Franklin Sun

Tolterodine Treatment Improves Storage Symptoms Suggestive of Overactive Bladder in Men Treated With α-Blockers

BACKGROUND Some men receiving alpha-blocker therapy for lower urinary tract symptoms report persistent storage symptoms suggestive of overactive bladder (OAB). OBJECTIVE To evaluate the efficacy of tolterodine extended release (ER) in men on alpha-blocker therapy. DESIGN, SETTING, AND PARTICIPANTS This double-blind trial included men aged > or = 40 yr with frequency, urgency, and at least moderate problems reported on the Patient Perception of Bladder Condition (PPBC), despite being on a stable dose of alpha-blocker for > or = 1 mo. INTERVENTIONS Subjects were randomized to tolterodine ER 4 mg per day or placebo for 12 wk while continuing their prescribed alpha-blocker therapy. MEASUREMENTS At baseline and week 12, subjects completed the PPBC, International Prostate Symptom Score (IPSS), Overactive Bladder Questionnaire (OAB-q), and 5-d bladder diaries using the five-point Urinary Sensation Scale (USS). Frequency-urgency sum was defined as the sum of USS ratings for all micturitions. RESULTS AND LIMITATIONS PPBC improvement from baseline to week 12 was reported by 63.6% and 61.6% of subjects receiving tolterodine ER plus alpha-blocker and placebo plus alpha-blocker, respectively; this treatment difference, which was the primary end point, was not statistically significant (p>0.6699). At week 12, subjects receiving tolterodine ER plus alpha-blocker had significantly greater improvements versus placebo plus alpha-blocker in 24-h micturitions (-1.8 vs -1.2; p=0.0079) and daytime micturitions (-1.3 vs -0.8; p=0.0123); 24-h urgency episodes (-2.9 vs -1.8; p=0.0010), daytime urgency episodes (-2.2 vs -1.4; p=0.0017), and nocturnal urgency episodes (-0.5 vs -0.3; p=0.0378); frequency-urgency sum (-7.8 vs -5.1; p=0.0065); IPSS storage subscale (-2.6 vs -2.1; p=0.0370); and OAB-q symptom bother scale (-17.9 vs -14.4; p=0.0086) and coping domain (15.4 vs 12.4; p=0.0491). Acute urinary retention requiring catheterization occurred in < 1% of either group. There were no clinically meaningful changes in postvoid residual volume or maximum urinary flow rate. CONCLUSIONS Men with bothersome OAB symptoms despite continued alpha-blocker therapy showed significantly greater improvements in diary variables, IPSS Storage scores, and symptom bother when receiving additional tolterodine ER versus placebo plus alpha-blocker.

Effect of fesoterodine in vulnerable elderly subjects with urgency incontinence: A double-blind, placebo controlled trial

PURPOSE We evaluated the efficacy and safety of flexible dose fesoterodine in medically complex vulnerable elderly subjects with urgency urinary incontinence. MATERIALS AND METHODS In this 12-week, randomized, double-blind, flexible dose, placebo controlled trial, subjects were community dwelling men and women 65 years old or older. Subjects had scores of 3 or more on the VES-13 (Vulnerable Elders Survey) and 20 or more on the MMSE (Mini-Mental State Examination), and 2 to 15 urgency urinary incontinence episodes and 8 or more micturitions per 24 hours on 3-day baseline diaries. Subjects randomized to fesoterodine received 4 mg once daily for 4 weeks and could then increase to 8 mg based on discussion with the investigator. Subjects receiving 8 mg could decrease the dose to 4 mg at any time (sham escalation and de-escalation for placebo). The primary outcome measure was change in daily urgency urinary incontinence episodes. Secondary outcomes included changes in other diary variables and patient reported quality of life measures. Safety evaluations included self-reported symptoms and post-void residual volume. RESULTS A total of 562 patients were randomized (mean age 75 years, 50.4% age 75 years or greater). Subjects had high rates of comorbidities, polypharmacy and functional impairment. At week 12 the fesoterodine group had significantly greater improvements in urgency urinary incontinence episodes per 24 hours (-2.84 vs -2.20, p = 0.002) and most other diary variables and quality of life, as well as a higher diary dry rate (50.8% vs 36.0%, p = 0.002). Adverse effects were generally similar to those of younger populations including risk of urinary retention. CONCLUSIONS To our knowledge this is the first antimuscarinic study in a community based, significantly older, medically complex elderly population with urgency urinary incontinence. Flexible dose fesoterodine significantly improved urgency urinary incontinence episodes and other outcomes vs placebo, and was generally well tolerated.

Randomized, Double-blind, Placebo-controlled Trial of Flexible-dose Fesoterodine in Subjects With Overactive Bladder

OBJECTIVES To evaluate the efficacy and tolerability of flexible-dose fesoterodine vs placebo in subjects with overactive bladder (OAB). METHODS In a 12-week double-blind trial, subjects were randomized to fesoterodine 4 mg or placebo once daily, taken within 4 hours of bedtime. At week 2, subjects could increase the fesoterodine dose to 8 mg (sham escalation for placebo). Subjects completed 3-day bladder diaries, Patient Perception of Bladder Condition, and Urgency Perception Scale at baseline and weeks 2, 6, and 12 as well as OAB Questionnaire at baseline and week 12. RESULTS Of 883 subjects, 63% and 73% of the fesoterodine (n = 438) and placebo (n = 445) groups, respectively, opted for dose escalation. Week 12 improvements from baseline in total micturitions, urgency episodes, urgency urinary incontinence episodes, frequency-urgency sum, and all OAB Questionnaire scales and domains, but not nocturnal micturitions or nocturnal urgency episodes, were significantly greater with fesoterodine than placebo (all P <.05). Treatment differences in micturitions and frequency-urgency sum were significant by week 2 and in urgency urinary incontinence and urgency episodes by week 6. Significantly greater percentages of subjects taking fesoterodine had improved Patient Perception of Bladder Condition and Urgency Perception Scale scores at weeks 2, 6, and 12 (P <.05). Dry mouth (fesoterodine, 26%; placebo, 8%) and constipation (fesoterodine, 11%; placebo, 6%) were the most common adverse events. In both groups, 87% of the subjects completed the trial; 8% and 5% of the fesoterodine and placebo groups, respectively, discontinued because of an adverse event. CONCLUSIONS Flexible-dose fesoterodine was efficacious and generally well tolerated for treatment of OAB symptoms.

Single‐Pill Therapy in the Treatment of Concomitant Hypertension and Dyslipidemia (The Amlodipine/Atorvastatin Gemini Study)

The Gemini Study was a 14‐week, open‐label, noncomparative, office‐based, multicenter trial to evaluate single‐pill therapy in the treatment of concomitant hypertension and dyslipidemia. In addition to recommending lifestyle modifications, eight dosage strengths of amlodipine/atorvastatin single pill (5/10, 5/20, 5/40, 5/80,10/10,10/20,10/40, and 10/80 mg) were electively titrated to improve blood pressure and lipid control. A total of 1220 patients with uncontrolled hypertension at baseline received study medication. At baseline, mean blood pressure was 146.6/87.9 mm Hg and mean low‐density lipoprotein cholesterol concentration was 152.9 mg/dL. At study end, 57.7% of patients had achieved both their blood pressure and low‐density lipoprotein cholesterol goals (51.9% of patients with uncontrolled low‐density lipoprotein cholesterol at baseline). The mean dose of study medication at end point was amlodipine component 7.1 mg and atorvastatin component 26.2 mg. Fifty‐eight patients (4.8%) discontinued therapy due to adverse events. Single‐pill therapy is effective in reducing both blood pressure and lipid levels and in helping patients achieve goals for both hypertension and dyslipidemia.

A randomized, placebo-controlled trial to evaluate the efficacy, safety, and pharmacodynamic interaction of coadministered amlodipine and atorvastatin in 1660 patients with concomitant hypertension and dyslipidemia : The respond trial

Guidelines stress the importance of the simultaneous management of multiple cardiovascular risk factors. This can in part be achieved by coadministration of lipid‐lowering and antihypertensive treatments. Potential pharmacodynamic interaction between drugs should be investigated as part of developing single‐pill combinations. The Respond trial assessed whether combining amlodipine to treat hypertension and atorvastatin to treat dyslipidemia affected the action of either monotherapy. A total of 1660 hypertensive patients with dyslipidemia received 1 of 15 combinations of amlodipine (placebo, 5, or 10 mg) and atorvastatin (placebo, 10, 20, 40, or 80 mg) in a 3 × 5 factorial randomized, placebo‐controlled design. At 8 weeks, combination‐treated patients experienced dose‐related and statistically significant reductions in systolic blood pressure, low‐density lipoprotein cholesterol, and Framingham risk score. Overall, coadministered atorvastatin and amlodipine was well tolerated and without adverse pharmacodynamic interaction; combination treatment did not affect the low‐density lipoprotein cholesterol‐lowering efficacy and safety of atorvastatin, or the systolic blood pressure‐lowering efficacy and safety of amlodipine.

Add-on fesoterodine for residual storage symptoms suggestive of overactive bladder in men receiving α-blocker treatment for lower urinary tract symptoms.

Study Type – Therapy (RCT)

Combined Effects of Behavioral Intervention and Tolterodine in Patients Dissatisfied With Overactive Bladder Medication

PURPOSE We assessed the effect of tolterodine extended release plus behavioral intervention on treatment satisfaction and bladder diary variables in patients with overactive bladder who had been previously treated and were dissatisfied with tolterodine or other antimuscarinics. MATERIALS AND METHODS This 16-week, multicenter, open label study included eligible patients 18 years old or older who reported overactive bladder symptoms 3 months or greater in duration, 8 or greater micturitions and 2 or greater urgency related micturitions per 24 hours, and 1 or greater urgency urinary incontinence episodes in a 5-day bladder diary at baseline as well as dissatisfaction with prior antimuscarinic medication. Patients received tolterodine extended release plus self-administered behavioral intervention, consisting of an educational pamphlet with verbal reinforcement, for 8 weeks. Satisfied patients continued with this therapy and dissatisfied patients received tolterodine extended release plus individualized behavioral intervention, consisting of in-depth interaction with a clinician to refine behavioral techniques, for 8 weeks thereafter. Patients rated treatment satisfaction at weeks 8 and 16, and completed a 5-day bladder diary at weeks 4, 8, 12 and 16, respectively. RESULTS At weeks 8 and 16, 346 and 357 patients or 91% of the total cohort reported being at least a little satisfied with tolterodine extended release plus behavioral intervention, including 201 (53%) and 252 (64%), respectively, who were very satisfied. Of the 33 patients who were dissatisfied at week 8, 25 (76%) reported treatment satisfaction at week 16 after individualized behavioral intervention. Compared with baseline all bladder diary variables were significantly improved by week 4 (p <0.0001). Patients who were dissatisfied with prior tolterodine or other antimuscarinic treatment reported similar results. CONCLUSIONS Tolterodine extended release plus behavioral intervention resulted in high treatment satisfaction and improved bladder diary variables in patients who had previously been treated and were dissatisfied with tolterodine or other antimuscarinics.

Effects of voluntary dose escalation in a placebo-controlled, flexible-dose trial of fesoterodine in subjects with overactive bladder.

To characterize the response to fesoterodine treatment for overactive bladder (OAB) in subjects who did or did not choose to dose escalate in a flexible‐dose study.

Superiority of fesoterodine 8 mg vs 4 mg in reducing urgency urinary incontinence episodes in patients with overactive bladder: results of the randomised, double-blind, placebo-controlled EIGHT trial

To assess the superiority of fesoterodine 8 mg vs 4 mg for improvement in urgency urinary incontinence (UUI) episodes and other diary variables, diary‐dry rate (proportion of patients with >0 UUI episodes on baseline diary and 0 UUI episodes on post‐baseline diary), and improvements in measures of symptom bother, health‐related quality of life (HRQL), and other patient‐reported outcomes (PROs).

Effects of tolterodine ER on patient-reported outcomes in sexually active women with overactive bladder and urgency urinary incontinence

ABSTRACT Objective: To assess the effects of tolterodine extended release (ER) on patient-reported outcomes (PROs) in sexually active women with overactive bladder (OAB) and urgency urinary incontinence (UUI). Research design and methods: This multicenter, double-blind, placebo controlled trial included 411 women aged ≥18 years reporting OAB symptoms for ≥3 months; ≥8 micturitions per 24 hours (including ≥0.6 UUI episodes and ≥3 OAB micturitions) in 5-day bladder diaries at baseline, and being in a sexually active relationship for ≥6 months. Subjects randomized to placebo or tolterodine ER completed validated OAB- or incontinence-specific questionnaires, including the Patient Perception of Bladder Condition (PPBC), Overactive Bladder Questionnaire (OAB-q), Urgency Perception Scale (UPS), and the Incontinence Impact Questionnaire (IIQ) at baseline and week 12, as well as the Perception of Treatment Benefit and Treatment Satisfaction questions at week 12. This study is registered with ClinicalTrials.gov (identifier: NCT00143481) Results: The mean age of enrolled women was approximately 48 years. Compared with placebo, the tolterodine ER group reported significant baseline to week 12 improvements in PPBC responses (p = 0.0048); OAB-q Symptom Bother, total Health-Related Quality of Life (HRQL), and HRQL domain scores (all p < 0.05); IIQ Emotional Health domain scores (p < 0.05); proportions of subjects reporting treatment benefit (79 vs. 54%; p < 0.0001) and satisfaction (78 vs. 59%; p < 0.0001). Improvements on the UPS were not significantly different. Conclusions: Tolterodine ER treatment was associated with improvements in multiple OAB- and incontinence-specific PROs in a sexually active, relatively young, and racially diverse population of women. The findings provide clinicians with new insights into the impact of OAB and its treatment on HRQL in this population, which has been underrepresented in previous OAB studies. Study limitations include a potential underestimation of the impact of OAB symptoms resulting from the exclusion of women who may not be sexually active because of their urinary symptoms. Trial registration: ClinicalTrials.gov identifier: NCT00143481.