fesoterodine and Urinary-Bladder--Neurogenic

Neurogenic detrusor overactivity (NDO) can damage the upper urinary tract leading to chronic renal impairment. Antimuscarinic therapy is used to improve urinary incontinence and protect the upper urinary tract in patients with NDO.. This study investigated safety and efficacy of fesoterodine, a muscarinic receptor antagonist, in 6‒<18-year-old patients with NDO (NCT01557244).. This open-label phase 3 study included 2 pediatric cohorts. Patients in Cohort 1 (bodyweight >25 kg) were randomized to fesoterodine 4 or 8 mg extended-release tablets or oxybutynin XL tablets administered over the 12-week active comparator-controlled phase. The safety extension phase evaluated fesoterodine 4 and 8 mg for a further 12 weeks, with patients in the oxybutynin arm allocated to fesoterodine 4 or 8 mg. Patients in Cohort 2 (bodyweight ≤25 kg) were randomized to fesoterodine 2 or 4 mg extended-release beads-in-capsule (BIC) administered over a 12-week efficacy phase and 12-week safety extension phase. Patients with stable neurologic disease and clinically or urodynamically proven NDO were included. The primary endpoint was change from baseline to Week 12 in maximum cystometric bladder capacity (MCC). Secondary efficacy endpoints included detrusor pressure at maximum bladder capacity, bladder volume at first involuntary detrusor contraction, bladder compliance, and incontinence episodes. Safety endpoints included adverse event incidence, and specific assessments of cognition, behavior and vision. The pharmacokinetics of 5-hydroxymethyl tolterodine (5-HMT; fesoterodine's active metabolite) was determined using population-pharmacokinetic analysis.. In Cohort 1 (n = 124), fesoterodine 4 and 8 mg treatment resulted in significant increases from baseline in the primary endpoint of MCC at Week 12. In Cohort 2 (n = 57), fesoterodine 2 and 4 mg BIC treatment resulted in improvements in MCC from baseline. Fesoterodine 4 and 8 mg and fesoterodine 4 mg BIC led to improvements in some secondary efficacy endpoints. The most common treatment-related adverse reactions were gastrointestinal effects, such as dry mouth, which occurred more frequently with oxybutynin than fesoterodine. No detrimental effects on visual accommodation or acuity, or on cognitive function or behavior were observed.. These safety and efficacy results are consistent with limited published data on fesoterodine treatment in pediatric populations with overactive bladder or NDO. Study limitations include the lack of placebo control and the small sample size, which limits the ability to make formal efficacy comparisons and detect rare adverse reactions.. Fesoterodine has a favorable benefit-risk profile in 6‒<18-year-old patients with NDO and may represent an additional option for pediatric NDO treatment.

Topics: Adolescent; Child; Humans; Mandelic Acids; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics

Managing and preventing risk factors associated with cardiovascular and cerebrovascular impairment is well studied in able-bodied individuals. However, individuals with spinal cord injury (SCI) at or above the spinal segment T6 are prone to experience autonomic dysreflexia (AD) but also to suffer from neurogenic detrusor overactivity (NDO). Treatment of NDO would not only improve lower urinary tract function but could also reduce the severity and frequency of life-threatening episodes of AD. Fesoterodine, an antimuscarinic drug, has been successfully employed as a first-line treatment for detrusor overactivity in individuals without an underlying neurological disorder. Thus, our aim is to investigate the efficacy of fesoterodine to improve NDO and ameliorate AD in individuals with SCI.. This phase II, open-label exploratory, non-blinded, non-randomised, single-centre study will investigate the efficacy of fesoterodine to improve NDO and ameliorate AD in individuals with chronic SCI at or above T6. During screening, we will interview potential candidates (with a previous history of NDO and AD) and assess their injury severity. At baseline, we will perform cardiovascular and cerebrovascular monitoring (blood pressure (BP), heart rate and cerebral blood flow velocity) during urodynamics (UDS) and 24-hour ambulatory BP monitoring (ABPM) during daily life to assess severity and frequency of AD episodes (ie, maximum increase in systolic BP). The primary outcome is a reduction of artificially induced (during UDS) and spontaneous (during daily life) episodes of AD as a display of treatment efficacy. To answer this, we will repeat UDS and 24-hour ABPM during the last cycle of the treatment phase (12 weeks overall, ie, three cycles of 4 weeks each). At the end of each treatment cycle, participants will be asked to answer standardised questionnaires (AD symptoms and quality of life) and present bladder and bowel diaries, which will provide additional subjective information.. The University of British Columbia Research Ethics Boards (H15-02364), Vancouver Coastal Health Research Institute (V15-02364) and Health Canada (205857) approved this study. The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials and CONsolidated Standards Of Reporting Trials statements.. NCT02676154; Pre-results.

Topics: Adult; Autonomic Dysreflexia; Benzhydryl Compounds; Blood Flow Velocity; Blood Pressure; Cerebrovascular Circulation; Heart Rate; Humans; Muscarinic Antagonists; Quality of Life; Spinal Cord Injuries; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

to evaluate the effectiveness of fesoterodine for the prevention of autonomic dysreflexia (AD) in patients with neurogenic bladder dysfunction (NBD) after spinal cord injury (SCI).. a total of 53 patients with AD were included in the study. In the main group (n=33) patients received fesoterodine 4 mg per day for 12 weeks as a treatment for neurogenic bladder dysfunction and prevention of AD. In the control group (n=20), patients were monitored for 12 weeks without specific treatment. The assessment was based on the results of ADFSCI and NBSS questionnaires, daily blood pressure monitoring with the completion of a self-observation diary, cystometry with simultaneous monitoring of blood pressure and heart rate.. In the main group there was a significant decrease in episodes and severity of AD according to ADFSCI questionnaire and an improvement in the quality of life according to NBSS questionnaire compared to the control group (p<0.001). Also, in the main group, the number of episodes of AD and systolic blood pressure decreased. The maximum bladder capacity and bladder compliance increased (p<0.001), and the maximum detrusor pressure and systolic blood pressure when the cystometric capacity was reached, decreased significantly (p<0.001) in the main group compared in comparison with the control group.. Fesoterodine at a dosage of 4 mg for 12 weeks reduced the severity of symptoms of AD in patients with SCI and NBD, which was manifested by the stabilization of blood pressure and a decrease in the number of episodes of AD, which significantly improved the quality of life. Also, the drug led to a significant improvement in urodynamic parameters during cystometry, in the form of a decrease in detrusor pressure and an increase in cystometric capacity. We can conclude that fesoterodine is effective in the prevention of AD in patients with NBD after SCI.

Topics: Autonomic Dysreflexia; Humans; Quality of Life; Spinal Cord Injuries; Urinary Bladder; Urinary Bladder, Neurogenic; Urodynamics

Antimuscarinic drugs are the first-line choice in the treatment of patients with neurogenic Detrusor Overactivity (nDO). Fesoterodine fumarate is the newest antimuscarinic drug. Limited data are published about the use of fesoterodine fumarate in patients suffering from neurogenic lower urinary tract dysfunction. Our study aims to determine the efficacy of fesoterodine fumarate on patients with nDO due to spinal cord lesion or multiple sclerosis (MS).. This is an open-label prospective interventional study. Eligible patients were 18-80 years old with SCL or MS and nDO confirmed by a urodynamic study (UDS). At baseline, patients underwent a UDS to confirm nDO. Quality of life (QoL) was assessed by the Short-Form (SF) Qualiveen questionnaire. Patients received fesoterodine 8 mg/day for 3 months and were re-evaluated with UDS and SF-Qualiveen. The primary endpoint was the confirmation of the maximum detrusor pressure (P. One hundred and twenty-four patients completed the study. Ninety-five of them (76.6%) had SCL, while 29 (23.4%) had MS. P. Fesoterodine fumarate (8 mg) is an efficacious drag in patients with SCL and MS, as it significantly decreases the detrusor pressure, increases the bladder capacity and compliance, and improves the QoL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Botulinum Toxins, Type A; Humans; Middle Aged; Multiple Sclerosis; Prospective Studies; Quality of Life; Spinal Cord; Spinal Cord Injuries; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics; Young Adult

Topics: Benzhydryl Compounds; Humans; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

To examine the urodynamic effects of fesoterodine on neurogenic detrusor overactivity and/or low compliance bladder.. A total of 77 patients (52 men, 25 women; aged 61.6 ± 20.3 years) were given fesoterodine 4-8 mg/day and prospectively followed for 12 weeks. The primary end-point variable was change in the maximum cystometric capacity on urodynamic study. The secondary end-point was to assess the number of patients whose neurogenic detrusor overactivity disappeared, and the changes in the urodynamic parameters, lower urinary tract symptoms questionnaires and the 3-day frequency volume chart parameters after the treatment.. A total of 13 patients (16.9%) withdrew because of adverse events (dry mouth or blurred vision), and four patients dropped out for unknown reasons. Finally, 60 patients completed the study. Bladder capacity at first desire to void, maximum cystometric capacity and bladder compliance increased by 29.2 mL, 79.9 mL and 22.2 mL/cm H. Fesoterodine seems to be a valid treatment option for neurogenic detrusor overactivity and/or low compliance bladder in neurogenic bladder patients.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Female; Humans; Male; Middle Aged; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

A low-pressure bladder in children with neuropathic bladder dysfunction can be achieved using anticholinergic medication. Due to the significant side effects of oral oxybutynin, our patients are treated with daily intravesical oxybutynin instillations. Newer oral anticholinergic medication, such as fesoterodine, claim to have fewer side effects in a once daily formulation. Because once-daily oral intake is easier than performing twice-daily intravesical instillations, we studied the effects of switching from intravesical oxybutynin to oral fesoterodine and compared the clinical response, urodynamic parameters and side effects.. Twenty children (11 girls, 9 boys, 4-17 years) with neuropathic bladder dysfunction who perform clean intermittent catheterization and use intravesical oxybutynin instillations twice daily were included in this prospective study. Voiding diaries, a behavioural checklist, urodynamic investigations, vital signs and blood samples were evaluated at baseline during treatment with intravesical oxybutynin and repeated after 40 days of oral fesoterodine.. Out of 20, 13 (65%) children showed an identical objective dryness (pad-test), 2 (10%) improved and 5 (25%) got worse. Seven (35%) children reported equal dryness, 7 (35%) reported improvement and 6 (30%) reported that it got worse. From a urodynamic perspective, 13 (65%) children remained identical, 3 (15%) improved and 4 (20%) got worse. Four (20%) children reported a light to moderate dry mouth, 1 (5%) a headache, 1 (5%) behavioural changes during fesoterodine administration, 1 (5%) an increased appetite, 1 (5%) nausea and 1 (5%) hot flushes.. The urodynamics after 40 days of fesoterodine were in 16 (80%) identical or better and could be a safe alternative for oxybutynin instillations in children with neuropathic bladder dysfunction.

Topics: Administration, Intravesical; Administration, Oral; Adolescent; Benzhydryl Compounds; Child; Child, Preschool; Drug Substitution; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Prospective Studies; Urinary Bladder, Neurogenic

In spinal cord injury, onset of detrusor overactivity (DO) is detrimental for quality of life (incontinence) and renal risk. Prevention has only been achieved with complex sophisticated electrical neuromodulation techniques.. To assess the efficacy of early fesoterodine fumarate (FF) administration in preventing bladder overactivity in a spinal cord transected (SCT) rat model.. 33 Sprague-Dawley rats were allocated to 6 groups-Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10. FF was continuously administered. Cystometry was undertaken 6 weeks after SCT in awake rats recording intermicturition pressure (IMP), baseline pressure, threshold pressure (Pthres) and maximum pressure (Pmax). Normal controls and SCT controls were initially compared using the Mann-Whitney U tests in order to confirm the SCT effect on cystometric parameters. The comparisons in cystometric and metabolic cage parameters between SCT controls and treated rats were done using post-hoc Dunn's tests for Kruskal-Wallis analysis. Statistical testing was conducted at the two-tailed α-level of 0.05.. Pressure parameters were significantly higher in SCT control group compared to normal controls. Six weeks after SCT, IMP was significantly lower in low dose treated group than in SCT controls. Pmax was significantly lower in 3 treated groups compared to SCT controls. Pthres was significantly lower in full time treated groups than in SCT controls.. Early administration of FF modulates bladder overactivity in a SCT rat model. Whereas short-term prevention has been demonstrated, the long-term should be further analyzed. Clinical application of these results should confirm this finding through randomized research protocols.

Topics: Animals; Benzhydryl Compounds; Disease Models, Animal; Female; Muscarinic Antagonists; Pressure; Rats; Spinal Cord Injuries; Time Factors; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive