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Purpose: The efficacy and safety of vibegron, a β 3 -adrenergic receptor agonist, was assessed among men with symptoms of overactive bladder (OAB) receiving pharmacologic treatment for benign prostatic hyperplasia (BPH) in a phase 3 randomized controlled trial., Materials and Methods: Men ≥ 45 years with OAB symptoms and BPH, treated with α-blocker with/without 5α-reductase inhibitors, were randomized 1:1 to vibegron or placebo for 24 weeks. Coprimary end points were change from baseline at week 12 in mean daily micturitions and urgency episodes. Secondary end points were change from baseline at week 12 in mean nightly nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Score‒storage score, and volume voided per micturition. Safety was evaluated via adverse events (AEs)., Results: Of 1105 participants randomized, 965 (87.3%) completed the trial. At week 12, vibegron was associated with significant reductions vs placebo in daily micturitions (least squares mean difference [95% CI], -0.74 [-1.02, -0.46]; P < .0001) and urgency episodes (-0.95 [-1.37, -0.54]; P < .0001). Vibegron was also associated with significant improvements vs placebo at week 12 in nocturia episodes (least squares mean difference, -0.22 [-0.36, -0.09]; P = .002), urge urinary incontinence episodes (-0.80 [-1.33, -0.27]; P = .003), International Prostate Symptom Score‒storage scores (-0.9 [-1.2, -0.6]; P < .0001), and volume voided (15.07 mL [9.13-21.02]; P < .0001). AE rates were similar in vibegron (45.0%) and placebo (39.0%) arms; AEs occurring in ≥ 2% of participants were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), UTI (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%)., Conclusions: In this trial, vibegron met all primary and secondary end points and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.

Aims: Two phase 1 trials were performed in healthy women with the overactive bladder (OAB) syndrome and urodynamically demonstrated detrusor overactivity (DO), with the aim to demonstrate the safety and potential efficacy of URO-902, which comprises a gene therapy plasmid vector expressing the human big potassium channel α subunit., Methods: ION-02 (intravesical instillation) and ION-03 (direct injection) were double-blind, placebo-controlled, multicenter studies without overlap in enrollment between studies. Active doses were administered and evaluated sequentially (lowest dose first) for safety. ION-02 participants received either 5000 µg or 10 000 µg URO-902, or placebo. ION-03 participants received either 16 000 or 24 000 µg URO-902, or placebo, injected directly into the bladder wall using cystoscopy. Primary outcome variables were safety parameters occurring subsequent to URO-902 administration; secondary efficacy variables also were evaluated., Results: Among the safety outcomes, there were no dose-limiting toxicities or significant adverse events (AEs) preventing dose escalation during either trial, and no participants withdrew due to AEs. For efficacy, in ION-02 (N = 21), involuntary detrusor contractions on urodynamics at 24 weeks in patients receiving URO-902 (P < .0508 vs placebo) and mean urgency incontinence episodes in the 5000 µg group (P = .0812 vs placebo) each showed a downward trend. In ION-03 (N = 13), significant reduction versus placebo in urgency episodes (16 000 µg, P = .036; 24 000 µg, P = .046) and number of voids (16 000 µg, -2.16, P = .044; 24 000 µg, -2.73, P = .047) were observed 1 week after injection., Conclusion: Promising safety and efficacy results in these preliminary phase 1 studies suggest gene transfer may be a promising therapy for OAB/DO, warranting further investigation., (© 2020 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.)

Aims: To identify the self-reported treatment goals of patients with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO), determine whether patients achieved their goals following onabotulinumtoxinA treatment, and assess impact of neurogenic disease (multiple sclerosis or spinal cord injury) and/or clean intermittent catheterization (CIC) on goal achievement., Methods: Data from two Phase III studies of onabotulinumtoxinA 200U (n = 227) or placebo (n = 241) in NDO patients (≥14 UI episodes/week; inadequately managed by anticholinergics) were pooled for analysis. At baseline, patients listed their top two qualitative treatment goals, which were distributed into eight subcategories. Six weeks post-treatment, patients rated whether they achieved their goals (5-point Likert scale). The frequency distribution of goals, the proportion of patients who achieved their goals, and goal achievement by etiology and use/non-use of CIC were assessed., Results: At baseline, the most common goals were "be dry" (37.9%), "reduce other urinary symptoms" (26.4%), and "improve quality of life/sleep/emotions" (21.4%). Significantly higher proportions of onabotulinumtoxinA-treated patients achieved their overall goals versus placebo (62.0% vs. 17.2%; P <  0.001). OnabotulinumtoxinA treatment resulted in higher goal achievement in all goal categories, regardless of etiology. CIC use did not negatively impact patients' overall goal achievement; significantly higher proportions of onabotulinumtoxinA-treated patients versus placebo achieved their goals regardless of baseline catheterization use or de novo CIC during the first 6 weeks of the study., Conclusions: The majority of patients with UI due to NDO achieved their self-determined treatment goals following onabotulinumtoxinA 200U therapy, regardless of etiology or CIC use. Neurourol. Urodynam. 35:595-600, 2016. © 2015 The Authors. Neurourology and Urodynamics, published by Wiley Periodicals, Inc., (© 2015 The Authors. Neurourology and Urodynamics, published by Wiley Periodicals, Inc.)

Candidates for onabotulinumtoxinA are generally patients with overactive bladder (OAB) or neurogenic detrusor overactivity (NDO) whose disease is inadequately controlled with behavioral therapy and oral medication. All patients must be willing and able to perform clean intermittent catheterization (CIC). Before the decision to administer onabotulinumtoxinA is made, the clinician should provide counseling to the patient regarding the agent's indications, proposed benefits, risks, and mode of administration. The patient should be aware that onabotulinumtoxinA takes effect after approximately 1-2 weeks and usually lasts for 4-10 months, after which repeat injections will be necessary to maintain effect. Patient preparation may include pre-treatment antibiotics and withdrawal of antiplatelet therapy or anticoagulants. Preparation of the product involves reconstitution in sterile saline and dilution according to the planned dose. Local anesthesia (e.g., bladder instillation of lidocaine) is usually administered, although general anesthesia may be used in certain cases. The injections are performed using a flexible or rigid cystoscope, and the procedure takes approximately 15 min. The initial follow-up visit occurs within 7-14 days, when evidence of adverse effects, including urinary retention, can be evaluated. Repeat injections can be scheduled as needed, but not sooner than 3 months. Currently, the total dose of onabotulinumtoxinA should not exceed 360 U in a 3-month period for all indications, including those outside the urinary tract (i.e., cosmetic, ophthalmologic, etc.). Overall, onabotulinumtoxinA is effective, generally well tolerated, safe, and is relatively simple to provide., (© 2014 Wiley Periodicals, Inc.)

Aims: To evaluate the effect of onabotulinumtoxinA on urodynamic outcomes in patients with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO)., Methods: Results from two pivotal Phase III trials (n = 691) were pooled. MS or SCI patients with NDO, received intradetrusor onabotulinumtoxinA 200 U (n = 227), 300 U (n = 223), or placebo (n = 241). Change from baseline in UI episodes/week (Week 6), maximum cystometric capacity (MCC), maximum detrusor pressure at first involuntary detrusor contraction (IDC) (PdetmaxIDC), volume at first IDC (VpmaxIDC), and detrusor compliance (DC) were measured., Results: OnabotulinumtoxinA significantly increased MCC overall (+153.6 ml with 200 U vs. +11.9 ml with placebo). Over 60% of onabotulinumtoxinA-treated patients had no IDC at Week 6; in patients with an IDC at Week 6, VpmaxIDC improved (+183.4 ml with 200 U vs. +17.5 ml with placebo), and PdetmaxIDC decreased (-32.4 cmH2O with 200 U vs. +1.1 cmH2O with placebo). OnabotulinumtoxinA-treated patients had a significant increase in DC (+59.8 ml/cmH2O with 200 U vs. -5.2 with placebo). Urodynamic improvements were comparable in patients regardless of baseline DC and corresponded with significant reductions in UI episodes/week for both onabotulinumtoxinA doses versus placebo, with no clinically relevant differences between 200 and 300 U groups. Most common adverse event was urinary tract infection (UTI); complicated UTIs were low across all treatment groups. In patients not catheterizing at baseline, a dose-dependent increase in post-void residual urine was observed at Week 2 following onabotulinumtoxinA treatment., Conclusions: OnabotulinumtoxinA significantly improved urodynamic outcomes in NDO patients, even in those with low baseline DC, and corresponded with improvements in UI episodes. Both doses of onabotulinumtoxinA were well tolerated., (© 2013 Wiley Periodicals, Inc.)

Aims: We assessed the effects of onabotulinumtoxinA (BOTOX®) on clinical and urodynamic variables in patients with idiopathic overactive bladder (OAB) and urinary urgency incontinence (UUI) with or without detrusor overactivity (DO), inadequately managed with anticholinergics., Methods: Three hundred thirteen patients with OAB were randomized to double-blind intradetrusor injection with placebo (n = 44) or 1 of 5 onabotulinumtoxinA doses (50-300 U; n = 269). Primary efficacy variable was change from baseline in UUI episodes/week at week 12. Urodynamic assessments at baseline and weeks 12 and 36 included maximum cystometric capacity (MCC) and volume at first involuntary detrusor contraction (IDC)., Results: 76.0% of patients had baseline DO. Changes from baseline in MCC and volume at first IDC with onabotulinumtoxinA ≥100 U were superior to placebo at week 12, generally decreasing by week 36. Significant dose-dependent increases in MCC were observed for all onabotulinumtoxinA doses at week 12, and for 150, 200, and 300 U at week 36. Data suggested a dose-response relationship. At week 12 on diary, 15.9% of placebo and 29.8-57.1% of onabotulinumtoxinA 50-300 U recipients, respectively, did not demonstrate UUI. OnabotulinumtoxinA doses >150 U were more commonly associated with post-void residual urine volumes >200 ml., Conclusions: Improvements in urodynamic parameters and clinical outcomes generally trended together following onabotulinumtoxinA treatment. This therapy improved key urodynamic parameters in patients with idiopathic OAB and UUI, with no differences in outcomes between those with and those without baseline DO. Therefore, successful idiopathic OAB treatment with onabotulinumtoxinA does not appear to be related to pretreatment finding of DO., (Copyright © 2011 Wiley-Liss, Inc.)

The primary pharmacological therapy for overactive bladder syndrome is muscarinic receptor antagonists. Muscarinic receptor blockade is effective in decreasing the symptoms of urinary urgency and urgency incontinence, but can be associated with troublesome complications, such as dry mouth, blurred vision, constipation and CNS side effects. Trospium chloride, an antimuscarinic medication, has been available in Europe for > 20 years and has recently been approved by the FDA for the treatment of overactive bladder. Trospium chloride is a quaternary amine that is minimally metabolised, not highly protein bound and, importantly, has not been demonstrated to cross the unaltered blood-brain barrier in healthy volunteers. Some characteristics of this unique antimuscarinic agent and the European experience with trospium chloride are reviewed in this article.