two co-primary endpoints (UUI episodes/24 h and treatment response), several secondary endpoints (severe urgency plus UUI per 24 h, mean VV (MVV)/void, and continent days/week), HRQoL, using the King's Health Questionnaire (KHQ) and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and self-reported bladder-related problems. A subanalysis also assessed all endpoints for patients who were incontinent at baseline. Tolerability and safety were assessed by evaluating adverse events, residual urine volume, laboratory variables and treatment withdrawals. RESULTS: By week 12, patients with OAB in both active-treatment groups showed significant improvements in most bladder diary variables and treatment response rates compared with placebo. Fesoterodine 8 mg was statistically significantly better than tolterodine ER 4 mg for improving UUI episodes, severe urgency plus UUI, mean VV, and number of continent days/week. In addition, the fesoterodine and tolterodine ER groups showed significantly greater improvements in HRQoL than the placebo group, with positive changes in most domains of the KHQ and an improvement in ICIQ-SF score. The fesoterodine 8-mg group had statistically significant improvements over placebo in eight of nine KHQ domains. A major improvement in the severity of bladder-related problems was reported by 39% of the fesoterodine 8 mg and 34% of the tolterodine ER groups vs 25% of those on placebo (P < or = 0.01). Results for the subgroup of incontinent patients at baseline were similar to the overall results. Adverse events reported most commonly with active treatment included dry mouth, constipation, dry eye, dry throat, and nausea. CONCLUSIONS: Both fesoterodine and tolterodine ER significantly improved OAB symptoms and HRQoL, with statistically significant advantages for fesoterodine 8 mg compared with tolterodine ER on several important endpoints.

Impact of chest pain on cost of migraine treatment with almotriptan and sumatriptan.

Chest-related symptoms occur with all triptans; up to 41% of patients with migraine who receive sumatriptan experience chest symptoms, and 10% of patients discontinue treatment. Thus, the cost of chest pain-related care was estimated in migraineurs receiving almotriptan 12.5 mg versus sumatriptan 50 mg. A population-based, retrospective cohort study used data to quantify the incidence and costs of chest pain-related diagnoses and procedures. An economic model was constructed to estimate annual cost savings per 1000 patients receiving almotriptan versus sumatriptan based on the reported rates of chest pain. Annual direct medical cost avoided was calculated for a hypothetical health plan covering 1 million lives. Among a cohort of 1390 patients, the incidence of chest pain-related diagnoses increased significantly by 43.6% with sumatriptan (P=.003). Aggregate costs for chest pain-related diagnoses and procedures increased from $22,713 to $30,234. Payments for inpatient hospital services, costs for primary care visits, and costs for outpatient hospital visits increased by over 100%, 53.1%, and 14.4%, respectively. The model predicted $11,215 in direct medical cost savings annually per 1000 patients treated with almotriptan versus sumatriptan. Annual direct medical costs avoided totaled $194,358, and when applied to recent estimates of 86 million lives currently covered by almotriptan treatment, translates into an annual cost savings of just under $17 million for chest pain and associated care. Thus, using almotriptan in place of sumatriptan will likely reduce the cost of chest pain-related care.

Cost savings in migraine associated with less chest pain on new triptan therapy.

OBJECTIVES: This article constructs an economic model to estimate cost of chest-pain-related care in migraine patients receiving almotriptan 12.5 mg compared with those receiving sumatriptan 50 mg. STUDY DESIGN: This population-based, retrospective cohort study used data from the MEDSTAT Marketscan database (Ann Arbor, Michigan) to quantify incidence and costs of chest-pain-related diagnoses and procedures. After a 6-month exclusion period, the study used a pre-post design, with baseline and treatment periods defined, respectively, as 5 months before and after receiving sumatriptan therapy. An economic model was constructed to estimate annual cost savings per 1,000 patients receiving almotriptan instead of sumatriptan as a function of differing rates of chest pain. Annual direct medical cost avoided was calculated for a hypothetical health plan covering 1 million lives. RESULTS: Among a cohort of 1,390 patients, the incidence of chest-pain-related diagnoses increased significantly (43.6%) with sumatriptan, from 110 during the baseline period to 158 during the treatment period (P= .003). Aggregate costs for chest-pain-related diagnoses and procedures increased 33.1%, from $22,713 to $30,234. Payments for inpatient hospital services rose 10-fold; costs for primary care visits and outpatient hospital visits rose 53.1% and 14.4%, respectively. Payments for angiography increased from $0 to $462, and costs for chest radiographs and electrocardiograms increased 58.7% and 31.2%, respectively. Sumatriptan treatment was associated with a 3-fold increase in payments for services for painful respiration and other chest pain. The model predicted $11,215 in direct medical cost savings annually per 1000 patients treated with almotriptan instead of sumatriptan. Annual direct medical costs avoided for the health plan totaled $195,913. CONCLUSION: Using almotriptan instead of sumatriptan will likely reduce the cost of chest-pain-related care for patients with migraine headaches.

Defining response and non-response to treatment in patients with overactive bladder: a systematic review.

OBJECTIVE: There is currently a lack of formal guidance for assessing treatment response and non-response in patients with overactive bladder (OAB). Such guidance would be useful for both clinical practice and the design of clinical trials. Our purpose was to review and assess definitions of treatment response and non-response used in patients with OAB. METHODS: We conducted a systematic review of articles published between January 1, 2005 and August 8, 2013 using PubMed. Search terms included (overactive bladder) AND ('treatment response' OR responder OR success OR satisfied OR goal OR refractory OR nonresponder OR fail OR persistent OR dissatisfied). Limits were 'humans' and 'English'. Studies conducted in subjects with neurogenic detrusor overactivity, conditions other than OAB, or OAB symptoms following lower urinary tract/pelvic surgery were excluded; case reports and letters were also excluded. RESULTS: The literature search returned 423 articles, of which 75 met the inclusion criteria and defined a specific threshold by which treatment response or non-response was determined for patients receiving behavioral therapy and/or treatment with an antimuscarinic, ß3-agonist, botulinum toxin, or neural stimulation. One published abstract from congress proceedings and three additional articles that were not identified by the search were included; thus, a total of 79 records were included. A wide variety of symptom-based definitions and patient-reported outcomes (PROs) were used. Symptom-based definitions frequently used a threshold of 50-100% improvement in general or specific symptoms; urgency urinary incontinence (UUI) was often used in studies with incontinent patients. Definitions based on PROs frequently used measures of satisfaction, general improvement, or goal achievement. Studies of patients with refractory OAB often referred to a failure to respond to ≥1 other therapy, or to poor efficacy or unacceptable tolerability, without further specification. Limitations of this review are that only English language articles were included and that only the PubMed database was used for the literature search. CONCLUSIONS: There is considerable heterogeneity in the definitions of treatment response and non-response in trials of patients with OAB; some standardization would be beneficial. However, there is also heterogeneity among patients of what constitutes treatment success or failure, and conceptualizations of treatment response and non-response in both clinical trials and clinical practice must take patient characteristics into account. For patients with UUI, it is recommended that the criteria for treatment response include this symptom, as measured by change in the absolute number of UUI episodes or achievement of continence, given its impact on patients' lives and associated bother. PROs provide important information that confirm symptom-based measures by demonstrating that observed changes in symptoms are meaningful to the patient. In clinical practice, measures of treatment satisfaction and goal achievement can be highly useful.

Efficacy and tolerability of fesoterodine in men with overactive bladder: a pooled analysis of 2 phase III studies.

OBJECTIVES: To assess the efficacy, safety, and tolerability of fesoterodine 4 and 8 mg in men with overactive bladder. METHODS: This was a subanalysis of pooled data from 358 men enrolled in 2 double-blind, placebo-controlled phase III trials. Subjects with frequency and urgency or urgency urinary incontinence (UUI) were randomized to fesoterodine 4 mg, fesoterodine 8 mg, or placebo for 12 weeks. Efficacy endpoints included bladder diary variables and subject-reported treatment response. RESULTS: By week 12, men treated with fesoterodine 4 or 8 mg had significantly greater median percentage improvements in micturition frequency, urgency episodes, and UUI episodes versus placebo and significantly greater percentages reported a treatment response versus placebo. Significant increases in mean voided volume (MVV) per micturition versus placebo occurred with fesoterodine 8 mg only. At week 12, fesoterodine 8 mg was significantly more efficacious than fesoterodine 4 mg in improving UUI episodes and MVV per micturition. The most commonly reported adverse events with fesoterodine 4 and 8 mg were dry mouth (12.5% and 37.7% vs 5.6% with placebo) and constipation (2.5% and 8.8% vs 0.8% with placebo). Symptoms suggestive of urinary retention were reported in 0.8%, 0.8%, and 5.3% of men in the placebo, fesoterodine 4 mg, and fesoterodine 8 mg groups, respectively; only 1 subject, in the fesoterodine 8 mg group, was catheterized. CONCLUSIONS: Fesoterodine 4 and 8 mg are generally safe, efficacious, and well tolerated for the treatment of overactive bladder symptoms in men. The 8 mg dose provides additional benefit and allows for treatment individualization.

Efficacy and tolerability of fesoterodine in older and younger subjects with overactive bladder.

OBJECTIVES: To assess the effect of age on fesoterodine efficacy and tolerability in subjects with an overactive bladder. METHODS: The data from 2 randomized, 12-week studies of 1681 subjects treated with fesoterodine 4 or 8 mg or placebo were pooled and stratified by age. The subjects completed 3-day bladder diaries at baseline and weeks 2 and 12, the King's Health Questionnaire at baseline and week 12, and the Treatment Benefit Scale at week 12. RESULTS: Of the subjects aged <65 years, fesoterodine 4 and 8 mg was associated with statistically significant improvements in the diary variables at week 12 versus placebo. Greater improvement in urgency urinary incontinence was seen with fesoterodine 8 mg versus 4 mg. For those aged ≥65 to <75 years, fesoterodine 4 and 8 mg significantly improved all diary variables, except for the mean voided volume and micturition frequency, respectively, [corrected] versus placebo. In subjects aged ≥75 years, fesoterodine 8 mg significantly improved all diary variables, except for mean voided volume, versus placebo. No significant improvements were observed with fesoterodine 4 mg versus placebo. Fesoterodine significantly improved several King's Health Questionnaire domains versus placebo in all age groups. Fesoterodine 4 mg did not significantly improve any domains in subjects aged ≥75 years. In all age groups, the treatment response rates were significantly greater with both fesoterodine doses versus placebo. Dry mouth and constipation occurred more frequently in subjects aged ≥75 years receiving fesoterodine 8 mg than in those receiving fesoterodine 4 mg or placebo, although the discontinuation rates because of dry mouth and constipation were not increased. CONCLUSIONS: Fesoterodine 4 and 8 mg effectively treated overactive bladder symptoms in subjects aged <75 years. Fesoterodine 8 mg was effective in subjects aged ≥75 years.

Tolterodine extended release with or without tamsulosin in men with lower urinary tract symptoms including overactive bladder symptoms: effects of prostate size.

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 randomized 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 clinically or statistically significant changes in Q(max) or PVR; incidence of acute urinary retention (AUR) was low in all groups (

Effects of tolterodine extended release on patient perception of bladder condition and overactive bladder symptoms*.

OBJECTIVE: To evaluate the efficacy of tolterodine extended release (ER) versus placebo at 1 and 12 weeks using questionnaires and diary measures. RESEARCH DESIGN AND METHODS: Subjects with overactive bladder (OAB) were randomized to receive tolterodine ER (4 mg) or placebo for 12 weeks. This double-blind study is registered with ClinicalTrials.gov (identifier: NCT00143377). MAIN OUTCOME MEASURES: Subjects completed the Patient Perception of Bladder Condition (PPBC) and 3-day bladder diaries at baseline and weeks 1 and 12, and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. PPBC score changes were analyzed using 2-category (improvement, no improvement), 3-category (improvement, no change, deterioration), and 4-category (>or=2-point improvement, 1-point improvement, no change, deterioration) stratifications. Categorical change in PPBC scores from baseline to week 12 was the primary endpoint. RESULTS: A total of 617 subjects were randomized (tolterodine ER, n = 410; placebo, n = 207). At week 1, a significantly higher percentage of subjects receiving tolterodine ER reported improvement on the PPBC compared with placebo (p < 0.05). Subjects receiving tolterodine ER also had a significantly greater reduction in all OAB symptoms versus placebo (all p < 0.05). At week 12, a higher percentage of tolterodine ER subjects reported PPBC improvement versus placebo subjects. This was significant in the 3- and 4-category analyses (both p < 0.05) but not in the 2-category analysis (the prespecified method of analysis; p = 0.098). Compared with the placebo group, the tolterodine ER group reported significantly greater week 12 improvements in all bladder diary variables (all p < 0.01) as well as in OAB-q Symptom Bother, total Health-Related Quality of Life, Coping, and Concern scores (all p

Effects of serum PSA on efficacy of tolterodine extended release with or without tamsulosin in men with LUTS, including OAB.

OBJECTIVES: To evaluate the efficacy of tolterodine extended release (ER), tamsulosin, and tolterodine ER plus tamsulosin in men with symptoms of overactive bladder and benign prostatic hyperplasia stratified by prostate-specific antigen (PSA) level. METHODS: We performed a post hoc analysis of data from men >or=40 years old with frequency and urgency (with or without urge urinary incontinence), postvoid residual urine volume <200 mL, maximal urinary flow rate >5 mL/s, International Prostate Symptom Score (IPSS) of >or=12, and quality-of-life score of >or=3. They had been randomized to placebo, tolterodine ER (4 mg), tamsulosin (0.4 mg), or tolterodine ER plus tamsulosin for 12 weeks. The men were stratified by the median baseline PSA level (>or=1.3 vs <1.3 ng/mL). Assessments included changes in bladder diary variables and IPSSs. The men rated the urgency level of each micturition, and the frequency-urgency sum was defined as the total of these ratings. RESULTS: The PSA level correlated significantly with prostate size. Men with a PSA level of >or=1.3 ng/mL receiving tolterodine ER plus tamsulosin showed significantly greater improvements in 24-hour frequency, daytime frequency, the frequency-urgency sum, total IPSS, and IPSS storage score compared with those receiving placebo. Tamsulosin significantly improved the IPSS voiding scores, but tolterodine ER was ineffective. In men with a PSA level <1.3 ng/mL, tolterodine ER alone and tolterodine ER plus tamsulosin significantly improved the 24-hour frequency, daytime frequency, frequency-urgency sum, and IPSS storage scores compared with those receiving placebo; tamsulosin alone was ineffective. No significant changes were found in the postvoid residual urine volume or maximal urinary flow rate in any group, and the acute urinary retention rates were low. CONCLUSIONS: The results of our study have shown that tolterodine ER was efficacious in men with lower urinary tract symptoms, including overactive bladder, who had lower PSA levels (<1.3 ng/mL).

Tolterodine extended release is efficacious in continent and incontinent subjects with overactive bladder.

OBJECTIVES: To assess efficacy and tolerability of tolterodine extended release (ER) in continent and incontinent subjects with overactive bladder (OAB). METHODS: This was a post hoc analysis of data from a 12-week, double-blind, placebo-controlled trial of tolterodine ER (4 mg once daily). Subjects completed 7-day bladder diaries at baseline and week 12; those with one or more incontinence episode(s) in their diaries at baseline were considered incontinent. Subjects rated urgency associated with each micturition on a scale from 1 to 5, and micturitions were categorized post hoc by urgency rating as non-OAB (1-2), OAB (3-5), or severe OAB (4-5). RESULTS: At baseline, 40% of subjects were incontinent. Tolterodine ER (n = 429) reduced total, OAB, and severe OAB micturitions compared with placebo (n = 421) in continent and incontinent subjects. There was no difference between continent and incontinent subjects in terms of the magnitude of improvement with tolterodine ER relative to placebo for total, OAB, and severe OAB micturitions. Reductions in mean urgency and frequency-urgency sum ratings were significantly greater in the tolterodine ER group. Among incontinent subjects, tolterodine ER significantly reduced urgency urinary incontinence episodes and significantly increased the percentage of subjects achieving continence relative to placebo. Adverse event rates were low in both continent and incontinent subjects. CONCLUSIONS: Tolterodine ER reduced micturitions associated with urgency (OAB or severe OAB) in both continent and incontinent subjects. Tolterodine ER also reduced urgency urinary incontinence episodes in incontinent subjects. These data show that tolterodine ER is effective and well tolerated in both continent and incontinent subjects with OAB.

Achieving continence with antimuscarinic therapy for overactive bladder: effects of baseline incontinence severity and bladder diary duration.

OBJECTIVE: To examine the continence ('dryness') rate as an outcome measure of the efficacy of antimuscarinic treatment, and to explore how changes in bladder diary duration, baseline severity of urinary incontinence (UI), and study population characteristics affected this outcome. PATIENTS AND METHODS: Urgency UI is a symptom of overactive bladder (OAB) and antimuscarinic agents are a first-line treatment for OAB symptoms; several studies have used dryness rate as an efficacy endpoint, calculated as the percentage of patients who record no UI episodes in a diary period. We performed a post hoc analysis of data from a 12-week, multicentre, randomized, double-blind, placebo-controlled trial of tolterodine extended-release (ER) in patients with symptoms of urinary frequency (> or =8 voids/24 h) and urgency UI (> or =5 episodes/week). Patients with stress UI were excluded. Diary entries from the 3-, 5-, and 7-day periods immediately preceding the baseline and the week 12 visit were used to assess the relationships between the percentage of patients reporting total dryness at week 12, diary duration (3, 5, or 7 days), baseline number of weekly UI episodes (1-6, 7-13, 14-20, > or = 21), and population analysed (intent-to-treat, ITT, or per protocol, PP). The mean changes in weekly UI episodes from baseline to week 12 are also reported by diary duration and baseline frequency of UI for patients treated with tolterodine-ER. RESULTS: The total dryness rates decreased with increasing diary duration and greater frequency of UI at baseline. Analysis of the ITT population also showed lower dryness rates than the PP population. However, the mean reductions in weekly UI episodes for the ITT and PP populations were consistent across diary duration for each level of baseline UI frequency. CONCLUSION: 'Dryness' varies with diary duration, baseline frequency of UI, and the population analysed. Comparisons of dryness rates between studies might lead to erroneous conclusions when these factors are not considered.

Age related pathogenesis of nocturia in patients with overactive bladder.

PURPOSE: Nocturia is caused by increased nocturnal urine output (nocturnal polyuria) and/or diminished nocturnal bladder capacity. We retrospectively evaluated the causes of nocturia in patients with overactive bladder and nocturia. MATERIALS AND METHODS: A total of 850 patients (18 years or older) with symptoms of overactive bladder (8 or more micturitions per 24 hours and urgency or urgency urinary incontinence) and nocturia (mean of 2.5 or more episodes per night) were enrolled in a 12-week study of tolterodine ER (4 mg QD) vs placebo. Of this total 845 patients (417 men and 428 women) completed 7-day bladder diaries. Patients were stratified post hoc by sex and age groups (less than 50, 50 to 70, more than 70 years). Indices of nocturnal urine production (nocturia index, nocturnal polyuria index and nocturnal bladder capacity index) were compared using ANOVA (alpha level 0.05). Higher nocturia index and nocturnal polyuria index values suggest that nocturia occurs because of nocturnal urine overproduction. Higher nocturnal bladder capacity index values suggest that nocturia occurs because of decreased nocturnal bladder capacity. RESULTS: There were no statistically significant gender or age related differences in baseline nocturnal micturitions. Nocturia index increased significantly with age (p <0.0001), and values were significantly higher among men than women for all age groups (p = 0.0064). Nocturnal polyuria index increased significantly with age (p <0.0001) and there were no gender differences. For nocturnal bladder capacity index there was a significant decrease with advancing age among men (1.75 greater than 1.16 greater than 0.90) and women (1.53 greater than 1.42 greater than 1.08, P(interaction) = 0.0148). CONCLUSIONS: In younger patients with overactive bladder, decreased nocturnal bladder capacity has a greater role in the pathogenesis of nocturia symptoms, whereas in older patients increased nocturnal urine output has a greater role.

Efficacy and tolerability of tolterodine extended release in male and female patients with overactive bladder.

OBJECTIVES: To evaluate the efficacy and tolerability of tolterodine extended release (ER) in men and women with overactive bladder (OAB). METHODS: We analyzed data from two 12-wk, placebo-controlled trials of tolterodine ER (4mg QD). Patients completed 7-d bladder diaries and rated the urgency sensation associated with each micturition on a 5-point urgency rating scale. Micturitions were categorized by urgency rating: total (1-5), non-OAB (1-2), OAB (3-5), or severe OAB (4-5). Changes in micturitions during 24-h, daytime, and nocturnal intervals were assessed. RESULTS: At baseline, 73% (547 of 745) of men and 57% (539 of 953) of women were continent. By week 12, tolterodine ER (n=848) reduced OAB and severe OAB micturitions during 24-h, daytime, and nocturnal intervals in both sexes compared with placebo (n=850). Adverse event rates were low and similar across treatment and gender. CONCLUSIONS: In men and women with OAB, tolterodine ER reduced OAB and severe OAB micturitions, and was well tolerated.

Tolterodine extended release improves overactive bladder symptoms in men with overactive bladder and nocturia.

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 randomized 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.

Nighttime dosing with tolterodine reduces overactive bladder-related nocturnal micturitions in patients with overactive bladder and nocturia.

OBJECTIVES: To evaluate the efficacy and tolerability of nighttime tolterodine dosing on urgency-related micturitions in patients with overactive bladder (OAB) and nocturia. METHODS: This was a 12-week randomized controlled study of 850 patients given 4 mg tolterodine extended release (TER) or placebo once daily 4 hours or less before bed. Patients with eight or more micturitions/24 hours and a mean of 2.5 episodes/night or more were included. Changes in the number of nighttime and 24-hour micturitions were analyzed by urgency rating per micturition. The urgency per micturition was recorded in 7-day diaries using a 5-point rating scale (score 1 to 5). Each micturition was classified according to the following urgency rating categories: total (1 to 5), non-OAB (1 to 2), or OAB (3 to 5). OAB-related micturitions were further classified as nonsevere (score 3) and severe (score 4 to 5). RESULTS: TER reduced the total number of nocturnal micturitions, but, compared with placebo, this difference was not statistically significant. However, TER did significantly reduce OAB-related and severe OAB-related nocturnal micturitions compared with placebo. TER had no effect on non-OAB micturitions. TER significantly reduced the total, OAB, and severe OAB micturitions during 24-hour and daytime intervals compared with placebo. Significantly more TER-treated than placebo-treated patients reported a treatment benefit and willingness to continue treatment. Adverse events associated with nighttime dosing of TER versus placebo were few. CONCLUSIONS: TER significantly reduced OAB-related micturitions during 24-hour, daytime, and nighttime intervals. TER did not affect normal (non-OAB) micturitions. Nighttime dosing with TER was associated with few adverse events and adverse event-related withdrawals. The 24-hour efficacy of TER was maintained with nighttime dosing.

Efficacy and tolerability of tolterodine extended-release in continent patients with overactive bladder and nocturia.

OBJECTIVE: To evaluate the clinical efficacy and tolerability of tolterodine extended-release (ER) in continent patients with overactive bladder (OAB) and nocturia. PATIENTS AND METHODS: A post hoc analysis was conducted of data from a 12-week, double-blind study of 850 patients randomized to tolterodine ER (4 mg once daily) or placebo, taken within 4 h of going to bed. Patients with a mean of > or = 8 voids/24 h were enrolled, including a mean of > or = 2.5 voids/night. Patients completed 7-day voiding diaries, and for each void an urgency rating was assessed using a 5-point scale (1, none; 5, urgency incontinence); 24-h voids were categorized by urgency rating: total (1-5), non-OAB (1-2), OAB (3-4), and severe OAB (4-5) voids. All adverse events were recorded. RESULTS: The post hoc analysis included 513 patients (243 placebo; 270 tolterodine ER; 58% men) who were continent at baseline; 47% of 24-h voids were classed as non-OAB, and 12% as severe OAB. After 12 weeks of treatment, tolterodine ER significantly reduced mean urgency rating and 24-h OAB, severe OAB, and total voids vs placebo. Tolterodine ER did not affect normal, non-OAB voids, and there were no significant adverse events related to voiding. Other than dry mouth (tolterodine ER, 9% vs placebo, 2%), all the adverse events were reported in <3% of patients; <2% of patients receiving tolterodine ER withdrew because of adverse events. CONCLUSIONS: In continent patients with OAB, tolterodine ER significantly improved urgency rating and reduced 24-h OAB, severe OAB, and total voids, suggesting that it is an effective and well-tolerated treatment option for this subpopulation. More studies are needed to better understand the clinical efficacy of tolterodine ER in this under evaluated group of OAB patients without incontinence.