mirabegron and Urinary-Bladder--Overactive

The aim of this study was to indirectly compare the efficacy and safety of mirabegron and vibegron in patients with overactive bladder.. A systematic search was performed on Pubmed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials databases to identify studies from the date of database inception to January 1, 2022. All randomized controlled trials comparing mirabegron or vibegron with tolterodine, imidafenacin, or placebo were eligible. One reviewer extracted data, and a second reviewer checked. Included trials were assessed for similarity, and networks were developed using Stata 16.0 software. Mean differences for continuous variables and odds ratios for dichotomous variables together with their 95% confidence intervals (CIs) were used to rank treatments and compare the differences, respectively.. A total of 11 randomized controlled trials and 10 806 patients were included. For each outcome, results for all licensed treatment doses were included. Both vibegron and mirabegron were more efficacious than placebo at reducing the frequency of micturition, incontinence, urgency, urgency incontinence, and nocturia. Vibegron was more efficacious than mirabegron in reducing mean voided volume/micturition (95% CI [5.15, 14.98]). Safety outcomes for vibegron and mirabegron were similar to those in the placebo group, except for mirabegron, which had a higher risk of nasopharyngitis and cardiovascular adverse events than placebo.. Both drugs seem to be comparable and well tolerated, particularly as direct comparisons are not available. However, vibegron may be more effective than mirabegron in reducing mean voided volume.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Double-Blind Method; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome; Urinary Bladder, Overactive

The goal of this meta-analysis was to determine the efficacy and safety of medication for treating overactive bladder (OAB) in patients with Parkinson's disease (PD).. Papers containing predefined key terms were searched in the PubMed, Embase, Web of Science, and Cochrane Library databases up to December 2021 to collect randomized double-blind placebo-controlled trials (RCTs). The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. Two reviewers independently assessed the risk of bias using the modified Jadad scale and Cochrane risk-of-bias tool. The GRADEpro GDT was employed to evaluate the strength of evidence based on the findings of this meta-analysis.. We eventually included four RCTs involving 313 patients (163 patients in the medication group and 150 patients in the placebo group). Of these, the therapeutic agent in two RCTs was mirabegron (121 and 106 patients and controls, respectively, representing 3/4 -2/3 of the patients). The results showed that the number of micturition episodes per 24 h (MD -1.33; 95% CI -2.30 to -0.36; p = 0.007), the number of nocturia episodes per 24 h (MD -0.33; 95% CI -0.58 to -0.08; p = 0.009) and the number of urinary incontinence episodes per 24 h (MD -0.72; 95% CI -1.32 to -0.12; p = 0.02) were significantly lower in the medication group than in the placebo group. The OAB symptom score (MD -2.84; 95% CI -4.67 to -1.00; p = 0.002) and quality of life score (MD 15.15; 95% CI 12.33 to 17.96; p < 0.0001) of the medication group were significantly improved compared with those of the placebo group. However, no significant difference in the daily frequency of urinary urgency episodes was identified between the medication group and the placebo group (MD -0.79; 95% CI -1.71 to 0.14; p = 0.09). There were no significant differences between the two groups in terms of drug-related adverse events (OR 1.69; 95% CI 0.41 to 6.99; p = 0.47), especially in PD patients receiving mirabegron therapy.. Medication was effective for OAB symptoms in patients with PD, and patients tolerated adverse events well.

Topics: Acetanilides; Double-Blind Method; Humans; Parkinson Disease; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Urinary Bladder, Overactive

OBJECTIVE: This review aimed to establish the comparison between mirabegron and antimuscarinic agents through the improvement of the urodynamic study (UDS) parameter among overactive bladder (OAB) populations. MATERIALS AND METHODS: The PRISMA checklist and procedure were utilized to standardize our review of studies from scientific databases published between January 2013 and May 2022 in accordance with the applied eligibility criteria. This study mainly focused on UDS parameter improvement; hence, baseline and follow-up completion were mandatory to be included. The quality of each included study was assessed with the Cochrane risk-of-bias tool in RevMan 5.4.1. RESULTS: We included a total of 5 clinical trials encompassing 430 clinically confirmed OAB individuals. Our meta-analysis demonstrated that the improvement of maximum urinary flow rate (Qmax) was more apparent in the mirabegron arm [mean difference (MD), 1.78 (1.31, 2.26); p<0.05] compared to antimuscarinics arm [MD, 0.02 (-2.53, 2.57); p>0.05) as analyzed in random-effect model (REM) analysis within 95% CI. Similar outcomes were also observed on the other UDS parameters related to the bladder's storage function, e.g., post-void residual (PVR) and detrusor overactivity (DO) cases, with most of the MDs favoring mirabegron. CONCLUSIONS: Mirabegron is superior in improving most of the UDS parameter outcomes compared to the antimuscarinics agents though the current guideline should always refer to symptoms improvement. Emphasizing the role of UDS parameter measurements to objectively confirm a therapeutic effect should be considered in the upcoming studies.

Topics: Acetanilides; Humans; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Urological Agents

 To compare the use of mirabegron with anticholinergics drugs for the treatment of overactive bladder (OB)..  Systematic searches were conducted in EMBASE, PUBMED, Cochrane, and LILACS databases from inception to September 2021. We included RCTs, women with clinically proven OB symptoms, studies that compared mirabegron to antimuscarinic drugs, and that evaluated the efficacy, safety or adherence..  RevMan 5.4 was used to combine results across studies. We derived risk ratios (RRs) and mean differences with 95% CIs using a random-effects meta-analytic model. Cochrane Collaboration Tool and GRADE was applied for risk of bias and quality of the evidence..  We included 14 studies with a total of 10,774 patients. Fewer total adverse events was reported in mirabegron group than in antimuscarinics group [RR 0.93 (0.89-0.98)]. The risk of gastrointestinal tract disorders and dry mouth were lower with mirabegron [RR 0,58 (0.48-0.68); 9375 patients; RR 0.44 (0.35-0.56), 9375 patients, respectively]. No difference was reported between mirabegron and antimuscarinics drugs for efficacy. The adherence to treatment was 87.7% in both groups [RR 0.99 (0.98-1.00)]..  Mirabegron and antimuscarinics have comparable efficacy and adherence rates; however, mirabegron showed fewer total and isolated adverse events..  Comparar o uso de mirabegrom com anticolinérgicos para o tratamento da bexiga hiperativa (BH)..  Buscas sistemáticas foram realizadas nas bases de dados EMBASE, PUBMED, Cochrane e LILACS desde o início até setembro de 2021. Incluímos ECR, mulheres com sintomas de BH clinicamente comprovados, estudos que compararam mirabegrom a medicamentos antimuscarínicos e avaliaram a eficácia, segurança ou adesão..  RevMan 5.4 foi usado para combinar os resultados entre os estudos. Derivamos razões de risco (RRs) e diferenças médias com intervalo de confiança (IC) de 95% usando um modelo meta-analítico de efeitos aleatórios. Cochrane Collaboration Tool e GRADE foi aplicado para risco de viés e qualidade da evidência. SíNTESE DOS DADOS:  Foram incluídos 14 estudos com um total de 10.774 pacientes. Menos eventos adversos totais foram relatados no grupo mirabegrom do que no grupo antimuscarínicos [RR: 0,93 (0,89–0,98)]. O risco de distúrbios do trato gastrointestinal e boca seca foram menores com mirabegrom [RR: 0,58 (0,48–0,68); 9.375 pacientes; RR: 0,44 (0,35–0,56), 9.375 pacientes, respectivamente]. Nenhuma diferença foi relatada entre mirabegrom e drogas antimuscarínicos para eficácia. A adesão ao tratamento foi de 87,7% em ambos os grupos [RR: 0,99 (0,98–1,00)]. CONCLUSãO:  Mirabegrom e antimuscarínicos têm eficácia e taxas de adesão comparáveis, porém o mirabegrom apresentou menos eventos adversos totais e isolados.

Topics: Acetanilides; Cholinergic Antagonists; Female; Humans; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Overactive

Systematic review.. To evaluate the efficacy and safety of mirabegron in patients with neurogenic detrusor overactivity due to SCI or MS.. A comprehensive search of the Pubmed, Cochrane, Scopus, and Embase databases was performed. Studies evaluating adult patients with neurogenic detrusor overactivity due to SCI or MS were analyzed according to clinical and urodynamic outcome parameters.. A total of 488 patients were included in 11 studies, with sample sizes ranging from 15 to 91. The duration of the treatments varied from 4 weeks to 12 months. Mirabegron was used as a secondline treatment after anticholinergics in most of the studies. While clinical outcome parameters are used in studies involving only MS patients, urodynamic outcome parameters are also used in studies involving patients with SCI. The efficacy of mirabegron was found not to be different than anticholinergics when compared in MS patients. Comprehensive urodynamic evaluation was performed in 2 randomized, double-blind, placebo-controlled studies and no satisfactory results were obtained compared to placebo. In retrospective studies there were some significant improvements in P. Although mirabegron demonstrates similar clinical efficacy to anticholinergics in MS patients, its effect on urodynamic parameters in patients with SCI cannot be considered satisfactory. It has a good safety profile with mild cardiovascular side effects.

Topics: Acetanilides; Adult; Cholinergic Antagonists; Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic; Retrospective Studies; Spinal Cord Injuries; Thiazoles; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

Overactive bladder (OAB) is defined as urinary urgency, usually with urinary frequency and nocturia. . The current treatment for OAB includes conservative management, surgery, and pharmacotherapy. Mirabegron is a new drug acting by the ß3-adrenoceptor agonism. This study aimed to review the cost-effectiveness of mirabegron in the treatment of OAB.. We searched published articles in electronic search databases. Ten studies were included in the qualitative analysis. Various antimuscarinics, including oxybutynin, fesoterodine, tolterodine, darifenacin, and trospium were compared with mirabegron. The results were evaluated and compared according to the quality-adjusted life-years (QALY), cost/year, and incremental cost-effectiveness ratio (ICER). Of the ten studies in only three, mirabegron was not a cost-effective strategy. In seven cases, mirabegron was cost-effective.. The cost-effectiveness of mirabegron was variable in different regions; however, most of the studies show the cost-effectiveness of mirabegron. Our study illustrates that mirabegron's ICER in comparison with its comparators is below the willingness to pay threshold even in the countries with low GDP/Capita. Our proposal for future economic studies for OAB pharmacotherapy is to compare different doses, formulations, and administration forms in a real-world context.

Topics: Acetanilides; Cost-Benefit Analysis; Humans; Muscarinic Antagonists; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder (OAB) symptoms of frequency, urgency and urge incontinence are frequently associated with known neurological diseases like multiple sclerosis (MS), spinal cord injury (SCI), Parkinson's disease (PD), stroke.. The aim of our study was to review the efficacy of pharmacological and non-pharmacological treatments for neurogenic overactive bladder.. We searched two electronic databases (PubMed and EMBASE) for randomized controlled trials focusing on pharmacological and non-pharmacological medical treatments for overactive bladder symptoms associated with neurological diseases published up to 30 April 2022.. A total of 157 articles were retrieved; 94 were selected by title and abstract screening; after removal of 17 duplicates, 77 records were evaluated by full-text examination. Sixty-two studies were finally selected. The articles selected for review focused on the following interventions: anticholinergics (n = 9), mirabegron (n = 5), comparison of different drugs (n = 3), cannabinoids (n = 2), intravesical instillations (n = 3), botulinum toxin (n = 16), transcutaneous tibial nerve stimulation (TTNS) (n = 6), acupuncture (n = 2), transcutaneous electrical nerve stimulation TENS (n = 4), pelvic floor muscle training (PFMT) (n = 10), others (n = 2). Anticholinergics were more effective than placebo in decreasing the number of daily voids in patients with PD (mean difference [MD]- 1.16, 95 % CI - 1.80 to - 0.52, 2 trials, 86 patients, p < 0.004), but no significant difference from baseline was found for incontinence episodes and nocturia. Mirabegron was more effective than placebo in increasing the cystometric capacity in patients with MS (mean difference [MD] 89.89 mL, 95 % CI 29.76 to 150.01, 2 trials, 98 patients, p < 0.003) but no significant difference was observed for symptom scores and bladder diary parameters. TTNS was more effective than its sham-control in decreasing the number of nocturia episodes (MD -1.40, 95 % CI -2.39 to -0.42, 2 trials, 53 patients, p < 0.005) but no significant changes of OAB symptom scores were reported. PFMT was more effective than conservative advice in decreasing the ICIQ symptom score (MD, -1.12, 95 % CI -2.13 to -0.11, 2 trials, 91 patients, p = 0.03), although the number of incontinence episodes was not significantly different between groups.. The results of the meta-analysis demonstrate a moderate efficacy of all considered treatments without proving the superiority of one therapy over the others. Combination treatment using different pharmacological and non-pharmacological therapies could achieve the best clinical efficacy due to the favorable combination of the different mechanisms of action. This could be associated with fewer side effects due to drug dosage reduction. These data are only provisional and should be considered with caution, due to the few studies included in metaanalysis and to the small number of patients.

Topics: Cholinergic Antagonists; Humans; Nocturia; Pelvic Floor; Randomized Controlled Trials as Topic; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence

In the absence of head-to-head trials, we performed an indirect treatment comparison of the β. PubMed, Embase, and Cochrane Library were searched for articles related to phase 3, double-blind, controlled trials of vibegron 75 mg and mirabegron 25/50 mg in patients with OAB. Efficacy outcomes included change from baseline at weeks 4, 12, and 52 in mean daily number of total urinary incontinence episodes and micturitions and mean volume voided/micturition. Effect size was computed as placebo-subtracted change from baseline (weeks 4, 12) or active control (tolterodine)-subtracted change from baseline (week 52) for each treatment group. Adverse events (AEs) are presented descriptively.. After removal of duplicates, 49 records were identified, and after screening 9 met inclusion criteria for analysis. Vibegron showed significantly greater reduction in mean daily number of total incontinence episodes than mirabegron 25 mg at week 4, mirabegron 50 mg (weeks 4, 52), and tolterodine (weeks 4, 12) (P < 0.05, each) and significantly greater improvement in volume voided versus mirabegron 25 mg (week 12), mirabegron 50 mg (weeks 12, 52), and tolterodine (week 4) (P < 0.05, each). Confidence intervals of point estimates overlapped zero for all other comparisons of vibegron and mirabegron (25 or 50 mg) or tolterodine, indicating no significant differences between treatments for these time/endpoints. Urinary tract infection, hypertension, and dry mouth were the most commonly occurring AEs for vibegron, mirabegron, and tolterodine, respectively, in the short-term trials; hypertension was the most commonly occurring AE with all three treatments in the long-term trials.. Vibegron was associated with significant improvement in total incontinence episodes versus mirabegron at 4 and 52 weeks and volume voided at 12 and 52 weeks. Improvement in micturitions was similar between vibegron and mirabegron or tolterodine. Incidence of AEs was generally comparable between vibegron and mirabegron.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Clinical Trials, Phase III as Topic; Double-Blind Method; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

We conducted this meta-analysis to explore the tolerance of monotherapy with mirabegron (50 mg) on an overactive bladder, compared with a common dosage of anticholinergic agents.. A comprehensive search for all randomized controlled trials that evaluated the safety of mirabegron and anticholinergic agents on overactive bladder was performed, and we searched the Cochrane Central Register of Controlled trials databases, Pubmed, Embase, and relevant trials from 2013.02 to 2019.10.. Eight studies included 5500 patients with treatment of monotherapy on overactive bladder were identified. The total number of treatment-emergent adverse events had no significantly difference between two monotherapies (RR = 0.88 95%CI: 0.76-1.01; P = .08); however, patients would have a better tolerance with mirabegron (50 mg) in adverse events of dry mouth (RR = 0.42; 95%CI: 0.33-0.53; P < .01) and tachycardia (RR = 0.52; 95%CI: 0.29-0.94; P = .03); and there were no significant differences between two groups in hypertension (RR = 1.02; 95%CI: 0.80-1.30; P = .90), constipation (RR = 0.91; 95%CI: 0.65-1.26; P = 0.57), blurred vision (RR = 1.03; 95%CI: 0.60-1.77; P = 0.92), and urinary tract infection (RR = 0.90; 95%CI: 0.70-1.16; P = .41).. Treatment-emergent adverse events in patients with overactive bladder who underwent monotherapy of mirabegron (50 mg) or the anticholinergic agents had no significant differences, but mirabegron has a better tolerance in the aspect of dry mouth and tachycardia.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cholinergic Antagonists; Constipation; Female; Humans; Hypertension; Male; Middle Aged; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Safety; Tachycardia; Thiazoles; Urinary Bladder, Overactive; Urinary Tract Infections; Vision, Low; Xerostomia

Vibegron is a very selective new β3-adrenergic receptor agonist introduced recently to clinical practice for OAB patients, which offers an alternative option for to antimuscarinic drugs.. This review presents the current knowledge concerning the mechanism of action, pharmacokinetics, and pharmacodynamics of vibegron. Moreover, it presents an overview of preclinical and phase II and phase III clinical studies on the efficacy, tolerability, and safety of this agent in patients suffering from OAB.. Clinical studies confirmed efficacy and safety of vibegron in OAB patients. Vibegron differ from well-known mirabegron with regards to its pharmacological profile because it is metabolized independently from CYP3A4, 2D6, or 2C9 and therefore is less likely to cause a drug-drug interaction. Moreover, since this drug does not penetrate the blood-brain barrier, it could become the drug of choice in OAB patients with cognitive impairment. These properties have paved the way in near future for better-tailored treatments for OAB patients.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

To review the efficacy and safety of mirabegron in men with overactive bladder (OAB) and benign prostatic hyperplasia (BPH).. Numerous studies have shown mirabegron to be efficacious and safe in treating symptoms of OAB. More recent studies evaluating the use of mirabegron in men with OAB and BPH have also shown the medication to be effective with few adverse side effects when used as monotherapy or in combination therapy. Mirabegron is an effective and safe treatment for men with OAB and BPH.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Humans; Lower Urinary Tract Symptoms; Male; Prostatic Hyperplasia; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Mirabegron (MYRBETRIQ

Topics: Acetanilides; Administration, Oral; Adolescent; Adrenergic beta-3 Receptor Agonists; Child; Child, Preschool; Clinical Trials, Phase III as Topic; Drug Approval; Female; Humans; Male; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

The safety of mirabegron 50mg monotherapy was comprehensively assessed versus placebo for overactive bladder.. A systematic literature search was conducted up to June, 2020 using PUBMED, EMBASE and Cochrane Library. Randomized controlled trials evaluating safety of mirabegron in overactive bladder were collected, and safety was assessed according to 15 adverse events. Adverse events were widely selected to be assessed if they could be calculated. Heterogeneity among studies was assessed by using the χ. In all, 10 peer-reviewed trials comprising 6135 patients were identified. Compared with placebo, mirabegron 50mg had an unfavorable safety profile resulting in nasopharyngitis (OR, 1.54[95% credible interval, 1.05-2.25]; P=0.03. No statistical difference was found between mirabegron 50mg and placebo groups in other 14 outcomes.. Mirabegron 50mg is further confirmed to be nearly as safe as placebo, expect for nasopharyngitis. Nasopharyngitis is associated with mirabegron 50mg monotherapy for patients with overactive bladder.

Topics: Acetanilides; Humans; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Mirabegron has promising results for OAB symptoms in adults, although the potential for cardiovascular side effects has caused concern. Efficacy and tolerability in children have not been extensively studied. Effectiveness, tolerability, and side effects of Mirabegron are reported in children with refractory OAB.. A retrospective review of children receiving Mirabegron between February 2014 and November 2018 was completed. Frequency, urgency, nocturnal (NE), and daytime incontinence (DI) were analyzed at baseline and 6 months.. 70 children (50 females), median age 15 [range 8-16] years, commenced Mirabegron 25 mg (n = 29) or 50 mg (n = 41). 37 (53%) were still receiving treatment at 6 months: monotherapy n = 30, and combination therapy n = 7 (Solifenacin n = 4, Desmopressin n = 2, both n = 1). Where undertaken, blood pressure monitoring and ECGs were normal. For patients on monotherapy, 6 of 17 (35%) had improvement in NE, 11 of 19 (58%) in DI, 12 of 20 (60%) in frequency, and 8 of 21 (38%) in urgency symptoms. For patients receiving combination therapy, 2 of 6 (33%) had improvement in NE, 2 of 4 in DI (50%), 2 of 4 (50%) in frequency, and 4 of 6 (67%) had improvement in urgency. Reasons for treatment discontinuation (entire cohort) were: ineffectiveness (n = 28), worse symptoms (n = 4) and/or adverse reactions (n = 7), including dry mouth (n = 2), headaches (n = 4), dizziness (n = 1), nausea/vomiting (n = 3), increased seizures (n = 1), and rash (n = 1).. Mirabegron improved symptoms in 70% of patients with refractory OAB. A prospective RCT should be the next step to establish the role of Mirabegron for the treatment of OAB in children.. Level II.

Topics: Acetanilides; Adolescent; Child; Female; Humans; Male; Pilot Projects; Retrospective Studies; Thiazoles; Urinary Bladder, Overactive; Urological Agents

We conducted a meta-analysis to assess the efficacy and safety of mirabegron on overactive bladder (OAB) induced by benign prostatic hyperplasia (BPH) in men receiving tamsulosin therapy.. We performed the analysis by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The databases including MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were retrieved to get information regarding randomized controlled trials of mirabegron on OAB induced by BPH in men receiving tamsulosin therapy. We also searched the references of included literatures.. Three randomized controlled trials containing a total of 1317 BPH patients were included in the analysis. Co-primary efficacy end points: the mean number of micturitions per day [the mean difference (MD) = -0.27, 95% confidence interval (CI): -0.46 to -0.09, P = .004], the urgency episodes per day (the MD = -0.50, 95% CI: -0.77 to -0.22, P = .0004), the total OAB symptom score (the MD = -0.69, 95% CI: -1.00 to -0.38, P < .0001), and mean volume voided (the MD = 10.76, 95% CI: 4.87-16.64, P = .0003) indicated that mirabegron was effective in treating OAB induced by BPH in men receiving tamsulosin therapy. Safety assessments that included treatment-emergent adverse events (odds ratio = 0.88, 95% CI: 0.68-1.13, P = .31) indicated that mirabegron was well tolerated with the exception of post-void residual urine volume (MD = 12.02, 95% CI: 6.01-18.04, P < .0001).. This analysis demonstrates that mirabegron is an effective and safe treatment for OAB symptoms induced by BPH in men receiving tamsulosin therapy with a low occurrence of side effects. Besides, we should be aware that the administration of mirabegron might have the risk of increasing post-void residual urine volume.

Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Humans; Male; Prostatic Hyperplasia; Randomized Controlled Trials as Topic; Tamsulosin; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

To determine whether electronic bladder diaries are associated with a larger placebo effect than paper diaries in studies of overactive bladder (OAB). To identify any other factors in study design that may influence the placebo effect.. This is a secondary analysis of a previous systematic review and network meta-analysis on the efficacy and tolerability of mirabegron. Each study was analysed and placebo response rate (PRR) was calculated. Statistical analysis was used to look for associations with different factors and PRR.. The PRR was considerable in the studies analysed (10.5 % when calculated for change in number of micturitions over 24 h and 41.2 % for change in urgency urinary incontinence episodes over 24 h). Paper bladder diaries were associated with a significantly larger placebo response rate than electronic (10.76 % vs 10.22 %), although this may be clinically small. The size of study had a moderate positive correlation with PRR. Length of bladder diary was not associated with increased PRR.. The PRR in studies of OAB is varied and significant. It is clear that it can be affected by factors in study design including type of bladder diary. When designing clinical studies this should be borne in mind. Equally, when attempting to optimise patient care, the benefit of the therapeutic encounter should be remembered.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Data Collection; Humans; Patient Reported Outcome Measures; Placebo Effect; Thiazoles; Urinary Bladder, Overactive

Overactive bladder syndrome is a broadly occurring urological disorder with a distressing impact on the quality of life. The commonly used antimuscarinic drugs show poor patient compliance because of unsatisfactory potency, tolerability and high occurrence of adverse effects such as dry mouth, blurred vision, constipation, dizziness etc. Mirabegron is the first approved β3-adrenoreceptor agonist, used as mono or in combination therapies for overactive bladder syndrome.. The present review provides an insight into the mechanism, pharmacokinetics, toxicokinetics, clinical trials and the development of various conventional and modified-release dosage forms of mirabegron for the treatment of overactive bladder syndrome.. The clinical trials of phase II and phase III of mirabegron demonstrated symptomatic relief from the overactive bladder without disturbing the micturition cycle. To date, mirabegron showed promising results for safety, tolerability and efficacy in patients with overactive bladder syndrome. The modified-release tablet dosage form of mirabegron appear to be a proficient and suitable replacement for antimuscarinics and revealed the tremendous potential to overcome the adverse effects of conventional antimuscarinic drugs like Oxybutyline chloride ER, Detrol LA, VESIcare, etc. Conclusion: Mirabegron shows a distinct mode of action, i.e., targeting β3-adrenoreceptors and improving bladder storage without altering void contractions. The limited side effects, high safety, efficacy and tolerability of mirabegron present an adequate substitute to antimuscarinics. However, long-term analysis and clinical studies are prerequisites for assessing the safety, tolerability and efficacy profile of mirabegron.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Delayed-Action Preparations; Humans; Randomized Controlled Trials as Topic; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Lower urinary tract symptoms, including urgency, urgency incontinence, frequency, and nocturia, are highly prevalent in older adults and are associated with significant morbidity and impairment in quality of life. When conservative measures such as bladder training fail to improve symptoms, pharmacological management is recommended by national and international guidelines. Mirabegron, an agonist of the β3 adrenergic receptor, demonstrates similar efficacy to the anticholinergic drugs without the risk of anticholinergic effects, but experience and evidence in the very elderly population are limited. This narrative review examines the current evidence base for mirabegron in very elderly adults.

Topics: Acetanilides; Age Factors; Aged; Aged, 80 and over; Female; Humans; Lower Urinary Tract Symptoms; Nocturia; Patient Safety; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

Mirabegron is a β3-agonist drug approved by the FDA for use in 2012 and administered in overactive bladder. Activating of adrenergic receptors leads to the relaxation of the detrusor muscle. According to the latest research and reports, it also has lipolytic activity, affecting the reduction of mainly brown adipose tissue (BAT) but also of white adipose tissue (WAT). This results in a decrease in body weight and triglyceride concentration and an increase in lipoprotein lipase activity, as well as in the level of free fatty acids or adipokines in the plasma. The drug indirectly participates in the regulation of carbohydrate metabolism, influencing the increase in insulin sensitivity, supporting cellular uptake of glucose. However, due to the elevation of blood pressure and pulse, as a supplement, the drug should be taken with care to avoid cardiovascular complications. In our review, below, we present a description and discussion of available studies in terms of mirabegron action on the exercise capacity of the body in the context of its potential use as a doping agent.

Topics: Acetanilides; Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Adrenergic beta-3 Receptor Agonists; Animals; Exercise Tolerance; Humans; Lipolysis; Thiazoles; Urinary Bladder, Overactive

Reviews assessing mirabegron's safety and efficacy, synthesize data from both genders, without providing specific details for female patients with OAB. The aim of this study is to qualitatively and quantitatively synthesize data evaluating mirabegron's use on female patients with OAB. PubMed/Scopus/Cochrane library/Web of Knowledge were searched for full texted, published in English-language and in peer-reviewed journals, up to November 2019, using the keyword "mirabegron".Jadad score modified by adding allocation concealment, MINORS and RoB were used for the Methodological quality and risk of bias assessment. Twenty-one studies were included in this review;7 RCTs, 3 non-RCTs and 11 observational studies. Controlled trials were of unclear (75%), high (12.5%) or serious risk (12.5%) of bias. Twelve weeks of mirabegron use resulted in significant decrease of urgency, frequency, nocturia and UUI by 1.3-2.2,2.04-2.33,0.42-0.5 and 0.9-1.04 episodes/24 h, respectively. Quality of life and sexual health was improved significantly. Sexual dysfunction decreased from 98% (84/85) at baseline, to 60% (51/85) after 12-weeks of mirabegron (p-value < 0.001). Mirabegron had the same efficacy as anticholinergics in improving all OAB symptoms but with fewer adverse events. Hypertension and antimuscarinics' effects (i.e dry mouth, constipation) had an incidence of 2% (28/1221) and 1.9% (23/1221) when mirabegron was administered, respectively. Mirabegron is a safe and effective alternative therapy for females with OAB. However, there is a paucity of high-quality RCTs, with large sample sizes, long-term follow-up focusing on mirabegron's comparison to other therapies, quality of life and sexual health of female patients with OAB.

Topics: Acetanilides; Female; Humans; Male; Muscarinic Antagonists; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Overactive bladder syndrome (OAB) is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology. The mainstay of treatment of OAB is anticholinergic/antimuscarinic medication. These drugs block muscarinic receptors throughout the body, not only the bladder, including in the brain, which may lead to cognitive side effects. Anticholinergic load or burden is the cumulative effect of taking drugs that are capable of producing anticholinergic adverse effects. The elderly are more susceptible to these effects, especially as there is increased permeability of the blood brain barrier. The anticholinergic drugs for OAB are able to enter the central nervous system and lead to central side effects. There is increasing evidence that a high anticholinergic load is linked to the development of cognitive impairment and even dementia. Some studies have found an increased risk of mortality. In view of this, care is needed when treating OAB in the elderly. Trospium chloride is a quaternary amine anticholinergic, which has a molecular structure, which theoretically means it is less likely to cross the blood brain barrier and exert central side effects. Alternatively, mirabegron can be used, which is a beta-3 adrenoceptor agonist, which does not add to the anticholinergic load or exert central nervous system side effects. Conservative therapy can be used as an alternative to pharmacological treatment in the form of behavioral modification, fluid management and bladder retraining. Neuromodulation or the use of botox can also be alternatives, but success may be less in the older adult and will require increased hospital attendances.

Topics: Acetanilides; Aged; Behavior Therapy; Benzilates; Blood-Brain Barrier; Cholinergic Antagonists; Cognitive Dysfunction; Female; Humans; Muscarinic Antagonists; Nortropanes; Thiazoles; Urinary Bladder, Overactive

Cumulative exposure to one or more anticholinergic medications ("anticholinergic burden") is associated with an increased risk of adverse outcomes, particularly among older individuals. Mirabegron, an oral selective β3-adrenergic receptor agonist, has demonstrated efficacy in managing the symptoms of overactive bladder without contributing to anticholinergic burden. However, it is not known whether the favorable safety profile of mirabegron relative to antimuscarinics varies with increasing age among a patient population who may have a high anticholinergic burden.. The primary objective of this study was to indirectly compare the safety and efficacy profile of mirabegron relative to antimuscarinics in older adults with overactive bladder.. A systematic literature review was conducted to identify randomized controlled trials that reported safety and efficacy endpoints among patients aged ≥ 65 years. Identified randomized controlled trials were subsequently synthesized via a network meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines in designing, performing, and reporting the literature review were followed. In line with current best practices, the network meta-analysis was conducted using a Bayesian approach and according to the overall general guidance for evidence synthesis developed by the National Institute for Health and Care Excellence decision support unit. Estimates of relative safety were assessed via the odds ratio and estimates of relative efficacy were assessed via means and credible intervals.. A total of 3078 abstracts, 300 of which underwent full-text screening, were identified using the search criteria. Twenty articles reporting on 21 randomized controlled trials were eligible for data extraction and synthesis. Following review, five safety and five efficacy endpoints were considered for inclusion in the network meta-analysis. Regarding findings typical of anticholinergic exposure in older adults, mirabegron was not associated with an increased odds of dry mouth (odds ratio 95% credible interval 0.76 [0.26-2.37]) or constipation (1.08 [0.39-3.02]) relative to placebo, whereas antimuscarinics were strongly associated with these events (odds ratio range 3.78-7.85 and 2.12-4.66, respectively). In this older population, mirabegron was associated with a similar odds of experiencing adverse event-related treatment discontinuations relative to placebo (0.99 [0.57-1.70]), while the odds of experiencing an adverse event-related treatment discontinuation for antimuscarinics had a range of 1.14-3.03 (in most cases, the association was mild). No increased odds of experiencing overall treatment-emergent adverse events was observed for mirabegron or antimuscarinics (odds ratio range 1.25-1.55), apart from fesoterodine (2.23 [1.37-3.37]). Finally, a similar treatment effect was observed across all efficacy endpoints between mirabegron and antimuscarinics in this older population.. This study indicates that the safety and efficacy profile of mirabegron remains favorable compared with antimuscarinics among older adults. This includes safety outcomes typically associated with anticholinergic burden, which were less frequently observed in patients treated with mirabegron.

Topics: Acetanilides; Aged; Benzhydryl Compounds; Constipation; Female; Humans; Male; Muscarinic Antagonists; Network Meta-Analysis; Odds Ratio; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder syndrome (OAB) is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology. In this review, we focus on recent advances in the management of OAB. We examine the evidence on the effect of anticholinergic load on OAB patients. Advances in medical treatment include a new beta-3 agonist, vibegron, which is thought to have fewer drug interactions than mirabegron. Treatment of genitourinary syndrome of the menopause with oestrogens and ospemifene have also shown promise for OAB. Botulinum toxin has been shown to be an effective treatment option. We discuss the new implantable neuromodulators that are on the market as well as selective bladder denervation and laser technology.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Botulinum Toxins; Denervation; Drug Implants; Humans; Laser Therapy; Pyrimidinones; Pyrrolidines; Tamoxifen; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

This paper discusses the recent evidence supporting beta 3 adrenergic agonists as the preferred pharmacological management of overactive bladder syndrome.. Mirabegron has a similar efficacy profile to first-line antimuscarinics with favorable adverse effects profile. Treatment of OAB with beta-3 adrenergic agonist should be favored in patients at higher risk of anticholinergic adverse events. The efficacy and tolerability of beta-3 adrenergic agonists are consistently reported in older OAB patients, whether used alone or with other antimuscarinics. Mirabegron is cost-effective in treating OAB unless the symptoms were severe or refractory. Combination therapy of mirabegron and other pharmacotherapy has proven to be efficient in controlling OAB symptoms without inducing serious add-on adverse effects. While beta-3 adrenergic agonists bear favorable advantages in OAB treatment, physicians should perform a thorough and careful pre-treatment planning to optimize treatment benefits and adherence.

Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Cholinergic Antagonists; Cost-Benefit Analysis; Humans; Muscarinic Antagonists; Phosphodiesterase Inhibitors; Pyrimidinones; Pyrrolidines; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Overactive bladder syndrome (OAB) is a prevalent disorder with a significant impact on quality of life. Despite this high prevalence, there is significant underdiagnosis and undertreatment due to several barriers, including embarrassment, poor communication and low patient adherence. Currently, various antimuscarinic are available in the treatment of OAB. The introduction of mirabegron has broadened the therapeutic approach and combination therapy of both agents can be valuable in clinical practice. Yet, patient adherence to most drugs for OAB is still relatively poor. Healthcare providers need to identify and utilise strategies to improve treatment adherence by defining clear treatment goals, implement educational methods and frequently communicate with patients to identify problems with adherence. The elderly population form need special attention as in these patients, anticholinergics should be prescribed with care and adequate knowledge regarding pharmacokinetics and drug interactions in essential. Furthermore, patient expectations should be clearly discussed. In this narrative review, the current advances in oral pharmacotherapy are evaluated and the most important factors involved in the management of OAB are discussed.

Topics: Acetanilides; Administration, Oral; Adrenergic beta-3 Receptor Agonists; Aged; Case-Control Studies; Cholinergic Antagonists; Drug Therapy, Combination; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Patient Compliance; Prevalence; Quality of Life; Thiazoles; Urinary Bladder, Overactive

We conducted a meta-analysis to evaluate the safety and efficacy of mirabegron (50 mg) and solifenacin (5 mg) monotherapy for overactive bladder (OAB) during a 12-week cycle.. Randomized controlled trials (RCTs) of mirabegron and solifenacin for OAB were searched systematically by using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of retrieved studies were also perused.. Five RCTs which compared solifenacin with mirabegron were studied. Mirabegron achieved the same effect as solifenacin in treating OAB. The mean number of incontinence episodes per 24 h (P = 0.20), mean number of micturitions per 24 h (P = 0.11), mean number of urgency episodes per 24 h (P = 0.23), and mean volume voided per micturition (P = 0.05) suggested that mirabegron and solifenacin had no significant differences in terms of OAB treatment. With regard to drug-related treatment-emergent adverse events (DR-TEAEs) and dry mouth, mirabegron showed better tolerance than solifenacin. Post-voiding residual volume showed a distinct difference in the two groups. Hypertension and tachycardia did not show a significant difference between the two groups, but the pulse rate did.. The therapeutic effect of mirabegron is similar to that of solifenacin, and mirabegron does not increase the risk of adverse events (AEs).

Topics: Acetanilides; Humans; Randomized Controlled Trials as Topic; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive; Urological Agents

The objective was to identify the most commonly used patient-reported outcome (PRO) instruments for overactive bladder (OAB), determine which are the most useful for measuring burden in OAB and characterize the findings of recent studies that have employed PRO instruments to assess OAB symptoms and the effects of treatment.. A systematic search of OAB literature published between January 2006 and November 2017 using Medline/PubMed and EMBASE databases.. Of 3425 abstracts and 500 full-text articles reviewed, 58 studies (both clinical trials and observational studies) were included in the review. The most commonly used PRO instruments were the OAB Questionnaire (OAB-q; 64%), followed by the King's Health Questionnaire (KHQ; 31%) and the Patient Perception of Bladder Condition (PCBC; 21%). Synthesis of data from studies using the OAB-q showed that OAB treatment with antimuscarinics, mirabegron and onabotulinumtoxinA all improve health-related quality of life (HRQoL) and symptoms beyond the benefits observed with placebo. The OAB-q could detect dose-response relationships in some studies and demonstrated there were no significant differences across therapies from different drug classes.. The HRQoL burden of OAB and response to treatment can be reliably measured by PRO instruments, and the OAB-q is the most commonly used instrument in OAB, particularly in clinical trials of OAB interventions. These data will be useful to provide benchmarks of burden levels for PRO scores obtained among those on contemporary therapies for comparison with outcomes from patients managed with emerging treatments.. Astellas Pharma Global Development, Inc.

Topics: Acetanilides; Botulinum Toxins, Type A; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Reported Outcome Measures; Quality of Life; Surveys and Questionnaires; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To compare the efficacy and safety of mirabegron and onabotulinumtoxinA in the management of treatment-experienced patients with overactive bladder.. The network meta-analysis was based on evidence from a systematic literature review of randomized controlled trials and a post-hoc analysis of treatment-experienced subpopulations from mirabegron studies.. Nineteen trials described in 21 publications were included.. Overall, compared to mirabegron, there was some evidence that onabotulinumtoxinA was associated with improved outcomes, including reductions in the number of micturitions in a 24-hour period, and the number of incontinence episodes. However, mirabegron was associated with a lower risk of urinary tract infections compared with onabotulinumtoxinA.

Topics: Acetanilides; Administration, Oral; Adrenergic beta-3 Receptor Antagonists; Aged; Aged, 80 and over; Bayes Theorem; Botulinum Toxins, Type A; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Muscarinic Antagonists; Network Meta-Analysis; Prognosis; Randomized Controlled Trials as Topic; Retreatment; Thiazoles; Treatment Failure; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics

A systematic review and meta-analysis was carried out to evaluate the efficacy and safety of mirabegron 50 mg and 100 mg in the treatment of storage lower urinary tract symptoms/overactive bladder in comparison with a placebo and tolterodine 4 mg. A total of 491 articles were collected and eight randomized studies were identified as eligible for this meta-analysis. Overall, eight trials were included in the meta-analysis evaluating 10 248 patients. Mirabegron at both doses of 50 mg and 100 mg, and and tolterodine 4 mg were significantly associated with the reduction of incontinence episodes per 24 h, reduction of mean number of micturitions per 24 h, increase of voided volume and reduction of urgency episodes per 24 h, compared to a placebo. Both mirabegron 50 mg and mirabegron 100 mg were associated with a significant reduction of nocturia episodes when compared with a placebo. Conversely, tolterodine 4 mg did not prove to be more effective than a placebo in the reduction of nocturia episodes. Furthermore, mirabegron 50 mg showed a slightly, but significantly, better efficacy than tolterodine 4 mg in the improvement of nocturia episodes. Mirabegron 50 mg and mirabegron 100 mg shared the same risk of overall treatment-emergent adverse events rate with the placebo. Otherwise, tolterodine 4 mg was associated with a significantly greater risk than the placebo. However, mirabegron 100 mg showed a slight trend toward an increased risk of hypertension (odds ratio 1.41; P = 0.08) and cardiac arrhythmia (odds ratio 2.18; P = 0.06). Mirabegron is an effective treatment for patients with storage lower urinary tract symptoms/overactive bladder, providing a reduction of incontinence, urgency and frequency; an improvement of voided volume with a slight, but statistically, significant improvement of nocturia; with a good safety profile. These findings should be considered for the treatment planning of patients with storage lower urinary tract symptoms/overactive bladder.

Topics: Acetanilides; Humans; Lower Urinary Tract Symptoms; Nocturia; Randomized Controlled Trials as Topic; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Overactive bladder (OAB) syndrome is common in the general population, particularly in elderly patients. Antimuscarinic drugs (AMs) are considered the mainstay pharmaceutical treatment of OAB whereas β3-adrenoceptor agonists, such as mirabegron, represent a good alternative. Owing to the important role of muscarinic and β3 receptors in cardiovascular (CV) tissue and to the fact that OAB patients often have CV comorbidities, the safety-profile of these drugs constitute an important challenge.. The aim of this review is to evaluate the CV effects of AMs and mirabegron in OAB. A systematic literature search from inception until December 2017 was performed on PubMed and Medline.. AMs are generally considered to have good CV safety profile but, however, they may cause undesirable adverse events, such as dry mouth, constipation. CV AEs are rare but noteworthy, the most common CV consequences related to the use of these drugs are constituted by an increase in HR and QT interval. Mirabegron has similar efficacy and tolerability to AMs but causes less adverse events, with either modest hypertension and modest increase in HR (<5 bpm) being the most commonly reported.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Cardiovascular Diseases; Heart Rate; Humans; Hypertension; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive

Mirabegron, a β3-adrenoceptor agonist, was approved for overactive bladder (OAB), but worsened hypertension was a potential risk based on its mechanism of action. Besides, head to head comparisons were limited between mirabegron and antimuscarinic agents, the prior first-line pharmacotherapy of OAB. In this regard, we performed a systematic review and meta-analysis to compare their efficacy as well as safety, especially in blood pressure changes.. Literature search was conducted in PubMed, Medline and seven randomized clinical trial (RCT) register databases of WHO, EU, USA, Taiwan, China, Japan and Cochrane. Completed RCTs for OAB with mirabegron and antimuscarinics were identified and the last comprehensive search was run in August 2017. Cochrane risk of bias tool was used to assess the potential bias, and RevMan5 software was performed for meta-analysis.. Seven eligible RCTs (four for mirabegron vs. tolterodine and three for mirabegron vs. solifenacin) were included and demonstrated similar efficacy in micturitions, incontinence, and nocturia between mirabegron and antimuscarinics. In hypertension issue, no statistical differences were showed in risk ratio (RR) of hypertension events, change of blood pressure from baseline and change of blood pressure from placebo for all participants. On the other hand, RR of dry mouth was significantly lower in mirabegron users.. Mirabegron was not inferior effective in improving OAB symptoms compared with antimuscarinic agents. In addition, mirabegron presented lower incidence of dry mouth and not higher risk for hypertension. Therefore, mirabegron has potential to be an alternative therapeutic option for OAB control.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Female; Humans; Hypertension; Male; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive; Urological Agents

Mirabegron is an established treatment alternative to antimuscarinic therapy for patients with overactive bladder (OAB), as shown by efficacy and tolerability data from phase III trials.. To assess efficacy and tolerability of mirabegron 50mg versus antimuscarinic monotherapies and combination therapies.. Systematic literature review and network meta-analysis of randomised controlled trials (2000-2017) assessing eligible treatments for OAB.. Efficacy assessments included micturition frequency, urgency urinary incontinence, dry rate, and 50% reduction in incontinence. Tolerability assessments included dry mouth, constipation, blurred vision, and hypertension.. A total of 64 studies (n=46 666) were included in the network meta-analysis. Mirabegron 50mg was significantly more efficacious than placebo for all efficacy endpoints. Comparable overall efficacy was observed for mirabegron 50mg versus most active treatments, but solifenacin 10mg monotherapy and solifenacin 5mg plus mirabegron 25 or 50mg in combination were more efficacious for some/all outcomes. Mirabegron 50mg was significantly better tolerated regarding dry mouth, constipation, and urinary retention than 21/22, 9/20, and 7/10 active comparators, respectively; similar overall tolerability was observed between mirabegron 50mg and all treatments (including placebo) for the remaining endpoints. Limitations of the study included between-trial variations in the definition of certain endpoints and heterogeneity of the available data (eg, number of studies and patients assessed) for comparator treatments across different endpoints.. The relief of key OAB symptoms produced by mirabegron 50mg is significantly better than placebo, and similar to a range of common antimuscarinics, with the benefit of significantly fewer bothersome anticholinergic side effects such as dry mouth. Combination treatment of solifenacin 5mg plus mirabegron 25 or 50mg appears to provide an efficacy benefit compared with mirabegron 50mg, with the expected side effects of individual antimuscarinics.. This study assessed the efficacy and tolerability of different drug treatments for OAB. Mirabegron 50mg was as effective as antimuscarinic therapy, with fewer common, bothersome side effects such as dry mouth, constipation, and urinary retention. Combination treatment of solifenacin 5mg plus mirabegron 25 or 50mg was more effective than mirabegron 50mg alone, but with more anticholinergic side effects.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Recovery of Function; Thiazoles; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics; Urological Agents

The first-in-class β

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Female; Humans; Male; Muscarinic Antagonists; Signal Transduction; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

To evaluate persistence and adherence of oral pharmacotherapy used in the treatment of overactive bladder (OAB) in a real-world setting.. Systematic literature searches of six electronic publication databases were performed to identify observational studies of patients with OAB treated with antimuscarinics and/or mirabegron. Studies obtaining persistence and adherence data from sources other than electronic prescription claims were excluded. Reference lists of identified studies and relevant systematic reviews were assessed to identify additional relevant studies.. The search identified 3897 studies, of which 30 were included. Overall, persistence ranged from 5% to 47%. In studies reporting data for antimuscarinics and mirabegron (n=3), 1-year persistence was 12%-25% and 32%-38%, respectively. Median time to discontinuation was <5 months for antimuscarinics (except one study (6.5 months)) and 5.6-7.4 months for mirabegron. The proportion of patients adherent at 1 year varied between 15% and 44%. In studies reporting adherence for antimuscarinics and mirabegron, adherence was higher with mirabegron (mean medication possession ratio (MPR): 0.59 vs 0.41-0.53; mean proportion of days covered: 0.66 vs 0.55; and median MPR: 0.65 vs 0.19-0.49). Reported determinants of persistence and adherence included female (sex), older age group, use of extended-release formulation and treatment experience.. Most patients with OAB discontinued oral OAB pharmacotherapy and were non-adherent 1 year after treatment initiation. In general, mirabegron was associated with greater persistence and adherence compared with antimuscarinics. Combined with existing clinical trial evidence, this real-world review merits consideration of mirabegron for first-line pharmacological treatment among patients with OAB.. CRD42017059894.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Medication Adherence; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive

To evaluate the costeffectivenessof mirabegron in comparison to theantimuscarinic drugs tolterodine, solifenacin andfesoterodine, in the treatment of urgency, increasedmicturition frequency and urinary incontinence in patientswith overactive bladder (OAB).. A Markov model in Excel,with a time horizon of 5 years was developed fromthe National Health System and societal perspective.Clinical effectiveness was estimated from a clinical trial(SCORPIO) and a network meta-analysis. Unit costswere obtained from Spanish sources. The effectivenessof the treatments was measured as quality adjusted lifeyears(QALY). Deterministic and probabilistic sensitivityanalyses were performed.. For the 5-year time horizon, the incrementalcost per patient with mirabegron 50 mg versustolterodine was € 195.52 and € 157.42, from theNational Health System (NHS) and societal perspectivesrespectively, with a gain of 0.0127 QALY withmirabegron. Consequently, the cost of gaining a QALYwith mirabegron versus tolterodine was 15,432 € and12,425 € respectively. The probability that mirabegronwould be cost-effective at a willingness to pay thresholdof € 30,000 was: 70% (NHS) and 71% (society)versus tolterodine; 94% (NHS and society) versussolifenacin 5 mg; 84% (NHS) and 84.5% (society)versus solifenacin 10 mg; 96% (NHS and society)versus fesoterodine 4 mg; 98% (NHS) and 99% (society)versus fesoterodine 8 mg. The highest probability thatmirabegron would be cost-effective at a willingness topay threshold of € 20.000 and € 25.000 per QALYgained, is obtained versus fesoterodine 4 mg and 8 mgfrom both NHS and society perspectives.. The treatment of patients with OABwith mirabegron 50 mg is likely to be cost-effectivecompared to treatment with antimuscarinics.. Evaluar el coste-efectividad de mirabegrón frente a los fármacos antimuscarínicos tolterodina, solifenacina y fesoterodina, en el tratamiento sintomático de la urgencia, el aumento de la frecuencia miccional y la incontinencia de urgencia en los pacientescon vejiga hiperactiva (VH).MÉTODOS: Modelo de Markov en Excel, con un horizonte temporal de 5 años, desde la perspectiva del Sistema Nacional de Salud y de la sociedad. La efectividad clínica se obtuvo de un ensayo clínico frente a tolterodina y de un metaanálisis. Los costes unitarios se obtuvieron de fuentes españolas. La efectividad de los tratamientos se midió como años de vida ajustados por calidad de vida (AVAC). Se realizaron análisis de sensibilidad determinísticos y probabilísticos.. Para el horizonte temporal de 5 años, el coste incremental por paciente con mirabegrón 50 mg frente a tolterodina es de 195,52 € y 157,42 €, desde las perspectivas del Sistema Nacional de Salud (SNS) y social, respectivamente, con una ganancia de 0,0127 AVAC con mirabegrón. El coste de ganar un AVAC con mirabegrón frente a tolterodina sería de 15.432 € y de 12.425 €, respectivamente. La probabilidad de que mirabegrón sea coste-efectivo frente a tolterodina, sería del 70% y del 71%, respectivamente. Para el SNS, la probabilidad de coste-efectividad de mirabegrón frente a solifenacina 5 y 10 mg sería del 84% y del 84,5%, respectivamente y en comparación con fesoterodina 4 y 8 mg sería del 96% y 98%, respectivamente. CONCLUSIONES: El tratamiento de los pacientes con VH con mirabegrón 50 mg es probablemente coste- efectivo en comparación con el tratamiento con antimuscarínicos.

Topics: Acetanilides; Cost-Benefit Analysis; Humans; Muscarinic Antagonists; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

The prevalence rate of overactive bladder symptoms is 16% for men and 16.9% for women. Currently, m-anticholinergics are the first line of therapy. The selective and non-selective antimuscarinic drugs are available in Russian Federation. Some patients refuse long-term use of -anticholinergics due to either side effects, or insufficient efficacy. This situation prompted world scientific community to search of alternative treatment methods. Mirabegron is a selective 3-adrenoreceptors agonist, which represent a new approach to the treatment of patients with overactive bladder. In this article the studying of adrenoreceptors, properties of mirabegron and the possibilities for its applications are reviewed.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Russia; Thiazoles; Urinary Bladder, Overactive

The sympathetic nervous system is one component of the nervous regulatory system of the physiological function of the lower genitourinary tract. Our knowledge on the role of this sympathetic system has advanced during the last decade due to the characterization of β3-adrenoceptors (β3-ARs) in the urogenital system. This review focuses on the pharmacological and molecular evidence supporting the functional roles of β3-AR in male genitourinary tissues of various species. An electronic search in two different databases was performed including MEDLINE (PubMed) and EMBASE from 2010 to 2016. β3-agonists may be a promising alternative to antimuscarinics in the treatment of overactive bladder (OAB) based on available evidence. Although more recent studies have evaluated the involvement of β3-ARs in the physiological control and regulation of various tissues of the lower genitourinary tract mainly urinary bladder, penis, urethra, ureter, there are few innovations in the pipe-line. Among the β3-agonists, mirabegron is a unique drug licensed for the treatment of patients with OAB. Many drugs classified as β3-agonists are still under investigations for the treatment of OAB, lower urinary tract symptoms, ureteral stones, benign prostate hyperplasia, prostate cancer and erectile dysfunction. This review discusses the potential roles of β3-AR as new therapeutic targets by evaluating the results of preclinical and clinical studies related to male lower genitourinary tract function. Looking into the future, the potential benefits of β3- AR agonists from experimental and clinical investigations may provide an attractive therapeutic option.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Humans; Lower Urinary Tract Symptoms; Male; Male Urogenital Diseases; Muscarinic Antagonists; Receptors, Adrenergic, beta-3; Thiazoles; Urinary Bladder, Overactive

Overactive bladder (OAB) is a common and bothersome condition manifested by urgency, frequent urination, significantly impairing patients quality of life. The article presents an overview of the evidence on pharmacotherapy of neurogenic and idiopathic OAB. Selective M3 receptor blockers have been shown to be the medications of choice in treating these patients. Many studies have shown that solifenacin 10 mg is a starting dose for patients with OAB. Mirabegron (Betmiga) is the only 3-adrenergic receptor agonist approved for primary treatment of OAB patients refractory to anticholinergics or have their side effects. It seems promising to use this drug, both as monotherapy and concurrently with anticholinergic agents to improve treatment results in patients with idiopathic and neurogenic OAB.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Drug Combinations; Humans; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Solifenacin Succinate; Sulfonamides; Tamsulosin; Thiazoles; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive

Overactive bladder syndrome is a condition with high prevalence, which has a negative impact on patients' quality of life. A drug with a novel mechanism of action has been recently approved: mirabegron. The objective of this study is to review the scientific evidence available on mirabegron, with the aim to analyze its efficacy, safety and cost, and thus estimate its role within current pharmacotherapy. Methods: The effectiveness and safety of mirabegron were analyzed through an evaluation of scientific evidence. The cost of different pharmacological alternatives was calculated based on their Defined Daily Dose (DDD) and their manufacturer's sale price. Results: The use of mirabegron in the treatment of overactive bladder syndrome is supported by three randomized clinical trials, controlled with placebo, at 12 weeks. All three share the same primary efficacy variables (number of incontinence episodes per 24 hours and number of micturitions per 24 hours). Long-term efficacy data are based on a 12-month study, where efficacy outcomes were measured as secondary variables. In all studies, mirabegron showed a significant but modest effect. Some of the most frequently detected adverse effects were: hypertension, increase of glucose in blood, headache, urinary tract infections, constipation and tachycardia. Special attention must be paid to cardiovascular events. Conclusions: The clinical efficacy of mirabegron is very modest and comparable to that achieved with the other drugs approved for this indication. Moreover, it is more expensive than other therapeutic options. Cardiac risks and urinary infections only allow to consider it as an alternative option to anticholinergic drugs, when these are contraindicated, show no clinical efficacy, or cause unacceptable adverse effects.. Objetivo: El síndrome de vejiga hiperactiva es una patología con elevada prevalencia y que tiene un impacto negativo sobre la calidad de vida de los pacientes. Recientemente se ha aprobado un fármaco con un novedoso mecanismo de acción: el mirabegrón. El objetivo de este estudio es revisar la evidencia científica disponible sobre el mirabegrón, con el fin de analizar su eficacia, seguridad y coste, y así estimar su papel en la farmacoterapia actual.Metodología: La eficacia y seguridad del mirabegrón se analizó mediante una evaluación de la evidencia científica. El coste de las diferentes alternativas farmacológicas se calculó en base a sus dosis diarias definidas (DDD) y el precio de venta del laboratorio. Resultados: Tres ensayos clínicos aleatorizados, controlados con placebo, de 12 semanas de duración, apoyan el uso del mirabegrón en el tratamiento del síndrome de vejiga hiperactiva. Los tres comparten las mismas variables principales de eficacia (número de episodios de incontinencia/24 h y número de micciones/24 h). Los datos de eficacia a largo plazo se basan en un estudio de seguridad de 12 meses de duración en el que los resultados de eficacia se medían como variables secundarias. En todos los estudios, el mirabegrón mostró un efecto significativo pero modesto. Entre los efectos adversos más frecuentes se detectaron hipertensión, aumento de glucosa en sangre, dolor de cabeza, infecciones del tracto urinario, estreñimiento y taquicardia. Se debe prestar especial atención a los eventos cardiovasculares. Conclusiones: La eficacia clínica del mirabegrón es muy modesta y comparable a la conseguida con el resto de fármacos aprobados para esta indicación. Además, presenta un mayor coste que otras alternativas terapéuticas. Los riesgos cardiacos e infecciones urinarias solo hacen posible considerarlo como  una alternativa a los anticolinérgicos cuando estos estén contraindicados, sean clínicamente ineficaces o sus efectos adversos sean inaceptables.

Topics: Acetanilides; Humans; Quality of Life; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To compare the efficacy of onabotulinumtoxinA, mirabegron, and anticholinergics in adults with idiopathic overactive bladder (OAB) using network meta-analysis (NMA).. Information sources were searched for blinded randomised controlled trials (RCTs), of ≥2 weeks duration, comparing any dose of onabotulinumtoxinA, eligible oral/transdermal anticholinergics, or mirabegron, with each other or placebo, in adults with OAB. Bayesian random-effects models were used to synthesise the results at week 12: NMA for responder analyses and network meta-regression (NMR) for change from baseline analyses. The NMR was used to adjust for differences in baseline severity between studies. Sensitivity analysis, excluding studies considered to be at a high risk of methodological bias, was conducted.. In all, 56 RCTs were included in the networks. For each outcome, results are reported for all licensed treatment doses. For each NMR, results are based on patients with an average number of episodes of the outcome at baseline. After 12 weeks, all treatments were more efficacious than placebo. Patients who received onabotulinumtoxinA (100 U) had, on average, the greatest reductions in urinary incontinence episodes (UIE), urgency episodes, and micturition frequency, and the highest odds of achieving decreases of 100% and ≥50% from baseline in UIE/day. When comparing onabotulinumtoxinA with other pharmacotherapies, mean differences favoured onabotulinumtoxinA 100 U over all comparators for UIE and urgency episodes (credible intervals excluded zero) and all but two of the comparators for micturition frequency. OnabotulinumtoxinA 100 U was also associated with higher odds of achieving a 100% and ≥50% decrease in UIE/day than most other licensed treatments in the network. The exclusion of studies with a high risk of bias had little impact on the conclusions.. The results indicate that, after 12 weeks, onabotulinumtoxinA 100 U provides greater relief of OAB symptoms compared with most other licensed doses of other pharmacotherapies in the network.

Topics: Acetanilides; Administration, Oral; Botulinum Toxins, Type A; Cholinergic Antagonists; Humans; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

The mainstay of overactive bladder treatment is the use of anticholinergic medication with its common side effects well known. This review focused on three less well-known safety issues when treating OAB. Areas covered: Patients with increased anticholinergic load are at risk of cognitive decline, dementia or even death. The elderly are particularly at risk due to polypharmacy. Botulinum toxin carries the risk of high urinary residuals, urinary tract infection and need to self catheterise. The use of vaginal oestrogens may improve OAB symptoms, but there is concern in those with a history of breast cancer. Studies have shown that the systemic absorption is negligible and does not increase the risk of recurrence. Expert Opinion: Improvement in assessing anticholinergic load is needed with the development of a universal drug scale. To avoid increasing load, Mirabegron or botulinum toxin can be used instead. There is no consensus of the use of prophylactic antibiotics when injecting botulinum toxin and at what residual to initiate self catheterisation. Despite evidence showing that the use of vaginal oestrogens is safe in those with a history of cancer, it is not fully supported by any health body. Further work is needed in those using aromatase inhibitors.

Topics: Acetanilides; Aged; Botulinum Toxins; Cholinergic Antagonists; Estrogens; Humans; Polypharmacy; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Mirabegron is established as an alternative monotherapy to antimuscarinics for the treatment of overactive bladder (OAB) symptoms. Initial studies focused on Western populations, but over the past few years other populations and subpopulations have been evaluated. Areas covered: The authors' knowledge of the literature was used to develop the manuscript alongside a PubMed search ('mirabegron and clinical trial' and 'overactive bladder') to select independent studies of mirabegron. Up-to-date information is provided about the most recent mirabegron clinical trial and real-world efficacy, safety and tolerability data in a variety of patient populations with OAB, including those from different geographic areas, men, the elderly, and those with poor tolerability to antimuscarinics. Expert commentary: Improvements in efficacy parameters in patients with OAB at mirabegron doses approved for clinical use (25 and 50 mg/day) are also associated with clinically meaningful benefits according to patient-reported outcomes. Mirabegron has a favorable safety and tolerability profile, particularly compared with antimuscarinics, for dry mouth, constipation, and many CNS effects, which is maintained over 1 year. A growing body of evidence suggests that mirabegron represents a new treatment option for a broad range of patients with OAB.

Topics: Acetanilides; Aged; Asia; Humans; Male; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Study the efficacy and adverse events of different pharmacological lines in the treatment of idiopathic overactive bladder (iOAB).. PubMed research on meta-analyses and randomized controlled trials (RCT) focused on the efficacy and adverse effects of anticholinergics, botulinum toxin and mirabegron since 2005.. Ten meta-analyses of anticholinergics were selected; 16 randomized controlled trials (ERC) comparing botulinum toxin A to either anticholinergic or placebo and 10 ERC studying mirabegron. All the molecules studied showed efficacy compared to placebo in the treatment of iOAB. Anticholinergics remain the first-line pharmacological treatment allowing a significant reduction in the number (nb) of incontinence (-5/week) and in the number of urination (-4/week) as well as a perception of subjective improvement of the symptoms reported by 56 % of the patients treated against 41 % for the placebo group (RR: 1.39 [95 % CI: 1.28-1.51]). The most commonly reported side effect is dry mouth (30 % vs. 8 % in the placebo group). Injections of botulinum toxin A appear to be relatively comparable to anticholinergics in the first line with a decrease in urinary emergency incontinence (UTI) of 3.3/d in the toxin group versus 3.4/d in the anticholinergic group (P=0.81). There was also a higher rate of complete resolution of urinary incontinence in the toxin group (27 % vs. 13 % P=0.03) but significant adverse effects such as lower urinary tract infections (33 % vs. 13 % P>0.01). And the risk of using self-catheterization (5 % vs. 0 % P=0.01). In view of the invasive character of the toxin injections and their side effects, this treatment remains a 2nd line therapy. The same is true for mirabegron: similar efficacy (IUU number in the mirabegron group 50mg -1.74 vs. -1.53 In the solifenacin group 5mg, P>0.5) but different side effects with arterial hypertension (the oral dryness rate being comparable to that in the placebo group). The choice of use of anticholinergic or mirabegron should be based on the balance of efficacy/tolerance to be estimated for each patient.. The different molecules have shown their efficacy in the treatment of iOAB with acceptable tolerance. There is a lack of direct comparisons between treatments available. Further studies are needed to evaluate the possible interest of a combination of these molecules as well as the search for predictive factors of response to these different therapies.

Topics: Acetanilides; Botulinum Toxins, Type A; Cholinergic Antagonists; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

Mirabegron is a relatively new drug introduced to treat overactive bladder syndrome. It can be used either on its own or as part of a combination. This drug has been extensively studied, with a good number of Phase II and Phase III trials showing promising outcomes. These studies show that mirabegron is an effective, well-tolerated drug, which could have some adverse effects of concern. In this review, we look at the trials on mirabegron, as well as its pharmacokinetics, mechanism of action, and side effects as documented in the literature.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Thiazoles; Urinary Bladder, Overactive

Overactive bladder is a common symptom complex with health related quality of life impacts on the individual as well as utilizing health resources. Antimuscarinic therapy has been the mainstay of treatment and is well supported within the literature and guidelines. However, compliance is poor due to lack of efficacy and adverse events leading to the development of novel therapies. Mirabegron, the B3-adrenoreceptor agonist has emerged as an evidence-based alternative first or second line therapy. Two decades after its first clinical application for overactive bladder, intravesical botulinum toxin is now an important part of any clinician's armamentarium for refractory cases. Despite these therapeutic options many patients find therapies ineffective or have adverse events. This has resulted in ongoing developments in the understanding of overactive bladder, potential new drugs and combination therapies, which this paper intends to review.

Topics: Acetanilides; Drug Design; Humans; Muscarinic Antagonists; Quality of Life; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Mirabegron, the first β3-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms. Because β3-adrenoceptors are expressed in cardiovascular (CV) tissues, there are concerns that OAB treatment with β3-adrenoceptor agonists may affect the heart and vasculature.. To provide a summary of CV effects of β3-adrenoceptor agonists in clinical studies.. A systematic literature search from inception until November 2014 was performed on studies in PubMed and Medline.. Twenty papers, published between 1994 and 2014, were identified: mirabegron (16), solabegron (2), AK-677 (1), and BRL35135 (1). More detailed CV data from mirabegron studies were available in online regulatory documents filed with the US Food and Drug Administration and the UK National Institute for Health and Care Excellence.. The CV safety of mirabegron appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, currently first-line therapy for OAB.. In this review we looked at the cardiovascular (CV) effects of β3-adrenoceptor agonists used for the treatment of overactive bladder (OAB). The CV safety of mirabegron (the only clinically approved β3-adrenoceptor agonist) appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, the current first-line therapy for OAB.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aniline Compounds; Benzoates; Biphenyl Compounds; Blood Pressure; Cardiovascular Diseases; Electrocardiography; Heart Rate; Humans; Thiazoles; Urinary Bladder, Overactive

Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and β3-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice.. Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged ≥65 and ≥75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described.. Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged ≥65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4 mg than with mirabegron 25 mg or 50 mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50 mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged ≥65 years.. Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to-risk ratio and therefore be considered as an alternative to antimuscarinics for older patients.

Topics: Acetanilides; Administration, Oral; Adrenergic beta-Antagonists; Aged; Benzhydryl Compounds; Blood Pressure; Clinical Trials as Topic; Constipation; Female; Heart Rate; Humans; Male; Middle Aged; Muscarinic Antagonists; Prospective Studies; Retrospective Studies; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

OnabotulinumtoxinA and mirabegron have recently gained marketing authorisation to treat symptoms of overactive bladder (OAB).. To evaluate the relative efficacy of mirabegron and onabotulinumtoxinA in patients with idiopathic OAB.. Network meta-analysis.. A search of 9 electronic databases, review documents, guidelines and websites.. Randomised trials comparing any licensed dose of onabotulinumtoxinA or mirabegron with each other, anticholinergic drugs or placebo were eligible (19 randomised trials were identified). 1 reviewer extracted data from the studies and a second reviewer checked the data. Candidate trials were assessed for similarity and networks were developed for each outcome. Bayesian network meta-analysis was conducted using both fixed-effects and random-effects models. When there were differences in mean baseline values between mirabegron and onabotulinumtoxinA trials they were adjusted for using network meta-regression (NMR).. No studies directly comparing onabotulinumtoxinA to mirabegron were identified. A network was created for each of the 7 outcomes, with 3-9 studies included in each individual network. The trials included in the networks were broadly similar. Patients in the onabotulinumtoxinA trials had more urinary incontinence and urgency episodes at baseline than patients in the mirabegron trials and these differences were adjusted for using NMR. Both onabotulinumtoxinA and mirabegron were more efficacious than placebo at reducing the frequency of urinary incontinence, urgency, urination and nocturia. OnabotulinumtoxinA was more efficacious than mirabegron (50 and 25 mg) in completely resolving daily episodes of urinary incontinence and urgency and in reducing the frequency of urinary incontinence, urgency and urination. NMR supported the results of the network meta-analysis.. In the absence of head-to-head trials comparing onabotulinumtoxinA to mirabegron, this indirect comparison indicates that onabotulinumtoxinA may be superior to mirabegron in improving symptoms of urinary incontinence, urgency and urinary frequency in patients with idiopathic OAB.

Topics: Acetanilides; Botulinum Toxins, Type A; Humans; Nocturia; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

We have reviewed the safety and tolerability of β3-adrenoceptor agonists, specifically mirabegron and solabegron, a newly emerging drug class for the treatment of the overactive bladder syndrome. We discuss them mechanistically in the context of expression and other preclinical data.. Based on a systematic PubMed search, incidence of overall adverse events, hypertension, dry mouth, and constipation are comparable between mirabegron or solabegron and placebo. Hypertension is the most frequently observed adverse event, but has a similar incidence with mirabegron and placebo. Nevertheless, severe uncontrolled hypertension has become a contraindication for use of mirabegron based on observation of severe hypertension in association with mirabegron exposure. The overall incidence of adverse events is also similar between mirabegron and the muscarinic receptor antagonist tolterodine, but the incidence of dry mouth is much lower with mirabegron.. The high β3-adrenoceptor mRNA expression in the human ovaries is not associated with reproductive side effects. Generally, β3-adrenoceptors exhibit a rather restricted expression in human tissues, which may explain the overall good tolerability of agonists acting on this receptor. We propose that expression profiles and functional preclinical studies can be important tools in the prediction of adverse event profiles in first-in-class drugs.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aniline Compounds; Animals; Benzoates; Biphenyl Compounds; Gene Expression Profiling; Humans; Receptors, Adrenergic, beta-3; Thiazoles; Urinary Bladder, Overactive

Overactive Bladder (OAB) is a clinical syndrome describing the symptom complex of urgency, with or without urgency incontinence and is usually associated with frequency and nocturia. Antimuscarinics are currently the most widely prescribed drugs for OAB although persistence with medication is often limited due to lack of efficacy or intolerable adverse effects. Mirabegron is β3 adrenoreceptor agonist that is the first new drug licensed for the management of overactive bladder (OAB) in over 30 years.. This review provides a comprehensive overview of the mirabegron clinical trials programme, including Phase II, III and IV studies with a particular focus on tolerability and safety. A literature search was performed in Pubmed using the key words 'mirabegron', 'overactive bladder', 'β3 adrenoceptor agonist' and 'detrusor overactivity' with no restriction on dates.. The extensive clinical trial programme has shown mirabegron to be safe and efficacious in the treatment of OAB symptoms and the evidence would suggest that it offers an effective alternative to antimuscarinic therapy.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Humans; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive

To critically analyse available phase II and III randomised control trials (RCTs) reporting clinical data about the efficacy and tolerability of Mirabegron (a β₃-adrenoceptor agonist) in the treatment of overactive bladder (OAB) syndrome. A review of the literature was performed in September 2013 using the MEDLINE database. A 'free text' protocol was used for the search strategy using 'overactive bladder' and 'Mirabegron' as keywords. Subsequently, the searches were pooled and limited to phase II and III RCTs. Two phase II and five phase III RCTs were selected and analysed. The available phase II studies showed the efficacy and tolerability of different doses of Mirabegron compared with placebo. Moreover, a dose-ranging study showed that 50 mg once daily should be considered the most promising dose for clinical use. The 12-week phase III studies confirmed the effectiveness of Mirabegron to significantly reduce the mean number of incontinence episodes/24 h and the mean number of micturitions/24 h compared with placebo. A post hoc analysis confirmed that favourable results with Mirabegron were reported both in patients with OAB who were antimuscarinic naïve and in those who had discontinued prior antimuscarinic therapy. Moreover, a phase III trial showed the safety and tolerability of 12-month treatment of Mirabegron. Discontinuation due to adverse events was low both using the 50 and 100 mg dose of Mirabegron. Mirabegron is the first of a new class of drugs for the treatment of OAB able to influence non-voiding activity and produce an increased storage capacity and inter-void interval. Recently published phase II and III RCTs have shown that the β₃-adrenoceptor-selective agonist, Mirabegron, is an effective and safe drug for the symptomatic treatment of OAB syndrome. Mirabegron represents a valid medical option both for patients with OAB who are antimuscarinic naïve, as well as in those where antimuscarinics are ineffective or not tolerated.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Administration, Intravesical; Aged; Behavior Therapy; Botulinum Toxins, Type A; Cholinergic Antagonists; Combined Modality Therapy; Cooperative Behavior; Female; Humans; Interdisciplinary Communication; Male; Thiazoles; Urinary Bladder; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence

Overactive bladder (OAB) is a clinical syndrome describing the symptom complex of urgency, with or without urgency incontinence, and is usually associated with frequency and nocturia. It is a common, under-diagnosed and therefore under-treated condition that can have a detrimental effect on physical functioning and psychological well-being. Initial treatment of OAB includes lifestyle advice, behavioural modifications, bladder retraining and pelvic floor muscle training, usually in combination with antimuscarinic agents. The β3-adrenoceptor agonist mirabegron is the first of a new class of drugs that are now competing with the more established antimuscarinics for the treatment of OAB. Our review focuses on the mode of action, efficacy and tolerability of mirabegron. The place of β3-adrenoceptor agonists in the treatment algorithm of OAB is discussed, considering the adverse events associated with antimuscarinics. Drug therapy tailored to different population groups appears a promising future prospect. Development of other β3-adrenoceptor agonists is expected, and combination therapy regimens might revolutionise the treatment of OAB.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder (OAB) is a common problem which can have disastrous effects on the quality of life of the sufferer. There are established treatments for the problem but they have significant adverse effects. Better drugs and new treatment modalities are necessary to deal with OAB.. Antimuscarinics, mirabegron and intravesical injection of botulinum toxin A are established treatments for OAB. Sacral neuromodulation is more invasive but has been successful in treating OAB. Phase II and III trials are in progress for newer β3-agonists and various combinations of antimuscarinics, β3-agonists and antidiuretics. Targeted secretion inhibitors (TSI) can increase efficacy and reduce adverse effects. Liposome integrated botulinum toxin A has an advantage of effective administration by intravesical instillation. Both medicines are in Phase II trials. Many other drugs which have promising results are discussed.. Newer antimuscarinics have better tolerability. Long-term data for mirabegron has shown that it is more effective in severe OAB. Combination drugs may prove to be more effective with less adverse effects. Emerging treatments with TSI, lipotoxin and gene therapy appear promising.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Botulinum Toxins, Type A; Drug Design; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Quality of Life; Thiazoles; Urinary Bladder, Overactive

Mirabegron, a potent and selective β3-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB). We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating OAB.. A literature review was performed to identify all published randomized double-blind, placebo-controlled phase III trials of mirabegron for the treatment of OAB. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. A systematic review and meta-analysis of phase III trials were conducted.. Four publications involving a total of 5,761 patients were used in the analysis, including four phase III RCTs that compared mirabegron with placebo. We found that mirabegron was effective in treating OAB in our meta-analysis. Co-primary efficacy end points: the mean number of incontinence episodes per 24 h (the standardized mean difference (SMD) = -0.44, 95 % confidence interval (CI) -0.59 to -0.29, p < 0.00001); the mean number of micturitions per 24 h (SMD = -0.62, 95 % CI -0.80 to -0.45, p < 0.00001) and key secondary efficacy end points: mean volume voided per micturition; mean number of urgency episodes per 24 h indicated that mirabegron was more effective than the placebo. Safety assessments included common treatment-emergent adverse events (TEAEs) [OR 1.10, 95 % CI 0.93-1.31, p = 0.25), hypertension, cardiac arrhythmia TEAEs, urinary retention and discontinuations due to adverse event indicated that mirabegron was well tolerated.. This meta-analysis indicates that mirabegron to be an effective and safe treatment for OAB symptoms with a low occurrence of side effects. It offers promise as an effective oral agent for the treatment of OAB with a distinct efficacy/tolerability balance.

Topics: Acetanilides; Clinical Trials, Phase III as Topic; Humans; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive; Urination

Mirabegron is a novel β3-adrenoceptor agonist recently approved by Japanese, American, and European authorities for overactive bladder (OAB) therapy. Here we review existing knowledge on this new class of medication, analyze existing literature on the topic, and make recommendations regarding its administration and necessary future studies.. We reviewed the current literature and analyzed mirabegron efficacy, safety, and suitability for treating OAB symptoms. We performed a systematic search of Medline/PubMed, and Embase. Studies exploring mechanisms involved in the effects of mirabegron were included. Searches were limited to the English language.. Two phase II and two large-scale phase III multinational randomized controlled trials have supported mirabegron efficacy and tolerability with up to 12 weeks of therapy in OAB patients. The reported frequency and severity of treatment-emergent and serious adverse events were similar to antimuscarinics but with more than threefold lower incidence of dry mouth than with tolterodine. However, effects on the cardiovascular system, cognitive functions, pharmacokinetic interactions with other drugs, and long-term adverse events have not yet been fully investigated.. Anticholinergic drugs should remain the first-line pharmacologic treatment for OAB until head-to-head comparative study eventually shows that mirabegron has equivalent or superior efficacy. However, it seems logical to use mirabegron as second-line treatment of OAB in patients who are poor responders or intolerant to anticholinergics.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Dose-Response Relationship, Drug; Female; Humans; Muscarinic Antagonists; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Mirabegron, the first β3 -adrenoceptor agonist to enter clinical practice, has a different mechanism of action from antimuscarinic agents. This review presents data on the efficacy, safety, and tolerability of mirabegron in studies conducted to date.. All clinical data on mirabegron that are currently in the public domain are included, including some in-press manuscripts.. In Phase III clinical trials in patients with overactive bladder (OAB), mirabegron at daily doses of 25, 50, and 100 mg demonstrated significant efficacy in treating the symptoms of OAB, including micturition frequency, urgency incontinence, and urgency. Significant improvements in micturition frequency, urgency incontinence, and mean volume voided/micturition were seen as early as the first assessment (week 4) for mirabegron 50 and 100 mg, and were maintained throughout treatment. Responder analyses showed a significant improvement with mirabegron 50 and 100 mg in terms of dry rates, ≥50% reduction in mean number of incontinence episodes/24 hr, and the proportion of patients with ≤8 micturitions/24 hr at final visit. The benefit of mirabegron 50 and 100 mg was also evident in patients ≥65 years of age, and in both treatment-naïve patients and those who previously discontinued antimuscarinic therapy. These data therefore demonstrate a clinically meaningful benefit with mirabegron in the objective endpoints of OAB. Assessment of measures of health-related quality of life and treatment satisfaction showed that patients perceived treatment with mirabegron as meaningful. In OAB clinical trials of up to 12 months mirabegron appeared to be well tolerated. The most common adverse events (AEs) observed with mirabegron in clinical trials of up to 12 months were hypertension, nasopharyngitis, and urinary tract infection. The incidence of dry mouth was similar to placebo, and was between three and fivefold less than for tolterodine extended release 4 mg. Since dry mouth is the most bothersome AE associated with antimuscarinic drugs and often a reason for treatment discontinuation, mirabegron may be a valuable treatment option for these patients.. In Phase III clinical trials, mirabegron at daily doses of 25, 50, and 100 mg demonstrated significant efficacy in treating symptoms of OAB and, at doses of 50 and 100 mg, demonstrated significant improvements versus placebo on key secondary endpoints, as early as the first assessment (week 4), and these were maintained throughout treatment. In OAB clinical trials of up to 12 months, mirabegron appeared to be well tolerated.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Humans; Thiazoles; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics; Urological Agents

Overactive bladder (OAB) treatment guidelines recommend antimuscarinics as first-line pharmacologic therapy. Mirabegron is a first-in-class β3-adrenoceptor agonist licensed for the treatment of OAB and has shown to be well tolerated and effective in the treatment of OAB symptoms.. To assess the relative efficacy and tolerability of OAB medications, specifically mirabegron 50 mg versus antimuscarinics in patients with OAB.. A systematic literature search was performed on published peer-reviewed articles from 2000 to 2013. This review included randomised controlled trials (RCTs) studying changes in symptoms (micturition frequency, incontinence, and urgency urinary incontinence [UUI] episodes) and incidence of the most frequently reported adverse events (dry mouth, constipation) associated with current OAB medications. The following drugs were considered in addition to mirabegron: darifenacin, tolterodine immediate release (IR) and extended release (ER), oxybutynin IR/ER, trospium, solifenacin, and fesoterodine. Bayesian mixed treatment comparisons (MTCs) were performed for efficacy (micturition, incontinence, UUI) and tolerability (dry mouth, constipation, blurred vision).. Overall, 44 RCTs involving 27,309 patients were included. The MTCs showed that mirabegron 50 mg was as efficacious as antimuscarinics in reducing the frequency of micturition incontinence and UUI episodes, with the exception of solifenacin 10 mg that was more efficacious than mirabegron 50 mg in improving micturition frequency and frequency of UUI. Mirabegron 50 mg had an incidence of dry mouth similar to placebo and significantly lower than all included antimuscarinics.. Mirabegron 50 mg had similar efficacy to most antimuscarinics and lower incidence of dry mouth, the most common adverse event reported with antimuscarinics and one of the main causes of discontinuation of treatment. Despite being a powerful tool for evidence-based health care evaluation, the Bayesian MTC method has limitations. Further head-to-head comparisons between mirabegron and antimuscarinics should be conducted to confirm our results.

Topics: Acetanilides; Humans; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive

Long-term persistence with pharmacotherapy for overactive bladder (OAB) requires a drug with an early onset of action and good efficacy and tolerability profile. Although antimuscarinics improve OAB symptoms within 1-2 weeks of initiating treatment, adherence after 3 months is relatively poor due to bothersome side effects (e.g., dry mouth and constipation). Mirabegron, a β3-adrenoceptor agonist, has demonstrated significant improvements in key symptoms of OAB and good tolerability after 12 weeks in Phase III studies.. This was a prespecified pooled analysis of three randomized, double-blind, placebo-controlled, 12-week studies, and a Phase II study, to evaluate efficacy and tolerability of mirabegron 25 and 50 mg versus placebo. The main efficacy endpoints were change from baseline to week 1 (Phase II only), week 4, and final visit in mean number of incontinence episodes/24 h, micturitions/24 h, and mean volume voided/micturition (MVV).. A significant benefit for mirabegron 25 and 50 mg versus placebo was evident at the first assessment point, 4 weeks after initiation of therapy, in Phase III studies for incontinence, micturitions, and MVV. The earliest measured benefit was after 1 week, in the Phase II study. Quality-of-life parameters also significantly improved with mirabegron 25 and 50 mg as early as week 4. Significant benefits continued throughout the studies. Mirabegron was well tolerated.. The early onset of action and good overall efficacy and tolerability balance that mirabegron offers may lead to high rates of persistence with mirabegron in the long-term treatment of OAB.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Young Adult

Overactive bladder (OAB) and urinary incontinence, although not life-threatening, are very bothersome chronic health conditions. The limitations of current pharmacological treatment urge the need for novel drugs with alternative mechanisms of action. Huge efforts in this area of research led to the synthesis of several selective and potent β3-adrenoceptor agonists that gained relevance through research during the late 80s and 90s. Mirabegron was the first compound of this new class of drugs that showed preclinical efficacy in several models of storage bladder dysfunction, together with a favorable human pharmacological profile. Having passed the proof-of-concept stage, an extensive clinical development and pharmacology program was performed during the last 10 years, involving >10,000 individuals, before mirabegron was granted marketing approval.. In this case history, the authors review the milestones in mirabegron's discovery based on a systematic literature review.. Thanks to its tolerability and safety/efficacy balance, mirabegron has potential to fill a need for new treatment options for OAB, and paves the way for further development of a completely new class of drugs aimed to treat this condition. However, the exact role of mirabegron in clinical practice has yet to be defined. Further studies are needed in order to clarify, together with post-launch information, critical safety issues and cost-effectiveness in head-to-head comparison with current standard treatments.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Humans; Receptors, Adrenergic, beta-3; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urinary Tract; Urological Agents

mirabegron is a β3-adrenoceptor agonist developed for the treatment of symptoms of overactive bladder (OAB). As the prevalence of OAB increases with age, a prospective subanalysis of individual and pooled efficacy and tolerability data from three 12-week, randomised, Phase III trials, and of tolerability data from a 1-year safety trial were conducted in order to evaluate the efficacy and tolerability of mirabegron in subgroups of patients aged ≥65 and ≥75 years.. primary efficacy outcomes were change from baseline to final visit in the mean number of incontinence episodes/24 h and the mean number of micturitions/24 h. Tolerability was assessed by the incidence of treatment-emergent adverse events (TEAEs).. over 12 weeks mirabegron 25 mg and 50 mg once-daily reduced the mean numbers of incontinence episodes and micturitions/24 h from baseline to final visit in patients aged ≥65 and ≥75 years. Mirabegron was well tolerated: in both age groups, hypertension and urinary tract infection were among the most common TEAEs over 12 weeks and 1 year. The incidence of dry mouth, a typical anticholinergic TEAE, was up to sixfold higher among the older patients randomised to tolterodine than any dose of mirabegron.. these analyses have demonstrated the efficacy of mirabegron over 12 weeks and the tolerability of mirabegron over 12 weeks and 1 year in OAB patients aged ≥65 and ≥75 years, supporting mirabegron as a therapeutic option in older patients with OAB.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Age Factors; Aged; Clinical Trials, Phase III as Topic; Humans; Randomized Controlled Trials as Topic; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

Mirabegron is a selective β3-adrenergic receptor agonist recently developed for the treatment of patients with overactive bladder (OAB), which offers an alternative pharmacological option to the well-established treatment with antimuscarinics (AMs).. This review offers an explanation of the mechanism of action, of the pharmacokinetics and pharmacodynamics of mirabegron and gives readers a complete overview of Phase II and III studies on the clinical efficacy, tolerability and safety of this agent in the setting of OAB treatment.. Both Phase II and III trials have shown that mirabegron is efficacious and safe in treating patients with OAB. Future research should focus on the assessment of mirabegron concentrations in the CNS and on the evaluation of the potential of the combination of mirabegron with AMs. Another field for future research is represented by the investigation of the interaction of mirabegron with CYP2D6 inhibitors. Furthermore, current literature completely lacks studies on the efficacy and safety of mirabegron in the pediatric population and such trials are awaited.

Topics: Acetanilides; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive

Overactive bladder is defined by ICS as urgency frequency and nocturia, with or without urgency urinary incontinence in the absence of urinary tract infection, or other obvious causative pathology Lower urinary tract symptoms (LUTS) are highly prevalent, especially in aging populations. Epidemiological studies reported LUTS in 62% of men and 67% of women, rising to 81% and 79%, respectively in adults over 60 years old. However the actual burden of LUTS remains relatively unrecognized. LUTS, mainly due to considerable distress including almost all aspects of social functioning, impact on sleep and mental health, may significantly affect quality of life. Management of LUTS including OAB has undergone dramatic changes since 1972, when the first antimuscarinic drug-oxybutynin, was introduced into clinical practice. In the last two decades, six new antimuscarinic drugs entered OAB field and this was accompanied by introduction of botulinum toxin into clinical practice in patients resistant to or not compliant with antimuscarinics. Nowadays, it is recognized that OAB is progressive, age-related and non sex-specific condition with most patients experiencing a combination of storage, voiding and post-micturition symptoms. In 2013, the next step was taken, with new therapeutic options for OAB, enabling an even more patient-tailored approach. This was possible for both, male and female OAB sufferers with new class of oral 3 adrenoreceptor agonist (mirabegron). This drug, by stimulation of 3-adrenoceptors, couples via Gs proteins to adenylyl cyclase, what results in an increase of intracellular cAMP levels and a subsequent activation of cAMP-dependent protein kinase A, which then phosphorylates myosin light chain kinase responsible for inhibition of calcium-calmodulin dependent interaction of myosin with actin. Moreover the cAMP increase also leads to the reduction of cytoplasmic Ca2+ concentration by removal of calcium ions from cytoplasm. These both actions result in a significant increase in the storage bladder capacity and by this interval between micturitions is prolonged. Mirabegron was evaluated in three 12-week, double blind, randomized, placebo controlled, parallel-group, multicenter clinical trials in OAB patients with symptoms of urge urinary incontinence, urgency and frequency - study 046, 047 and 074. It should be pointed out that efficacy of mirabegron was maintained through the entire 12-month period in phase Ill long-term study Discoveries on the phy

Topics: Acetanilides; Adrenergic beta-3 Receptor Antagonists; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence

Overactive bladder is a difficult to treat condition affecting a large proportion of adults resulting in considerable economic impact to society. First-line treatments such as behavioral therapy or antimuscarinic medication are frequently not effective in adequately controlling symptoms or have intolerable side effects. Patients subsequently require second-line therapy including, sacral neuromodulation through either posterior tibial nerve stimulation or sacral nerve stimulation or intra-detrusor injection of Onabotulinumtoxin-A. Mirabegron, a relatively new drug in a separate class, is also employed in the treatment of overactive bladder. The question of which novel therapy to initiate depends on several factors including patient preference, effectiveness and cost. The purpose of this review is to present and discuss the most recent studies pertaining to the cost-effectiveness of novel therapies for overactive bladder.

Topics: Acetanilides; Adult; Behavior Therapy; Botulinum Toxins, Type A; Cost-Benefit Analysis; Electric Stimulation Therapy; Humans; Muscarinic Antagonists; Thiazoles; Tibial Nerve; Urinary Bladder, Overactive

To present a systematic review assessing the efficacy and safety of mirabegron for overactive bladder (OAB).. A literature search was performed using the Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded. The literature reviewed included meta-analyses, randomized and nonrandomized prospective studies. We utilized mean difference (MD) to measure the mean number of incontinence episodes and the mean number of micturitions, and OAB questionnaire (OAB-q) and odds ratio (OR) to measure adverse events rates. We used the Cochrane Collaboration's Review Manager 5.1 software for statistical analysis.. We identified six publications that strictly met our eligibility criteria. Meta-analysis of extractable data showed that mirabegron was more effective than placebo in treating OAB despite different drug dosages in the efficacy end points: mean number of incontinence episodes per 24 h (MD -0.54; 95% CI -0.63, -0.45; p = 0.001), mean number of micturitions per 24 h (MD -0.55; 95% CI -0.63, -0.47; p = 0.001), OAB-q (MD -4.49; 95% CI -6.27, -2.71; p = 0.001) and adverse events (OR 0.99; 95% CI 0.83, 1.19; p = 0.92). When compared to tolterodine, mirabegron was more effective in terms of mean number of incontinence episodes per 24 h (MD -0.25; 95% CI -0.43, -0.06; p = 0.009). However, there were no differences between mirabegron and tolterodine in mean number of micturitions per 24 h (MD -0.17; 95% CI -0.35, 0.01; p = 0.07) and OAB-q (MD -1.09; 95% CI -2.51, 0.33; p = 0.13). Mirabegron also had a lower adverse reaction rate (OR 0.9; 95% CI 0.8, 1.0; p = 0.04).. In this diverse population, mirabegron was an effective and safe pharmacologic therapy for OAB.

Topics: Acetanilides; Benzhydryl Compounds; Cresols; Humans; Muscarinic Antagonists; Odds Ratio; Phenylpropanolamine; Prospective Studies; Research Design; Software; Surveys and Questionnaires; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

To summarize recent data on the medical treatment of men with incontinence due to overactive bladder or to stress urinary incontinence published in peer-reviewed journals.. Previous randomized controlled trials have shown that both antimuscarinic drugs and α1-adrenoceptor blockers can be useful for treatment of male lower urinary tract symptoms, including the overactive bladder syndrome, and that combination of the two principles may offer additional benefits over monotherapy with either agent. This has been further confirmed in several recent studies. There seems to be an associated increase in postvoid residual urine volume by the combinations, but not a significantly increased risk of retention. The efficacy of other combinations, for example, α1-adrenoceptor blocker and 5α-reductase inhibitor, has also been further documented. Recent evidence supports the use of mirabegron, alone or in combination with solifenacin, as a treatment alternative of male overactive bladder syndrome. Monotherapy with phosphodiesterase 5 inhibitors seems to be as effective as α1-adrenoceptor blockers in male lower urinary tract symptoms. Only a few recent studies have been performed on the pharmacological treatment of male stress urinary incontinence, confirming that duloxetine had a modest positive effect in men with postprostatectomy incontinence.. For treatment of storage symptoms in men with lower urinary tract symptoms, combinations of antimuscarinics and α1-adrenoceptor blockers have produced the most promising results. Duloxetine exerts only modest relief of male stress urinary incontinence, but may be recommended in some patients.

Topics: 5-alpha Reductase Inhibitors; Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Muscarinic Antagonists; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence, Stress; Urinary Incontinence, Urge; Urological Agents

To review the literature regarding the efficacy and safety of mirabegron for the treatment of overactive bladder (OAB).. A literature search was performed using MEDLINE (PubMed) prior to December 31, 2013, using the terms "mirabegron" and "randomized-controlled trial.". All published, double-blind, randomized-controlled trials assessing mirabegron were included. Articles were reviewed and included if mirabegron was used as monotherapy and if the primary outcome analyzed drug efficacy.. The efficacy of mirabegron for the treatment of OAB has been demonstrated in the selected five randomized, placebo-controlled trials. The majority of these trials lasted 12 weeks and compared various doses of mirabegron with placebo and/or tolterodine extended-release (ER). Primary efficacy outcomes for the trials included mean number of micturitions per 24 hours and mean number of incontinence episodes per 24 hours. Included trials showed statistically significant reductions in both efficacy outcomes for various doses of mirabegron when compared with placebo.. Based on the trials reviewed, mirabegron has been efficacious in reducing mean number of micturitions and incontinence episodes per 24 hours, as well as in improving other secondary outcomes such as OAB symptoms and quality-of-life measures. Common adverse drug events seen with mirabegron include: hypertension, nasopharyngitis, urinary tract infections, headache, constipation, upper respiratory tract infection, arthralgia, diarrhea, tachycardia, abdominal pain, and fatigue. Given the efficacy and safety data currently available, mirabegron represents a reasonable alternative to antimuscarinics for patients with OAB. Future studies are needed to determine the utility of mirabegron for OAB in a variety of demographics.

Topics: Acetanilides; Humans; Thiazoles; Urinary Bladder, Overactive; Urological Agents

The bladder effects of isoprenaline, and selective β₁ and β₂-adrenoceptor agonists reported in early studies suggest that bladder β-adrenoceptors are atypical. Since there is a lack of alternatives to antimuscarinics in the treatment of overactive bladder symptoms, there has been an intensive search for new drug targets. Discovery of the β₃-adrenoceptor with high expression in the bladder suggested that this receptor, which mediates detrusor relaxation, could be a target for overactive bladder symptoms.. An overview of the published literature on β-adrenoceptor and the bladder was performed using MEDLINE. The United States Food and Drug Administration website, clinicaltrials.gov and controlled-trials.com online trial registries were searched for English language articles containing the terms β₃-adrenoceptors and β₃-adrenoceptor agonists. In addition, abstracts from recent international scientific meetings were searched for randomized, controlled trials of β₃-adrenoceptor agonists.. Stimulation of β₃-adrenoceptors relaxes detrusor smooth muscle, decreases afferent signaling from the bladder, improves bladder compliance upon filling and increases bladder capacity. Randomized, controlled trials show that the selective β₃-adrenoceptor agonist mirabegron, for which most information is available and which is approved in Japan, the United States and Europe, decreases the number of micturitions and incontinence episodes in a 24-hour period compared with placebo. The most common adverse effects recorded are dry mouth (placebo level) and gastrointestinal disturbances, rated as mild to moderate. Small increases in mean heart rate (1 beat per minute) and blood pressure (1 mm Hg) were noted in patients with overactive bladder.. Available information suggests that β3-adrenoceptor agonists may be a promising alternative to antimuscarinics in the treatment of overactive bladder. However, further clinical experience outside clinical trials and information on long-term use in terms of efficacy, safety and tolerability are warranted to optimally characterize the position of β3-adrenoceptor agonists in the treatment algorithm for overactive bladder.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Thiazoles; Urinary Bladder, Overactive

Overactive bladder (OAB) is defined by its hallmark symptom, urgency. It can be associated with urge urinary incontinence (UUI), and dramatically impact the patients' quality of life. Etiologies of OAB are numerous, and under this common wording, virtually all the population is covered (men as well as women, patients with or without neurogenic disease, and all age categories). OAB and UUI management have been historically based on non-interventional therapies, antimuscarinics, and surgery. In the last decade, innovations in the treatment of this highly prevalent condition have been multiple, and further insights came from various horizons (drug invention, innovative use of existing drugs, new medical devices, tissue engineering, gene and cell therapy). Notably, the use of BoNT and neuromodulation techniques have deeply modified the algorithm of specialized OAB management, delaying surgery indications and offering mini-invasive alternatives to patient refractory to behavioral and medical treatment. Whilst some of these techniques are about to reach maturity, numerous questions remain unsolved about their indications, long term effects, rank in the armamentarium, cost-effectiveness, hypothetical combination or sequential use. The present review depicts the actual wide range of options available for OAB management in adults, focusing on the latest evolutions. When relevant, a distinction was made between genders and OAB subtypes (idiopathic vs neurogenic) regarding treatment outcomes.

Topics: Acetanilides; Botulinum Toxins, Type A; Caffeine; Clinical Trials, Phase III as Topic; Drinking Behavior; Electric Stimulation Therapy; Electrodes, Implanted; Exercise Therapy; Female; Humans; Male; Multicenter Studies as Topic; Muscarinic Antagonists; Neurokinin-1 Receptor Antagonists; Pelvic Floor Disorders; Phosphodiesterase Inhibitors; Randomized Controlled Trials as Topic; Therapies, Investigational; Thiazoles; Urinary Bladder Neck Obstruction; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urologic Surgical Procedures

Mirabegron is a new once-daily, oral treatment for management of overactive bladder (OAB) that is approved in USA, EU and Japan. It activates β3 adrenoceptor to facilitate bladder filling and reduce mean micturition frequency with better safety profile than current treatment of antimuscarinic drugs.. The following article reviews the information available from published randomized trials on the metabolism and pharmacokinetics mirabegron. The reader will gain better insight into the variability in plasma exposure of mirabegron due to various causes. Propensity for drug interactions with mirabegron is low as its clearance involves multiple metabolic and excretory pathways. Mirabegron is generally well tolerated, but its pharmacokinetics is altered by dose and gender with implications for cardiovascular toxicity.. Mirabegron is a first-in-class of β3 adrenoceptor agonists that could offer an alternative to antimuscarinics for OAB patients. The marketed dose of 50 mg achieves primary efficacy endpoints but causes only modest improvement over placebo in terms of daily incontinence and voiding episodes. Involvement of saturable efflux transporters is indicated in oral bioavailability of mirabegron. It is well tolerated with hypertension, nasopharyngitis, urinary tract infection and headache being the most common side effects.

Topics: Acetanilides; Biological Availability; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Interactions; Europe; Humans; Japan; Kidney; Liver; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Thiazoles; United States; Urinary Bladder, Overactive

The new information generated over the last decade on the physiology/pharmacology of the normal bladder and on the pathophysiology of the overactive bladder has resulted in the introduction of a new therapeutic principle, β3-adrenoceptor (AR) agonism, and the approval of mirabegron, a selective agonist at β3-ARs. It may be asked in what respects the β3-AR agonists as a group, and mirabegron in particular, differ from the antimuscarinics, and what can clinically be gained by the β3-AR agonists. In this short review, the mechanisms of action, clinical efficacy, and adverse effect profiles of the two groups of drugs are compared and discussed.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Practice Guidelines as Topic; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive; Urination

To examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results.. This prespecified pooled analysis of three randomised, double-blind, placebo-controlled, 12-week studies, evaluated efficacy and safety of once-daily mirabegron 25 mg (safety analysis), 50 or 100 mg (efficacy and safety analyses) and tolterodine ER 4 mg (safety analysis) for the treatment of symptoms of overactive bladder (OAB). Co-primary efficacy measures were change from baseline to Final Visit in the mean number of incontinence episodes/24 h and mean number of micturitions/24 h. Key secondary efficacy end-points included mean number of urgency episodes/24 h and mean volume voided/micturitions, while other end-points included patient-reported outcomes according to the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) and responder analyses [dry rate (posttreatment), ≥ 50% reduction in incontinence episodes/24 h, ≤ 8 micturitions/24 h (post hoc analysis)]. The safety analysis included adverse event (AE) reporting, laboratory assessments, ECG, postvoid residual volume and vital signs (blood pressure, pulse rate).. Mirabegron (50 and 100 mg once daily) demonstrated statistically significant improvements compared with placebo for the co-primary end-points, key secondary efficacy variables, TS-VAS and responder analyses (all comparisons p < 0.05). Mirabegron is well tolerated and demonstrates a good safety profile. The most common AEs (≥ 3%) included hypertension, nasopharyngitis and urinary tract infection (UTI); the incidence of hypertensive events and UTIs decreased with increasing dose. For mirabegron, the incidence of the bothersome antimuscarinic AE, dry mouth, was at placebo level and of a lesser magnitude than tolterodine.. The efficacy and safety of mirabegron are demonstrated in this large pooled clinical trial dataset in patients with OAB.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Clinical Trials, Phase III as Topic; Cresols; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents; Young Adult

Mirabegron (YM178, Myrbetriq™, Betanis(®), Betmiga™) is a β3-adrenergic receptor agonist approved in several countries for the symptomatic treatment of adults with overactive bladder syndrome. In three 12-week, randomized, double-blind, placebo-controlled, multinational trials in patients with overactive bladder syndrome, oral mirabegron 25 or 50 mg once daily significantly reduced the adjusted mean number of incontinence episodes per 24 h (in patients with incontinence at baseline) and the adjusted mean number of micturition episodes per 24 h (in full trial populations) [coprimary endpoints]. Across trials, mirabegron 50 mg once daily also consistently significantly reduced urgency episodes and increased the volume of urine voided per micturition, generally in association with improved health-related quality of life (HR-QOL) and treatment satisfaction. Based on descriptive analyses from a 12-month trial, once-daily mirabegron 50 mg and tolterodine extended-release (ER) 4 mg were both efficacious in reducing urinary symptoms and improving HR-QOL. Mirabegron was generally well tolerated in the trials. Over 12 weeks, the adverse event rate with mirabegron 50 mg once daily was similar to that with placebo. During 12 months of treatment, 2.8 % of mirabegron 50 mg once daily recipients reported dry mouth compared with 8.6 % with tolterodine ER 4 mg once daily recipients. Mirabegron 50 mg once daily carries a low risk of QT interval prolongation. Thus, mirabegron is an efficacious new treatment for overactive bladder syndrome with a favourable tolerability profile.

Topics: Acetanilides; Humans; Randomized Controlled Trials as Topic; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To discuss the pharmacotherapeutic aspects of Mirabegron which is a first-in class novel β3 receptor agonist drug recently approved by the food and drug administration (FDA) for the treatment of overactive bladder (OAB).. We conducted a computerized search of the MEDLINE/PUBMED databases with the word Mirabegron, β3 receptor agonist and overactive bladder.. Effect of Mirabegron on β3 adrenergic receptor purportedly releases nitric oxide(NO) by an increase in intracellular Ca2+ through accumulation of cyclic adenosine monophosphate (cAMP). Along with NO which relaxes the detrusor muscle, it also releases an urothelial-derived inhibiting factor (UDIF) that inhibits contractions. It increases the bladder capacity by causing bladder relaxation during the storage phase.. Mirabegron appears to be a promising treatment in OAB patients by shifting its management from reducing detrusor over-activity to inducing relaxation. Also it lacks the troublesome side effects associated with the standard antimuscarinic management.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive

The overactive bladder syndrome and detrusor overactivity are conditions that can have major effects on quality of life and social functioning. Antimuscarinic drugs are still first-line treatment. These drugs often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, and alternatives are needed. The recognition of the functional contribution of the urothelium/suburothelium, the autonomous detrusor muscle activity during bladder filling and the diversity of nerve transmitters involved has sparked interest in both peripheral and central modulation of overactive bladder syndrome/detrusor overactivity pathophysiology. Three drugs recently approved for treatment of overactive bladder syndrome/detrusor overactivity (mirabegron, tadalafil and onabotulinum toxin A), representing different pharmacological mechanisms; that is, β-adrenoceptor agonism, phosphodiesterase type 5 inhibition, and inhibition of nerve release of efferent and afferent transmitters, all seem to have one effect in common: inhibition of the afferent nervous activity generated by the bladder during filling. In the present review, the different mechanisms forming the pharmacological basis for the use of these drugs are discussed.

Topics: Acetanilides; Afferent Pathways; Animals; Botulinum Toxins, Type A; Carbolines; Humans; Phosphodiesterase 5 Inhibitors; Tadalafil; Thiazoles; Urinary Bladder, Overactive

The lack of an alternative to antimuscarinics has led to the search for new drug targets for overactive bladder (OAB) symptoms. The presence of β-3 adrenoreceptors in the bladder has been confirmed, and they are known to have a role in bladder relaxation. Targeting these receptors improves bladder compliance on filling and increases bladder capacity. MEDLINE literature search on efficacy and safety of mirabegron was performed. The US Food and Drug Administration Web site, clinicaltrials.gov, and controlled-trials.com online trial registries were searched for English-language articles containing the term "mirabegron". Finally, abstracts from recent International scientific meetings were searched for randomised controlled trials (RCTs). Studies show that mirabegron reduces the number of micturitions and incontinence episodes in a 24-h period compared with placebo. Dry mouth and gastrointestinal disturbances are the most common side effects, but these have been rated as mild to moderate. A small rise in mean heart rate and blood pressure has been shown. Further investigations are ongoing and results are awaited. Although mirabegron is metabolised by CYP2D6, it is also thought to inhibit the activity of this enzyme. Therefore, potential drug interactions with other CYP2D6 substrates need to be further studied. Mirabegron is a promising alternative to antimuscarinics. Further information on its long-term use in terms of efficacy, safety, and tolerability is awaited.

Topics: Acetanilides; Adrenergic beta-Agonists; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Clinical Trials, Phase III as Topic; Humans; Muscle Relaxation; Muscle, Smooth; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive

Overactive bladder (OAB) is a common syndrome that affects both men and women. First-line therapies for the management of OAB symptoms consist of antimuscarinic agents and behavioral therapy, ideally used in combination. Although effective in improving OAB symptoms, the use of antimuscarinic therapy may be limited by side effects, contraindications, and insufficient response. Current second-line therapies include sacral nerve stimulation and percutaneous tibial nerve stimulation. These therapies have been shown to be useful in treating OAB symptoms, but are more invasive and time-consuming than medical therapy. Onabotulinum toxin A is currently under investigation for idiopathic OAB, as well as the β-3-adreno-renoreceptor agonists mirabegron and solabegron. The role of these agents, with different mechanisms of action, in the pharmacologic management of OAB remains to be determined, although they appear to be promising alternatives and possible adjuncts to current pharmacologic and behavioral therapy. This article discusses second-line and current and future therapies for the management of OAB symptoms.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aniline Compounds; Behavior Therapy; Benzoates; Biphenyl Compounds; Botulinum Toxins, Type A; Clinical Trials as Topic; Electric Stimulation Therapy; Humans; Muscarinic Antagonists; Neuromuscular Agents; Sacrum; Thiazoles; Tibial Nerve; Urinary Bladder, Overactive

In the United States, office visits for women seeking treatment for urinary incontinence more than doubled between 1994 and 2000, from 1845 per 100 000 women. This review article addresses treatment options for 2 common types of incontinence in women: stress urinary incontinence (SUI) and detrusor overactivity (DO), commonly referred to as urge urinary incontinence (UUI). In the past, those with SUI typically faced limited treatment options, such as Kegel exercises, pessaries, or major surgery (Burch or Marshall-Marchetti-Krantz operations). However, treatment options for women also included anticholinergic medications, behavioral therapy, and implantable neuromodulation. In recent years, more options have become available. For women with SUI, a variety of minimally invasive synthetic midurethral sling approaches (eg, retropubic, transobturator, and single incision) and office-based procedures (eg, periurethral injection of bulking agents and radiofrequency collagen denaturation [Renessa®; Novasys Medical]) are now offered. More outpatient options will hopefully be available soon, including an inflatable, free-floating balloon to act as a shock absorber, and injection of muscle-derived stem cells into the periurethral tissue. Women with UUI now have targeted options, such as posterior tibial nerve stimulation (PTNS) and intravesical injections of onabotulinumtoxinA (Botox®; Allergan, Inc.), in addition to nonoral systemic medications.

Topics: Acetanilides; Behavior Therapy; Botulinum Toxins, Type A; Catheter Ablation; Catheterization; Electric Stimulation Therapy; Exercise Therapy; Female; Humans; Neuromuscular Agents; Physical Therapy Modalities; Stem Cell Transplantation; Suburethral Slings; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence, Stress; Urologic Surgical Procedures

Mirabegron is being developed as a new treatment for the management of overactive bladder (OAB). It is an orally active drug that works by activating the β(3)-adrenoceptor with a better safety profile than antimuscarinic drugs. However, long-term adverse effects are not yet completely investigated.. The following article reviews the pharmacology and efficacy of mirabegron by analyzing the tolerability findings in the data available from several Phase II placebo-controlled clinical trials conducted with an active comparator. We aim to provide familiarity with the metabolic pathway responsible for disposition of mirabegron which makes it likely to produce pharmacokinetic interactions with other drugs, as although mirabegron is generally well tolerated, its potential to cause drug interactions may limit its use in some patients.. Mirabegron is a β(3)-adrenoceptor agonist developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile for OAB patients with advanced age and cognitive deficit. It has been well tolerated with significant efficacy in reducing the number of incontinence episodes and mean micturition frequency. The most commonly reported toxic effects of mirabegron are gastrointestinal adverse events and headache.

Topics: Acetanilides; Administration, Oral; Adrenergic beta-3 Receptor Agonists; Animals; Clinical Trials, Phase II as Topic; Drug Interactions; Humans; Thiazoles; Urinary Bladder, Overactive

Mirabegron (YM-178), currently in development by Astellas Pharma Inc, is an orally active β₃-adrenoceptor (AR) agonist for the potential symptomatic treatment of overactive bladder (OAB). Mirabegron demonstrates nanomolar EC50 values against the human β₃-AR in biochemical assays with potent selectivity over the β₁- and β₂-ARs. Originally developed as a treatment for diabetes, the development of mirabegron was later refocused to OAB. Cystometric experiments in rats reported a reduction in resting intravesical pressure and contraction frequency in anesthetized rats, without any effect on the amplitude of micturition contraction. Mirabegron also reduced non-micturition bladder contractions in an awake rat model of bladder outlet obstruction. Top-line results from clinical trials to date indicate that mirabegron has been well tolerated with significant efficacy in reducing the number of incontinence episodes and mean micturition frequency in patients. Evidence of cytochrome P450 (CYP)2D6 inhibition in clinical trials highlighted a concern for pharmacokinetic interaction with other drugs that are CYP2D6 substrates, as confirmed by a rise in the pharmacokinetic parameters of desipramine with concomitant administration of mirabegron. Mirabegron exhibits a novel mode of action in targeting the β₃-AR for bladder relaxation, and the studies and trials conducted to date suggest mirabegron as a promising new treatment in the management of OAB symptoms, such as increased urinary urgency and frequency, and urgency incontinence.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Rats; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urination Disorders

We aimed to determine whether the presence of metabolic syndrome (MS) affects the efficacy of mirabegron in treatment-naïve women with overactive bladder (OAB).. Women being treated with mirabegron 50 mg were allocated to MS and non-MS groups, and the efficacy of treatment of OAB was compared using the OAB symptom score (OABSS) and a 3-day voiding diary before and 12 weeks after starting treatment. The Wilcoxon signed-rank and Mann-Whitney U tests and multivariate logistic regression were used for statistical analyses, and a p-value < 0.05 was considered to represent statistical significance.. Of the 197 patients who completed the trial, 43 (23.9%) had MS. After 12 weeks of mirabegron treatment, both the MS and non-MS groups showed significant improvements in OABSS score, the number of incontinence episodes/24 h, the number of micturition episodes/24 h, and the number of episodes of urgency/24 h. The factors associated with clinically important differences in OABSS were the presence of hyperglycemia (odds ratio 2.43, 95% confidence interval [CI] 1.05-5.60) and OABSS score at baseline (odds ratio 1.23, 95% CI 1.09-1.39).. Mirabegron is effective in patients with and without MS, and comorbid hyperglycemia and severe OAB symptoms before treatment are predictors of the efficacy of mirabegron treatment.

Topics: Acetanilides; Female; Humans; Metabolic Syndrome; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To compare the efficacy and safety of mirabegron versus vibegron in postmenopausal women with treatment-naïve overactive bladder (OAB).. We conducted a prospective randomized controlled study of women with treatment-naïve OAB. The patients received mirabegron or vibegron at 50 mg daily for 12 weeks by a stratified randomized method. The OAB symptom score (OABSS) and quality of life (QOL) index were evaluated before and 4 and 12 weeks after the treatment. The patients' 3-day voiding diary and postvoided residual urine volumes were evaluated before and 12 weeks after the treatment.. Of 213 patients initially enrolled in this study, 199 patients were randomized to the mirabegron group (n = 97) or vibegron group (n = 102). Twelve weeks after the treatment, OABSS, QOL index, the numbers of micturition, urgency episodes, incontinence episodes, and voided volume per 24 hours were significantly improved compared with the baseline in both groups, and there was no significant difference in the rate of change in both groups. The postvoid residual urine volume was not significantly different in the 2 groups at 12 weeks. Discontinuation because of adverse effects was observed in 6.2% of patients in the mirabegron group and 6.8% in the vibegron group, with no significant difference between 2 groups.. Both mirabegron at 50 mg and vibegron at 50 mg improved OAB symptoms and the parameters of voiding diary equally in postmenopausal women with treatment naïve OAB.

Topics: Acetanilides; Aged; Aged, 80 and over; Female; Humans; Middle Aged; Prospective Studies; Pyrimidinones; Pyrrolidines; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Urgency-type urinary incontinence affects one in four older community-dwelling women and overlaps with other common aging-associated health syndromes such as cognitive impairment, physical mobility impairment, and depression. Observational studies have raised concern about potentially higher rates of delirium and dementia in older adults taking anticholinergic bladder medications, but few prospective data are available to evaluate the effects of these and other pharmacologic treatments for urgency incontinence on cognition and other multisystem functional domains important to older women.. The TRIUMPH study is a randomized, double-blinded, 3-arm, parallel-group trial comparing the multisystem effects of anticholinergic versus beta-3-adrenergic agonist bladder therapy and versus no active bladder anti-spasmodic pharmacotherapy in older women with urgency incontinence. Women aged 60 years and older (target N = 270) who have chronic urgency-predominant urinary incontinence and either normal or mildly impaired cognition at baseline are recruited from the community by investigators based in northern California, USA. Participants are randomized in equal ratios to take identically encapsulated oral anticholinergic bladder therapy (in the form of tolterodine 2 mg extended release [ER]), oral beta-3 adrenergic agonist bladder therapy (mirabegron 25 mg ER), or placebo daily for 24 weeks, with the option of participant-directed dose titration (to tolterodine 4 mg ER, mirabegron 50 mg ER, or matching placebo daily). Participants also receive patient-oriented information and instructions about practicing first-line behavioral management strategies for incontinence. The primary outcome is change in composite cognitive function over 24 weeks assessed by a comprehensive battery of cognitive tests, with a secondary exploration of the persistence of change at 36 weeks. Secondary outcomes include changes over 24 and 36 weeks in domain-specific cognitive function; frequency, severity, and impact of urgency-associated urinary symptoms; physical function and balance; sleep quality and daytime sleepiness; psychological function; and bowel function.. The TRIUMPH trial addresses the need for rigorous evidence to guide counseling and decision-making for older women who are weighing the potential multisystem benefits and risks of pharmacologic treatments for urgency incontinence in order to preserve their day-to-day functioning, quality of life, and independence in older age.. ClinicalTrials.gov NCT05362292. Registered on May 5, 2022.

Topics: Adrenergic Agonists; Aged; Cholinergic Antagonists; Double-Blind Method; Female; Humans; Middle Aged; Multicenter Studies as Topic; Muscarinic Antagonists; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective β. This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence.. OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting. Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Adult; Cholinergic Antagonists; Double-Blind Method; Humans; Muscarinic Antagonists; Prospective Studies; Quality of Life; Treatment Outcome; Urinary Bladder, Overactive

This study aimed to assess the efficacy and safety of mirabegron compared with vibegron (both 50 mg once daily) in Japanese female patients with symptoms of overactive bladder (OAB).. This prospective, 12-week, two-arm, parallel-group, open-label randomized trial (UMIN000038288) was conducted at a single clinic from December 2019 to September 2022. The primary efficacy outcome measure was the change in mean total overactive bladder symptom scores (OABSSs) from baseline to end of treatment (EOT) (Week 12). The secondary efficacy outcome measures were changes in mean International Prostate Symptom Score from baseline to EOT, the ratio of patients who achieved a minimal clinically important change (MCIC) of total OABSS, and individual domains of the King's Health Questionnaire. Safety assessments, such as adverse events (AEs), postvoid residual volume, and patient-reported incidences, were recorded at every visit.. There was no statistically significant adjusted mean difference between mirabegron and vibegron in terms of the primary outcome of the mean change from baseline to EOT in the total OABSS. The difference in the percentage of patients in the mirabegron and vibegron groups achieving an MCIC on the total OABSS was not statistically significant but appeared to be clinically important. The incidence of treatment-related AEs was significantly higher for the vibegron group (38.5%) than the mirabegron group (19.1%) (p = .047).. These results showed that both drugs were effective in female OAB patients, with no significant differences in terms of efficacy. However, the safety of vibegron requires further investigation.

Topics: Acetanilides; Double-Blind Method; Female; Humans; Male; Prospective Studies; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

This study investigates the efficacy and adverse events of beta-3 agonists and antimuscarinic agents for managing overactive bladder syndrome in Sjogren syndrome.. Sjogren's syndrome patients with an Overactive Bladder Symptom Score (OABSS) >5 were enrolled and were randomly assigned to mirabegron 50 mg/day or solifenacin 5 mg/day. Patients were evaluated on the recruitment day and reassessed at Week 1, 2, 4, and 12. The study's primary endpoint was to have a significant change in OABSS at Week 12. The secondary endpoint was the adverse event and crossover rate.. A total of 41 patients were included in the final analysis, with 24 in the mirabegron group and 17 in the solifenacin group. The study's primary outcome was a change of the OABSS at Week 12. We found that both mirabegron and solifenacin significantly reduce patients' OABSS after 12 weeks of treatment. The evolution of the OABSS was -3.08 for mirabegron and -3.71 for solifenacin (p = .56). Six out of 17 patients from the solifenacin group crossed over to the mirabegron arm due to severe dry mouth or constipation, while none from the mirabegron arm crossed over to the solifenacin group. Sjogren's syndrome-related pain was also improved in the mirabegron group (4.96-1.67, p = .008) compared to the solifenacin group (4.39-3.4, p = .49).. Our study showed that mirabegron is equally effective as solifenacin in treating Sjogren's syndrome patients with overactive bladder. Mirabegron is superior to solifenacin in terms of treatment-related adverse events.

Topics: Acetanilides; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Sjogren's Syndrome; Solifenacin Succinate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To confirm if mirabegron 50 mg shows efficacy in women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence versus placebo.. Post-hoc analyses were carried out using pooled data from a Japanese phase IIb and a phase III study. The primary efficacy end-point was baseline to end-of-treatment change in the mean number of micturitions/24 h. The secondary end-points were changes in the mean voided volume/micturition, mean number of urgency and incontinence episodes/24 h, and mean number of nocturia episodes/night. Other end-points were quality of life and incontinence normalization rates.. Women with urgency urinary incontinence (placebo n  = 204, mirabegron n = 214) and mixed urinary incontinence (placebo n = 122, mirabegron n = 139) were included. Change in mean micturitions/24 h at end-of-treatment for mirabegron was statistically significant versus placebo in both populations; the effect size increased over time. For all secondary end-points, median changes for mirabegron were statistically significant versus placebo at end-of-treatment, except for nocturia for the urgency urinary incontinence population and urgency for the mixed urinary incontinence population. Mirabegron showed larger improvements versus placebo in all quality-of-life domains, except for general health perception in the urgency urinary incontinence population. Incontinence normalization rates for mirabegron were 47.2% and 49.6% in the urgency urinary incontinence and mixed urinary incontinence populations, respectively, versus 42.6% and 39.3% for placebo.. Mirabegron 50 mg significantly improved key overactive bladder symptoms versus placebo in women with urgency urinary incontinence, and it also improved most overactive bladder symptoms, including micturition frequency, in patients with mixed urinary incontinence. These findings support the benefits of using mirabegron in the female overactive bladder wet population.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Double-Blind Method; Female; Humans; Japan; Muscarinic Antagonists; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To assess the safety and effectiveness of mirabegron in patients with PD complaining of overactive bladder (OAB).. From January 2017 to November 2020, we performed a prospective randomized, double-blind, placebo-controlled trial that enrolled PD patients with symptoms of OAB. The total duration of the study was 13 weeks, comprising a 1-week screening period and a 12-week treatment period. A total of 110 patients were randomized in one of two groups: treatment group (mirabegron 50 mg) or placebo group. The primary outcomes of our study were the change from baseline in OAB symptom score (OABSS) and the overactive bladder questionnaire short form (OAB-q SF) score. The secondary outcomes were the change from baseline in the mean number of micturitions/24 hours, the mean number of urgency episodes/24 hours, the mean number of urgency incontinence episodes/24 hours and the mean number of nocturia episodes/night, volume voided/micturition (ml) as recorded on a 3-day bladder diary. Safety assessments included adverse events, electrocardiogram, QT corrected for heart rate using Fridericia's correction (QTcF) interval and blood pressure and pulse rate measurements.. There was a significant improvement in the primary outcome and secondary outcome measures in the treatment group compared to the placebo group. Adverse events were mild and the same in the two groups. The cardiovascular safety profile was high. This study is limited by its sample size and its short follow-up period.. Mirabegron is a promising drug to control OAB symptoms in patients with PD with an excellent safety profile.

Topics: Acetanilides; Double-Blind Method; Humans; Parkinson Disease; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

This cohort study evaluates therapeutic efficacy and adverse events (AEs) of various overactive bladder (OAB) medications for patients with central nervous system (CNS) disorders.. Patients with OAB and CNS disorders were prospectively enrolled. They were randomly allocated to 3 different treatment subgroups: (1) mirabegron 50 mg once daily (2) solifenacin 5 mg per day, and (3) combined solifenacin 5 mg and mirabegron 50 mg once daily. Efficacy and safety questionnaires and objective parameters were compared among the subgroups, and subgroups between baseline and 3 and 6 months after treatment. AEs, including cognitive dysfunction, were assessed using the Mini-Mental State Examination (MMSE).. 102 patients (mean age, 71.8 ± 8.7 years) were enrolled, including 35, 36, and 31 patients received mirabegron monotherapy, solifenacin monotherapy, and combination therapy, respectively. OAB symptoms scores all significantly improved 3 months after treatment in different subgroup. However, PVR increased and VE decreased significantly after treatment in patients receiving solifenacin monotherapy and combination therapy. Dry mouth and constipation were the most common AEs, especially in the solifenacin and combination subgroups. Mild incidence of AEs was noted in patients receiving mirabegron monotherapy. No significant change in MMSE was noted among the subgroups after treatment.. OAB medication had good therapeutic efficacy in patients who had OAB with CNS disorders, especially in cerebrovascular accident and parkinsonism. No OAB medication or their combination affected cognitive function, whereas minimal AEs were noted with mirabegron. Mirabegron could be recommended as the first choice for managing OAB in these patients.

Topics: Acetanilides; Aged; Aged, 80 and over; Central Nervous System Diseases; Cognition; Cohort Studies; Drug Therapy, Combination; Humans; Middle Aged; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

The study aims to elucidate the impact of mirabegron versus solifenacin on autonomic function and peripheral arterial conditions in women with overactive bladder syndrome (OAB). All consecutive women with OAB were randomized to receive 12 weeks of mirabegron 25 mg or solifenacin 5 mg once per day. Heart rate variability, cardio-ankle vascular index, ankle-brachial pressure index, blood pressure, and heart rate were compared between the two groups. There were 87 women (mirabegron, n = 43; and solifenacin, n = 44) who completed 12-week treatment and underwent heart rate variability examination. Systolic blood pressure (median: - 4.5 to - 5.5 mmHg) and diastolic blood pressure (median: - 0.5 to - 3.5 mmHg) decreased after solifenacin treatment, and heart rate (median: + 2 bpm) increased after mirabegron treatment, despite of no between-group difference. In addition, posttreatment heart rate variability, cardio-ankle vascular index, and ankle-brachial pressure index did not differ compared with baseline; and there were no between-group differences. In conclusion, solifenacin might decrease blood pressure, and mirabegron might increase heart rate. Nonetheless, there were no significant impacts of 12-week mirabegron versus solifenacin treatment on autonomic function and arterial stiffness.

Topics: Acetanilides; Female; Humans; Muscarinic Antagonists; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents; Vascular Stiffness

To observe the efficacy and safety of solifenacin and/or mirabegron as a medical expulsive therapy (MET) in patients with double-J stent-related overactive bladder (OAB) symptoms. A total of 219 patients with double-J stent-related OAB symptoms were prospectively randomized into two groups. One-hundred and nine cases in the combination group accepted mirabegron and solifenacin therapy and 110 cases as control only accepted solifenacin therapy. The lower urinary tract symptoms and overactive bladder questionnaire (OAB-q) health-related quality of life (HRQol) and symptom bother score between two groups were compared at the 1st, 2nd and 4th week ends. All of 219 patients were randomly assigned to two groups, of which 109 patients were included in the combination group and 110 in the solifenacin group. The incidences of LUTS, including urgency, frequent urination, and incontinence episodes, in the 2nd week (44.9% vs. 64.5%, P = 0.028; 48.6% vs. 62.7%, P = 0.036; and 40.4% vs. 56.4%, P = 0.018) and the 4th week (14.7% vs. 30.9%, P = 0.004; 16.5% vs. 33.6%, P = 0.003; and 11.9% vs. 26.4%, P = 0.007) after combination treatment were significantly lower than those in the solifenacin group. The incidence of drug-related adverse events in the solifenacin group was higher than that in the combination group, but there was no statistically significant difference (P > 0.05). In terms of secondary variables, the OAB-q HRQol score in the combination group was statistically superior in comparison with that in the solifenacin group between the second and fourth week (77.9 vs. 76.4, P = 0.020; and 87.9 vs. 85.6, P = 0.001). The OAB-q symptom bother score was higher in the solifenacin group than in the combination group (37.6 vs. 36.4, P = 0.016; and 26.2 vs. 24.8, P = 0.003). Combination therapy of solifenacin and mirabegron demonstrated significant improvements over solifenacin monotherapy in reducing OAB symptoms associated with double-J stents, and providing a higher quality of life without increasing bothersome adverse effects.

Topics: Acetanilides; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Prospective Studies; Quality of Life; Solifenacin Succinate; Stents; Treatment Outcome; Urinary Bladder, Overactive

To evaluate the neurological safety and clinical efficacy of darifenacin and mirabegron in patients with a history of cerebrovascular accident (CVA) who had overactive bladder (OAB) symptoms.. This prospective randomized study, approved by the institute's ethics committee, was carried out at a tertiary care center from December 2018 to June 2020. Treatment naïve adult patients with a past history of CVA with stable neurological status for atleast past 3 months with symptoms of OAB for 3 or more months were included. Eligible patients received either darifenacin or mirabegron for a period of 3 months and various parameters on the 3-day International Consultation on Incontinence Questionnaire (ICIQ) bladder diary, the Montreal Cognitive Assessment-Basic score (MoCA-B), and the adverse events at 3 months posttreatment were compared to that at the baseline.. A total of 60 patients were included, 30 in each arm. After 3 months of treatment with darifenacin or mirabegron, the majority of the ICIQ bladder diary parameters improved and there was no deterioration in the cognitive function as noted on the MoCA-B score in either of the arms. On intergroup comparison, the mean change in bladder diary parameters and the MoCA-B scores was similar between the two groups.. Darifenacin and mirabegron, in the short term, do not adversely affect the cognitive function in patients with a history of CVA with OAB symptoms. Both are safe and effective treatment options in patients with OAB post-CVA.

Topics: Acetanilides; Adult; Benzofurans; Humans; Prospective Studies; Pyrrolidines; Stroke; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

This study aims to explore the efficacy and safety of mirabegron in treating irritative symptoms induced by intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) after transurethral resection of bladder tumors (TURBT).. A total of 160 patients subjected to TURBT was randomly divided into the mirabegron group and placebo group with 80 patients in each group. Then, the patients were administered 25 mg mirabegron or placebo daily, starting the first day after BCG infusion. The first BCG perfusion was conducted at least 2 weeks after TURBT. The 3-day bladder diaries were completed in all patients, 1 day before BCG perfusion, and on the 1st, 6th, and 13th days after the first BCG perfusion. Overactive bladder symptom scores were completed 1 day before BCG perfusion, and on the 6th and 13th days after the first BCG perfusion.. Symptom scores of bladder hyperactivity were significantly different between the two groups (p < 0.001). Also, the frequency of nocturia, pollakiuria, micturition urgency, urinary incontinence and was significantly lower in group 1 than that in group two (p < 0.05).. Our findings demonstrate that mirabegron is a valuable clinical drug for the management of irritative symptoms after TURBT with subsequent intravesical BCG perfusion.

Topics: Acetanilides; Aged; BCG Vaccine; Cystectomy; Double-Blind Method; Female; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Thiazoles; Urinary Bladder Neoplasms; Urinary Bladder, Overactive; Urological Agents

To investigate the efficacy and safety of mirabegron versus solifenacin as add-on for persistent OAB symptoms after tamsulosin monotherapy in men with probable BPO.. This prospective randomized single-blind study was conducted on patients with persistent OAB symptoms after at least 12 weeks of tamsulosin 0.4 mg. The patients were randomized into group A in which mirabegron (50 mg once daily) was added and group B in which solifenacin (5 mg once daily) was added. Before and 12 weeks after addition of either drugs, we assessed the efficacy of the treatment using the OABSS, IPSS, Q max, MVV/mic and PVR.. Ninety two men were included in this study (46 patients in each group). All the study parameters were significantly improved after the 12-week treatment period in both groups except mean PVR which showed non-significant change in group A and a significant change in group B despite of being clinically irrelevant with only one case of acute urine retention. Overall, no significant difference has been observed between both groups after 12 weeks of treatment regarding all studied parameters except PVR. The incidence of side effects in group A was 10.9% versus 26.1% in group B. Main side effects included dry mouth in 2.2% and 8.7% and constipation in 2.2% and 6.5% in group A and B, respectively.. Our results indicate that the addition of either mirabegron or solifenacin to patients with persistent OAB symptoms after tamsulosin monotherapy has significant efficacy in controlling these symptoms. The adequate balance between efficacy and tolerability reported in this study with mirabegron may result in better QOL and overall patient satisfaction if compared with antimuscarinics.

Topics: Acetanilides; Humans; Male; Middle Aged; Prospective Studies; Prostatic Hyperplasia; Single-Blind Method; Solifenacin Succinate; Tamsulosin; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

To investigate the cardiovascular safety of mirabegron add-on treatment to tamsulosin in male patients with residual overactive bladder symptoms.. This was a post hoc analysis of MATCH, the first double-blind, placebo-controlled study comparing mirabegron and placebo as add-on therapy to tamsulosin for treatment of overactive bladder in men with lower urinary tract symptoms. The analysis focused on treatment-emergent adverse events relating to the cardiovascular system or blood pressure, and changes in vital signs during 12 weeks of follow-up.. Cardiovascular-related treatment-emergent adverse events were reported by 6/566 patients, although only one serious treatment-emergent adverse event was related to treatment (unstable angina in the tamsulosin + placebo group). Hypertension (two patients) and increased blood pressure (one patient) were reported in the tamsulosin + placebo group, but there were no blood pressure-related treatment-emergent adverse events among tamsulosin + mirabegron patients. There were no clinically meaningful changes from baseline in blood pressure, and changes in pulse rate were small (+1.2 bpm in the tamsulosin + mirabegron group). Increased pulse rate was more frequent with tamsulosin + mirabegron than with tamsulosin + placebo in older patients, although within the normal range.. Cardiovascular-related adverse events were uncommon in both treatment groups. Mirabegron is a well-tolerated add-on therapy to tamsulosin in Japanese and Korean males with residual overactive bladder symptoms.

Topics: Acetanilides; Age Factors; Aged; Cardiovascular Diseases; Double-Blind Method; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Middle Aged; Tamsulosin; Thiazoles; Urinary Bladder, Overactive

To analyze the safety of mirabegron add-on therapy in men with overactive bladder symptoms concurrently receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia.. The Phase 4 PLUS study comprised a 4-week run-in period (tamsulosin [0.4 mg]) and a 12-week randomized treatment period (add-on treatment: mirabegron [25 mg] or placebo). Doses were increased to mirabegron 50 mg or matched placebo after 4 weeks. Safety assessments: treatment-emergent adverse events (TEAEs), vital signs, 12-lead electrocardiograms, and changes in postvoid residual volume and maximum urinary flow (Q. The safety analysis set included 352 tamsulosin plus mirabegron (TAM + MIRA) and 354 tamsulosin plus placebo (TAM + PL) patients. The frequency of overall TEAEs was higher with TAM + PL, although a higher incidence of drug-related TEAEs was observed with TAM + MIRA. Most TEAEs were mild or moderate in severity. Drug-related serious TEAEs were reported for 3 patients (2 TAM + MIRA patients: acute myocardial infarction with cerebral infarction and angina pectoris, 1 TAM + PL patient: lacunar stroke). Hypertension, headache, and nasopharyngitis were the most common TEAEs. Special interest TEAEs were infrequently reported. The most common was urinary retention and 2 TAM + MIRA patients required catheterization (neither led to discontinuation). No major changes in blood pressure or pulse rate were noted and similar electrocardiogram parameters were observed for both groups. Changes in mean postvoid residual volume and Q. No unexpected safety concerns were noted in men receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia who subsequently received mirabegron add-on therapy.

Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Double-Blind Method; Humans; Lower Urinary Tract Symptoms; Male; Middle Aged; Prostatic Hyperplasia; Tamsulosin; Thiazoles; Urinary Bladder, Overactive

MATCH was a randomized, double-blind, placebo-controlled study enrolling Japanese and Korean men aged ≥ 40 years who still had overactive bladder (OAB) symptoms while receiving tamsulosin. After a 4-week single-blind screening period in which patients received placebo and tamsulosin, patients were randomized to mirabegron 50 mg + tamsulosin or placebo + tamsulosin for 12 weeks (n = 568). This post hoc analysis investigated the proportion of treatment responders for each treatment group and for subgroups stratified by age based on voiding diaries and patient-reported outcomes (PROs).. Responders were defined as those achieving normalization or clinically meaningful improvements in efficacy, or clinically important differences in PROs [≥ 10-point improvement in OAB questionnaire (OAB-q) symptom bother or total health-related quality of life (HRQoL) subscales at end of treatment (EoT; minimally important difference [MID]) or OAB symptom score (OABSS) total score decreased by ≥ 3 points at EoT [minimally clinically important change (MCIC)]].. At EoT, micturition frequency normalization was achieved by 30.7% of tamsulosin + mirabegron patients and 18.6% of tamsulosin + placebo patients. Normalization of urgency and incontinence was 19.1% and 60.7% for tamsulosin + mirabegron and 18.2% and 60.0% for tamsulosin + placebo. Normalization of OAB symptoms based on OABSS was 17.1% for tamsulosin + mirabegron and 14.5% for tamsulosin + placebo. Higher proportions of patients in the mirabegron add-on group versus the placebo group reported clinically meaningful improvements in micturitions, urgency, and incontinence and in MCIC for OABSS and MID for the OAB-q subscales. Double- and triple-responder findings were as predicted by the results of single-responder analyses. These results were mirrored in the age groups using cut-offs of 65 and 75 years.. Mirabegron therapy added on to tamsulosin resulted in a higher frequency of responders in terms of normalization (e.g., micturition frequency normalization), clinically meaningful improvements in efficacy (e.g., ≥ 50% decrease in urgency), and minimally important changes in PROs (e.g., MCIC in OABSS).. ClinicalTrials.gov identifier, NCT02656173.

Topics: Acetanilides; Aged; Double-Blind Method; Drug Therapy, Combination; Humans; Male; Muscarinic Antagonists; Quality of Life; Single-Blind Method; Tamsulosin; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

This study aimed to investigate the efficacy and safety of mirabegron for Parkinsonism patients with overactive bladder (OAB) symptoms in a randomized, placebo-controlled, multicenter study.. Inclusion criteria are Parkinsonism with OAB symptoms for 4 weeks or more, OAB symptom score (OABSS) questionnaire scores greater than 2, and OABSS urgency question scores greater than 1. After a 2-week wash-out period, the patients were randomized into placebo and mirabegron groups at visit 2. Visit 3 was performed after 4 weeks of medication. Mirabegron was prescribed to the two groups for the rest of the study period at visit 4.. The mean age was 68.1 ± 8.1 years and 72 males and 64 females were included. A total of 136 patients were screened, 117 patients were randomized, and 25 patients dropped out. The OABSS scores were significantly different between the two groups at Weeks 4 and 8. The OABSS scores became the same in the two groups at Week 12 (visit 5). The postvoid residual urine volume showed a mild increase to 64 ml in the mirabegron group compared to the placebo group at visit 4. Adverse events occurred in 27 patients (23.1%). The degree was mild in 26 cases (78.8%), moderate in five (15.2%), and severe in two (6.1%). Only 13 cases (39.4%) showed medication-related adverse events. Acute urinary retention occurred in a single case. The treatment satisfaction questionnaires showed no significant differences between the two groups.. Mirabegron was effective in treating OAB symptoms in patients with Parkinsonism with acceptable adverse events.

Topics: Acetanilides; Aged; Double-Blind Method; Female; Humans; Male; Parkinson Disease; Surveys and Questionnaires; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To analyze cardiovascular safety of mirabegron in patients with spinal cord injury (SCI)- and multiple sclerosis (MS)-induced neurogenic detrusor overactivity (NDO) in a prospective, randomized, double-blind, placebo-controlled study.. Seventy-eight patients were enrolled into the study, and 66 of them were included into the final analysis. In 49 (74.2%), NDO developed due to suprasacral SCI, 17 (25.8%) suffered from NDO due to MS. Eleven patients were previously treated for hypertension and one for arrhythmia. All study participants received placebo for 2 weeks run-in period. Subsequently, eligible subjects were randomized for 4 weeks of active treatment with mirabegron 50 mg once daily (Group A; n = 32) or placebo (Group B; n = 34). Data from resting electrocardiography (ECG), 24-h ECG and blood pressure monitoring, and echocardiographic examination, were used for cardiovascular safety assessment. All reported variables were evaluated at time of randomization and at the end of the study. Longitudinal changes of variables within the groups and differences between the groups were assessed using nonparametric Kruskal-Wallis test, and p ≤ 0.05 was considered statistically significant.. No statistically significant longitudinal changes were found in safety variables, except for prolongation of QT interval in placebo group (p = 0.0328) recorded by resting ECG. No significant difference between the Groups A and B, in any of the variables, was observed. A single cardiovascular study drug-related adverse event was recorded in a patient with cervical SCI (3.13%).. Our results suggest that mirabegron can be safely used in the treatment of patients with SCI- and MS-induced NDO.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Cardiovascular Diseases; Double-Blind Method; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Prospective Studies; Spinal Cord Injuries; Thiazoles; Urinary Bladder, Overactive; Young Adult

The efficacy and safety of βeta-3 agonists (Mirabegron 50 mg) have been sparingly assessed in the published English literature. We aim to do an efficacy-safety analysis of Mirabegron-Tamsulosin combination therapy vs tamsulosin-placebo monotherapy in a select subset of medication virgin Benign Prostatic Enlargement (BPE) patients with coexisting predominant non-neurogenic overactive bladder symptoms (OABS).. After prior written informed consent and IEC, 80 patients of uncomplicated BPE with coexisting non-neurogenic OABS and IPSS of >7 without contraindications to drug therapy were computer randomised/allocated to receive either[50 mg Mirabegron plus Tamsulosin 0.4 mg (Intervention arm-I)]or [Tamsulosin 0.4 mg plus capsule lactobacillus (Comparator arm-II)] once daily for 8 weeks. Efficacy was evaluated using the OABS Score (OABSS), mean change in nocturnal frequency (NF), PVR and IPSS, while safety was assessed by recording treatment emergent adverse events (TEAE). Follow-up visits were performed at second, fourth and eighth week.. Patient data in both groups were generally comparable with the exception of NF and IPSS storage sub score (IPSS-ss). Significant improvements were visualised in the eighth week primary endpoint total OABS sub score (OABSS-ss) in the combination group (P < .001).Similar significant improvements were seen with most secondary parameters such as the mean change in NF, IPSS, IPSS-ss, OABS-ss, voided volume, Qmax, and Quality of life index (QOL) (P < .001). No significant increase in PVR was observed in the Mirabegron arm and no patient developed urinary retention. The TEAE were minor, self-limiting and managed symptomatically without drug discontinuity.. Mirabegron can be significantly efficacious and safe in ameliorating non-neurogenic OABS induced by BPE vs placebo by initiating combination therapy from the start as opposed to the usual 'add on therapy' protocol. This combination appeared to be superior in terms of overall safety, minimal side effects, better compliance and tolerability vs Tamsulosin monotherapy in select BPE patients with predominant non-neurogenic OABS.

Topics: Acetanilides; Drug Therapy, Combination; Humans; Male; Prostatic Hyperplasia; Quality of Life; Tamsulosin; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

To investigate whether adding an anticholinergic or beta-3 agonist can improve the therapeutic effect of intravesical onabotuliumtoxinA injection in patients with refractory overactive bladder (OAB).. Ninety OAB patients who received an intravesical 100-U onabotulinumtoxinA injection 1 month previously were consecutively invited into a prospective, randomized, open-label study. They were randomly adding on solifenacin 5 mg daily (QD) (30 patients), mirabegron 50 mg QD (31 patients), or no medication (29 patients, control). All enrolled patients completed a 3-day voiding diary, Overactive Bladder Symptom Score (OABSS) and Urgency Severity Scale (USS) questionnaires, Global Response Assessment (GRA) scale, and uroflowmetry at baseline (1 month after intravesical onabotulinumtoxinA injection) and 3-, 6-, 9-, and 12-month follow-up. The primary end point was the effective therapeutic outcome defined as no OAB wet during the 12-month period. The secondary end point included changes of GRA, OABSS, and the parameters of the voiding diary at 3 months.. The baseline data were comparable among the three groups. The percentage of OAB wet in the mirabegron-added-on group was significantly less than that in the solifenacin-added-on and onabotulinumtoxinA-only groups at four different time points (P = .02). At 3 months, the changes of GRA, OABSS, USS, urge urinary incontinence, frequency, nocturia episodes, and functional bladder capacity in the mirabegron-added-on group were significantly greater than those in the other groups. No serious adverse events were reported.. Adding mirabegron could increase the therapeutic effects, mainly on OAB symptoms and GRA scale, after intravesical onabotulinumtoxinA injection in refractory OAB patients.

Topics: Acetanilides; Botulinum Toxins, Type A; Humans; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

The purpose of this study is to investigate the efficacy and safety of mirabegron versus solifenacin in the treatment of newly diagnosed overactive bladder (OAB) in children.. We conducted a prospective randomized controlled study on pediatric patients with newly diagnosed OAB. Patients were randomized into 3 groups: mirabegron (50 mg once daily) in group I, solifenacin (5 mg) in group II, and placebo in group III. Before starting our treatment and at the end of the 3 months course, we obtained a 3-day voiding diary. This diary included incontinence episode per day, mean voided volume per micturition, mean number of micturition per day, and post-void residual urine. Moreover, the parents/patients were asked to rate symptom relief, and the adverse events were recorded throughout the study period.. A total of 190 patients aged from 5 to 14 years completed this study. At the end of this trial, both groups I and II showed significant improvement versus placebo regarding our efficacy parameters with no significant difference between group I and II. The overall success rate based on assessment of symptom relief was significantly higher in the treated groups (87.5% in I and 90.2% in II) versus placebo (55.8%). Dry mouth was reported in 2.8, 10, and 0% and constipation in 2.8, 11.4, and 1.4% in group I, II, and III, respectively, without statistically significant difference between group I and placebo. However, there was a significant difference between group II and placebo regarding these side effects.. Both mirabegron and solifenacin have comparable efficacy regarding the control of OAB symptoms in the newly diagnosed children, but mirabegrone seems to have less side effects.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Age Factors; Child; Child, Preschool; Egypt; Female; Humans; Male; Muscarinic Antagonists; Prospective Studies; Single-Blind Method; Solifenacin Succinate; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics; Urological Agents

To investigate the effect of oxybutynin patch versus β3-adrenoceptor agonist mirabegron on nocturia-related quality of life in female overactive bladder patients.. In the present study, female overactive bladder patients were enrolled. The patients were randomly allocated into two groups: the oxybutynin patch group and the mirabegron group. Each of the drugs was given for 8 weeks. The changes in the total Nocturia Quality of Life Questionnaire score were evaluated. Parameters on a frequency volume chart were also evaluated.. In total, 100 patients (51 oxybutynin patch, 49 mirabegron) were treated with oxybutynin patch or mirabegron. The changes in the Nocturia Quality of Life Questionnaire score 4 weeks after administration were 3.8 ± 18.6 and 8.7 ± 13.1 with the oxybutynin patch group and the mirabegron group, respectively, which were significantly higher than those at the baseline. Furthermore, the changes in the Nocturia Quality of Life Questionnaire score 8 weeks after administration were 4.3 ± 16.5 and 7.7 ± 12.3, respectively. A statistical difference was seen only in the mirabegron group. Regarding the Nocturia Quality of Life Questionnaire subscores, oxybutynin patch and mirabegron significantly improved the Nocturia Quality of Life Questionnaire bother/concern subscore 4 and 8 weeks after administration, whereas the Nocturia Quality of Life Questionnaire sleep/energy subscore was not significantly improved in each period. Eight weeks after administration, 24-h frequency, 24-h urinary urgency and mean voided urine volume were improved in both groups statistically.. The oxybutynin patch improves quality of life, focusing mainly on nocturia by improving the bother/concern subscores of the Nocturia Quality of Life Questionnaire in the short term.

Topics: Acetanilides; Double-Blind Method; Female; Humans; Mandelic Acids; Nocturia; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Aged; Aged, 80 and over; Benzhydryl Compounds; Humans; Indoles; Lower Urinary Tract Symptoms; Male; Middle Aged; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

This analysis was conducted to investigate the cardiovascular (CV) safety outcomes from the MILAI II study. MILAI II was conducted to evaluate the long-term safety and efficacy of antimuscarinic add-on therapy to mirabegron over 52 weeks in patients with overactive bladder (OAB) symptoms.. MILAI II consisted of a 2-week screening period (patients received mirabegron 50 mg once daily) plus a 52-week treatment period (patients were randomized to receive a combination of mirabegron 50 mg/d plus solifenacin 5 mg/d, propiverine 20 mg/d, imidafenacin 0.2 mg/d, or tolterodine 4 mg/d). CV safety was assessed using treatment-emergent adverse events (TEAEs), vital signs, and 12-lead electrocardiograms (ECGs). Vital signs and ECG data were evaluated for each patient using worst post-baseline values reported.. Of 647 patients, 570 (88.1%) were female with a mean age of 65 years. CV history at baseline and CV-related concomitant medication use throughout the study were balanced between groups. The incidences of overall and drug-related CV TEAEs were ≤8.1% and ≤6.2%, respectively, for all groups. The most common TEAEs were ECG T wave amplitude decreased, ECG QT prolonged, and ventricular extrasystoles. Overall, 36 TEAEs of interest related to the CV system that were possibly/probably related to treatment were reported with similar incidences for each group. For the worst post-baseline vital signs and ECGs, no relationships were noted in terms of either timing or treatment group.. A favorable CV safety profile was observed following long-term combination treatment with mirabegron and an antimuscarinic in patients with OAB symptoms.

Topics: Acetanilides; Aged; Aged, 80 and over; Benzilates; Cardiovascular Diseases; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Imidazoles; Japan; Male; Middle Aged; Muscarinic Antagonists; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Mirabegron, a β3-adrenoreceptor agonist, is an alternative drug to antimuscarinics for overactive bladder (OAB) symptoms.. To summarise safety and efficacy reporting of mirabegron treatment for OAB symptoms.. Pooled data analysed from 10 phase 2-4, double-blind, 12-wk mirabegron monotherapy studies in adults with OAB who had received one or more doses of study drug.. Mirabegron: 25 and 50mg; antimuscarinics: solifenacin (2.5, 5, and 10mg) and tolterodine extended release (4mg).. Baseline OAB-related characteristics, intrinsic and extrinsic factors, and analyses by age (<65 vs ≥65yr and <75 vs ≥75yr) and sex were assessed. Solifenacin 2.5 and 10mg groups were not included in the efficacy analyses (small patient numbers). Safety was evaluated using the proportion of treatment-emergent adverse events. Efficacy variables were derived from bladder diaries (baseline and week 12).. Baseline hypertension and diabetes were more frequent across treatment groups in the older versus younger age groups and in men versus women. Within sexes, frequencies were similar between treatment groups. Some differences were observed in baseline characteristics, including type of incontinence and medical history between sexes. No previously unreported safety concerns were identified. Improvements in efficacy (mean number of incontinence episodes/24h, micturitions/24h, urgency episodes/24h, volume voided/micturition, and nocturia episodes) versus placebo were observed in all treatment groups. Significant treatment-by-subgroup interactions included change from baseline in the mean number of incontinence episodes/24h by age (<65 vs ≥65yr), nocturia by age (<65 vs ≥65yr and <75 vs ≥75yr), and urgency episodes by previous OAB medication.. Data from this integrated database of 10 mirabegron studies reaffirm the safety and efficacy profiles of mirabegron, solifenacin, and tolterodine in adults of different age groups and sexes.. Overactive bladder is a complex of symptoms including a compelling desire to pass urine that leads to increased frequency, which may lead to a degree of incontinence if you do not reach the toilet in time and may wake you from sleep. We pooled data from 10 different studies of mirabegron in patients with overactive bladder symptoms, and looked at the effect in the total number of patients who received the treatment, as well as in different age groups and between men and women. No new safety concerns were identified, and mirabegron improved the symptoms of overactive bladder.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Databases, Factual; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Men with lower urinary tract symptoms (LUTS) treated with α-blockers (eg, tamsulosin) may experience overactive bladder (OAB) symptoms and receive add-on antimuscarinics. Mirabegron (a β3-adrenoreceptor agonist) is an alternative add-on therapy.. To evaluate the efficacy of mirabegron versus placebo in men with OAB symptoms receiving tamsulosin for LUTS.. Japanese and Korean men with OAB treated with tamsulosin for LUTS (January 2016-July 2017).. Single-blind, 4-wk screening: tamsulosin plus placebo orally once daily; double-blind, 12-wk treatment: patients randomized (n=568) to mirabegron 50mg or placebo, as add-on to tamsulosin.. Primary endpoint: baseline to end of treatment (EoT) change in the mean number of micturitions/24h, based on a 3-d voiding diary. Secondary endpoints: change in other diary variables and patient-reported outcomes from baseline to EoT. The primary endpoint was analyzed by analysis of covariance, including treatment group and region as fixed factors and baseline as a covariate.. Mirabegron add-on therapy was superior to placebo in improving the primary endpoint (adjusted mean difference [95% confidence interval] vs placebo -0.52 [-0.82 to -0.21]) and secondary endpoints, including mean volume voided/micturition (12.08 [6.33-17.84]), OAB symptom score (-0.65 [-1.04 to -0.26]), International Prostate Symptom Score total (-1.19 [-1.94 to -0.44]), storage (-0.78 [-1.13 to -0.43]), quality of life scores (-0.29 [-0.51 to -0.07]), OAB symptom bother (-4.52 [-6.91 to -2.13]), and total health-related quality of life (2.79 [1.13 to 4.44]). Differences, compared with placebo, in urgency, urgency urinary incontinence, and nocturia were not statistically significant. Mirabegron was well tolerated, with no major safety concerns. Limitations included a lack of antimuscarinic comparison.. The mirabegron add-on therapy to tamsulosin for 12 wk in men with LUTS and OAB symptoms demonstrated superior efficacy to placebo and was well tolerated.. We looked at the efficacy and safety of mirabegron compared with placebo in men being treated with tamsulosin but who still had overactive bladder symptoms. Mirabegron improved overactive bladder symptoms and patient-reported outcomes compared with placebo, and was well tolerated.

Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Aged; Double-Blind Method; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Middle Aged; Single-Blind Method; Tamsulosin; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

The majority of patients with overactive bladder (OAB) are aged >65yr. There has been no prospectively designed study assessing treatment efficacy with the β3-adrenoreceptor agonist, mirabegron, specifically in this age group.. A phase IV study comparing flexibly dosed mirabegron versus placebo in elderly patients with OAB and urgency incontinence.. Community-dwelling patients aged ≥65yr with OAB for ≥3mo.. Following a 2-wk placebo run in, patients with one or more incontinence episodes, three or more urgency episodes, and an average of eight or more micturitions/24h were randomised 1:1 to double-blind 25mg/d mirabegron or matched placebo, for 12wk. After week 4 or 8, the dose could be increased to 50mg/d mirabegron/matched placebo based on patient and investigator discretion.. Coprimary endpoints: change from baseline to end of treatment (EOT) in the mean numbers of micturitions/24h and incontinence episodes/24h. Secondary endpoints: change from baseline to EOT in the mean volume voided/micturition, mean number of urgency episodes/24h, and mean number of urgency incontinence episodes/24h. Analysis of covariance (ANCOVA) was used for the mean number of micturitions/24h, mean volume voided/micturition, and mean number of urgency episodes/24h. Stratified rank ANCOVA was used for the mean numbers of incontinence episodes/24h and urgency incontinence episodes/24h.. Statistically significant improvements were observed for mirabegron versus placebo in change from baseline to EOT in the mean number of micturitions/24h, mean number of incontinence episodes/24h, mean volume voided/micturition, mean number of urgency episodes/24h, and mean number of urgency incontinence episodes/24h. Safety and tolerability were consistent with the known mirabegron safety profile.. Mirabegron efficacy, safety, and tolerability over 12 wk were confirmed in patients aged ≥65yr with OAB and incontinence.. We examined the effect of mirabegron compared with placebo in people aged 65yr or older with overactive bladder and incontinence. Mirabegron improved the symptoms of overactive bladder compared with placebo. Side effects were similar to those already known for mirabegron.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Double-Blind Method; Female; Humans; Male; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

PLUS investigated the efficacy and safety of mirabegron add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying lower urinary tract symptoms attributable to benign prostatic hyperplasia.. In this phase 4 study a 4-week 0.4 mg tamsulosin run-in period was followed by a 12-week, randomized, double-blind, treatment period in which patients initially received 25 mg mirabegron or placebo add-on therapy. At 4 weeks doses were titrated to 50 mg mirabegron or placebo equivalent. Efficacy end points were changes from baseline to end of treatment in mean number of micturitions per day (primary), mean volume voided per micturition, number of urgency episodes per day, total urgency and frequency score, and total International Prostate Symptom Score (secondary). Safety assessments included treatment emergent adverse events, and post-void residual volume, and maximum urinary flow measurements.. Of the 676 men most were 65 years old or older (380, 56.2%). Tamsulosin plus mirabegron was statistically superior to tamsulosin plus placebo in reducing the mean number of micturitions per day (-2.00 vs -1.62; adjusted difference -0.39; 95% CI -0.76, -0.02). Statistically superior results were noted for tamsulosin plus mirabegron in mean volume voided per micturition, urgency episodes per day, and total urgency and frequency score (not International Prostate Symptom Score). Higher overall treatment emergent adverse event rates were observed with tamsulosin plus placebo, although higher rates of drug related treatment emergent adverse events were noted with tamsulosin plus mirabegron. Urinary retention rates were higher in the tamsulosin plus mirabegron group. Post-void residual volume and maximum urinary flow results were not clinically meaningful.. The results of PLUS underscore the utility of mirabegron add-on therapy to treat men with overactive bladder symptoms receiving tamsulosin for benign prostatic hyperplasia.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Middle Aged; Prostatic Hyperplasia; Tamsulosin; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

 OBJECTIVES: The double-J (DJ) stents are commonly used to relieve the ureteral obstruction. Besides several known benefits, some of the patients encounter stent-related morbidities with considerable effects on the quality of life, general health situation, sexual matters, and daily work performance. In this study, we evaluated the effectiveness of tamsulosin/solifenacin combination and mirabegron in reducing DJ stent-related symptoms. MATERIALS AND METHODS: A total of 120 patients with 28cm 4.7fr DJ catheter inserted due to ureteral obstruction were included in this study. Patients were randomly divided into three groups of 40 each; group one received only oral hydration for six weeks; group two received 0.4 mg tamsulosin/10 mg solifenacin, and group three received 50 mg mirabegron. Preoperative and after 6 weeks, the VAPS, OAB-q index, and IPSSs forms were filled. RESULTS: The mean age of the patients was 41.60 ± 12.34 years. There was no significant difference between the groups in terms of preoperative and postoperative VAPS values (p>0.05). There was a significant difference in postop IPSSs values (p:0.001). It was higher in the hydration group than tamsulosin/solifenacin and mirabegron groups. Postoperative IPSS value of the hydration group was 21.78 ± 2.54 while the tamsulosin/ solifenacin and mirabegron groups were 15.6 ± 4.37 and 13.65 ± 4.97, respectively. The use of mirabegron and tamsulosin/solifenacin combination alleviates the LUTSs related with DJ stent. There was also a significant difference between groups in terms of postoperative OAB-q values (p:0.001). Postoperative OAB-q values in the tamsulosin/solifenacin group were significantly higher than the mirabegron group. Postoperative OAB-q value of the hydration group was 29.95 ± 5.21, while the tamsulosin/solifenacin and mirabegron groups were 23.68 ± 4.07 and 18.15 ± 4.1, respectively. Our results also showed that, as a beta-3 adrenergic receptor agonist, mirabegron can improve the OAB-q scores. CONCLUSION: Tamsulosin and solifenacin combination is a significantly good treatment option for reducing LUTS associated with DJ stents. Mirabegron single therapy showed good results in treating LUTS and better results in treating OAB symptoms related with DJ stents than other therapies.. El catéter doble J se utiliza para desobstruir el uréter. A parte de los ya conocidos beneficios, algunos pacientes tienen efectos adversos derivados de llevar el catéter que empeoran su calidad de vida, su vida sexual, sus actividades laborales. En este estudio, evaluamos la efectividad de la tamsulosina/solifenacina en combinación y mirabegron en reducir estos síntomas.MATERIAL Y MÉTODOS: Un total de 120 pacientes con cateteres de 28cm/4.7 Ch fueron incluidos en el estudio. Los pacientes se randomizaron en 3 grupos, 40 en cada grupo (un grupo recibio hidratación oral durante 6 semanas, otro grupo tamsulosina 0,4 mg/10 mg solifenacina y el tercero 50 mg mirabegron). VAPS, OAB q index y IPSS cuestionarios se rellenaron en el preoperatorio y a las 6 semanas de tratamiento.. La mediana de edad fue de 41ª. No había diferencias significativas en los grupos en términos de valores VAPS preoperatorios y postoperatorios. Se evidenció una diferencia significativa en los valores IPSS (p=0,001), ya que fue mas elevado en el grupo de hidratación oral que el grupo de tamsulosina/solifenacina y mirabegron. El valor postoperatorio de IPSS en el grupo de hidratación fue de 22, mientras que en la tamsulosina y mirabegron fue de 15 y 13, respectivamente. El uso de mirabegron y tamsulosina mejora los síntomas tracto urinario inferior por el catéter. También se evidencio una diferencia significativa entre los grupos en términos de OAB-q (p=0,001). Los valores postoperatorios OAB-q en el grupo tamsulosina fueron mas altos que en el grupo mirabegron. El valor OAB-q postoperatorio en el grupo de hidratación oral fue de 29, tamsulosina 23 y mirabegron 18, respectivamente. Nuestros resultados también demuestran que mirabegron puede mejorar los resultados de OAB-q.. Tamsulosina/solifenacina es un buen tratamiento para mejorar los STUI asociados a catéteres. Mirabegon demuestra también buenos resultados en el tratamiento de los síntomas de vejiga hiperactiva relacionados en el catéter mejor que otras terapias.

Topics: Acetanilides; Adult; Drug Therapy, Combination; Humans; Middle Aged; Quality of Life; Solifenacin Succinate; Tamsulosin; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Catheters; Urological Agents

BACKGROUNDMirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTSChronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSIONThese findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease.TRIAL REGISTRATIONClinicaltrials.gov NCT03049462.FUNDINGThis work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).

Topics: Acetanilides; Adipose Tissue, Brown; Adolescent; Adult; Apolipoprotein A-I; Biomarkers; Cholesterol, HDL; Female; Humans; Insulin Resistance; Positron Emission Tomography Computed Tomography; Thiazoles; Urinary Bladder, Overactive

To evaluate efficacy and safety of combination of tadalafil + mirabegron for overactive bladder/benign prostatic hyperplasia (OAB/BPH).. Male patients with lower urinary tract symptoms (50 to 89 years), with remaining OAB symptoms even after administering tadalafil for more than 8 weeks were randomly assigned to either tadalafil monotherapy group (5 mg/day) or tadalafil/mirabegron combination therapy group (5 mg/50 mg/day). The primary endpoint was change from baseline in total OAB symptom score (OABSS) at week 12. The secondary endpoints were changes in International Prostate Symptom Score (IPSS), NIH-chronic prostatitis symptom index (NIH-CPSI), and micturition chart parameters at weeks 4 and 12.. A total of 176 patients were randomized to either monotherapy (87 patients) or combination therapy (89 patients). The baseline characteristics of patients in the two groups were similar. The total OABSS (95% confidence interval) of combination therapy was significantly decreased by 1.78 (1.05-2.50) points compared with that of monotherapy (P < .001). Changes from baseline in OABSS nighttime voiding score, urgency score, urgency incontinence score, IPSS storage subscores, NIH-CPSI total score, and numbers of voids, nighttime-voids, and urgency episodes/day in micturition chart were significantly reduced in combination therapy (all P < .001). Patient-reported outcome was significantly more satisfactory in combination therapy than in monotherapy (P < .001). One moderate adverse event (pain in hip joint) with hardly presumed causal relationship with therapy and seven mild adverse events were noted in monotherapy and combination therapy group, respectively.. The effect of tadalafil/mirabegron combination therapy on relieving OAB symptoms appeared to be greater than that of tadalafil monotherapy and can be safely used.

Topics: Acetanilides; Aged; Aged, 80 and over; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Middle Aged; Prostatic Hyperplasia; Tadalafil; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

Antimuscarinics are often used for treatment of overactive bladder (OAB), but exposure to medications such as antimuscarinics that have anticholinergic properties has been linked to adverse cognitive effects. A phase 4 placebo-controlled study (PILLAR; NCT02216214) described the efficacy and safety of mirabegron, a β. Outpatients aged ≥65 years with wet OAB were randomized 1:1 to mirabegron or placebo, stratified by age (<75/≥75 years). There were no exclusion criteria regarding cognitive status. Patients randomized to mirabegron initially received 25 mg/day with an optional increase to 50 mg/day after week 4/8 based on patient/investigator discretion. The MoCA was administered at baseline and end of treatment (EoT, week 12). The study protocol was Independent Ethics Committee/Institutional Review Board-approved.. Of the 887 randomized patients who received ≥1 dose of study drug, 72.3% were female, 79.5% were white, and 28.1% were aged ≥75 years. All patients had ≥1 comorbidity and 94.3% were receiving ≥1 concomitant medication. One third of patients had a history of psychiatric disorders, the most common being depression (17.2%), insomnia (15.7%), and anxiety (11.4%). Baseline mean (standard error, SE) MoCA total scores were 26.9 (0.1) and 26.8 (0.1) in the mirabegron and placebo groups, respectively. Among patients with MoCA data available at baseline/EoT, 27.1% (115/425) and 25.8% (106/411) of mirabegron and placebo group patients, respectively, had impaired cognitive function at baseline (MoCA total score <26). There was no statistically significant change in adjusted mean (SE) MoCA total score from baseline to EoT in the mirabegron group (-0.2 [0.1]) or the placebo group (-0.1 [0.1]).. Treatment with mirabegron for 12 weeks did not contribute to drug-related cognitive side effects in patients aged ≥65 years, as measured by the MoCA. Furthermore, the pattern of change in cognition over time in an older OAB trial population does not appear to differ from that of subjects receiving placebo.. NCT02216214 (prospectively registered August 13, 2014).

Topics: Acetanilides; Aged; Cognition; Female; Humans; Male; Mental Status and Dementia Tests; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

In older patients with overactive bladder (OAB), mirabegron, a β. Our objective was to further examine the safety and tolerability of mirabegron versus placebo treatment in patients aged ≥ 65 years with OAB-wet.. We conducted a 12-week, double-blind, randomized, placebo-controlled phase IV study to compare mirabegron with placebo. Community-dwelling patients aged ≥ 65 years with OAB-wet (one or more incontinence episode and three or more urgency episodes, and an average of eight or more micturitions/24 h over a 3-day diary) were randomized to receive placebo or mirabegron 25 mg/day (optional dose escalation to 50 mg/day at week 4 or 8). Safety analyses were performed for adverse events (AEs) and vital signs on all randomized patients who received one or more dose of study drug.. Treatment-emergent AEs (TEAEs), the majority mild or moderate in severity, were reported in 39.4% of placebo patients and 44.2 and 49.8% of those who received mirabegron 25 mg or 50 mg, respectively. The most common TEAEs in mirabegron-treated patients were urinary tract infection, headache, and diarrhea. The incidence of TEAEs was slightly higher in mirabegron patients aged ≥ 75 years than in those aged < 75 years. There were no clinically meaningful differences in changes in vital signs from baseline to end of treatment for any treatment group, and no differences were observed between mirabegron and placebo treatment groups. TEAEs tended to occur early post exposure and were not dose related.. Mirabegron treatment was well-tolerated in older adults with OAB-wet. Safety and tolerability were consistent with the known mirabegron safety profile.. This study is registered at ClinicalTrials.gov: NCT02216214.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Age Factors; Aged; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Female; Headache; Humans; Male; Middle Aged; Severity of Illness Index; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To determine the patient-perceived effectiveness and tolerability of mirabegron compared to solifenacin in a multiple sclerosis (MS) population with overactive bladder (OAB) symptoms.. MS patients with OAB symptoms who were not on medication for their urinary symptoms at enrollment were prospectively recruited. Patients enrolled in years 1-2 were prescribed mirabegron, whereas patients enrolled in years 3-4 were prescribed solifenacin. At enrollment and 6-week follow-up, patients completed several patient reported outcome measures. The primary outcome was change in OAB Questionnaire Short Form (OAB-q SF) symptom severity and minimal clinically important difference (MCID) achievement. The Patient Assessment of Constipation Symptoms (PAC-SYM) was used to assess bowel function over the treatment period.. Sixty-one patients were enrolled. The majority of the mirabegron (70%) and the solifenacin (69%) group achieved the OAB-q SF symptom severity MCID. The solifenacin group had a statistically significant greater decrease in its end of study OAB-q SF score (Δ = -37.87 vs -20.43, P = .02). Constipation improved in the mirabegron group and worsened in the solifenacin group (ΔPAC-SYM = -0.38 vs +0.22; P = .02), with 30% of patients prescribed solifenacin experiencing worsening above the MCID threshold.. Among MS patients, we demonstrated similar response rates to mirabegron and solifenacin, with approximately 50%-70% achieving each patient reported outcome measure's MCID. Though this small study showed some short-term evidence that improvement in urinary symptom severity was greater with solifenacin, this potential benefit must be weighed against the observed risk of worsening constipation. Further studies are needed to confirm these findings.

Topics: Acetanilides; Adult; Constipation; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Patient Reported Outcome Measures; Prospective Studies; Severity of Illness Index; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To assess the efficacy and safety of 2 drugs for overactive bladder (OAB), solifenacin and mirabegron. Fortyseven female OAB patients were randomized into 2 groups. Twenty-three patients were initially prescribed solifenacin for 4 weeks, followed by mirabegron for 4 weeks (group S). The other 24 patients were initially prescribed mirabegron for 4 weeks, followed by solifenacin for 4 weeks (group M). Evaluations included clinical determination of the OAB symptom score (OABSS), International Prostate Symptom Score (IPSS), and Visual Analog Scale. The IPSS significantly improved after the administration of solifenacin in both groups. The OABSS significantly improved in both groups after 4 weeks. In group M, the OABSS after eight weeks was significantly improved compared to that after 4 weeks. However, in group S, it was not significantly improved. Twelve patients experienced adverse events during the solifenacin treatment, while 2 patients experienced adverse events during the mirabegron treatment. Both solifenacin and mirabegron led to improved OAB symptoms. Switching from mirabegron to solifenacin significantly improved the OABSS. However, mirabegron led to fewer adverse events than solifenacin. We recommend that mirabegron be prescribed first for OAB patients. If patients are not satisfied with mirabegron, solifenacin should be used.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Cross-Over Studies; Female; Humans; Middle Aged; Prospective Studies; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive; Visual Analog Scale

A 12-week post-marketing study was conducted to provide real-world data on Japanese patients with overactive bladder (OAB) initiating treatment with mirabegron. This post-hoc analysis focused on safety and effectiveness of mirabegron in patients aged ≥75 versus <75 years.. Incidence of adverse drug reactions (ADR) was assessed following 12 weeks' mirabegron treatment. Overactive Bladder Symptom Score (OABSS) and International-Prostate Symptom Score Quality of Life (I-PSS QoL) were completed at baseline and at the end of treatment (EoT). A reduction of ≥3 points in total OABSS was defined as a minimal clinically important change (MCIC).. Of 9795 patients, a greater proportion aged ≥75 versus <75 years had a lower body mass index (BMI; BMI < 18.5: 4.2% vs 3.2%), longer OAB duration (≥3 years: 24.6% vs 20.3%) and more severe OAB symptoms (severe: 17.0% vs 11.2%). A significantly greater percentage of patients aged ≥75 versus <75 years had comorbidities (77.8% vs 66.0%) and used concomitant drugs (58.3% vs 48.7%; P < 0.001). Incidence of ADR was observed in 7.00% and 5.19% of patients aged ≥75 versus <75 years, respectively. At EoT, mirabegron treatment was reported 'effective' in 79.3% versus 82.1% of patients aged ≥75 versus <75 years, respectively. Mean total OABSS decreased significantly from baseline, and exceeded the MCIC in 61.0% and 65.9% of patients aged ≥75 and <75 years, respectively. Similar changes were observed for I-PSS QoL in both groups.. In a real-world clinical setting, mirabegron was well-tolerated and effective in patients aged ≥75 and <75 years.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Female; Humans; Male; Product Surveillance, Postmarketing; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To investigate the efficacy and safety of mirabegron dose escalation from 25 to 50 mg in Asian patients with overactive bladder (OAB).. A total of 242 patients (mean age: 67 years) with OAB were randomized to two groups: M25 (mirabegron 25 mg daily for 12 weeks) and M50 (mirabegron 25 mg daily for 4 weeks + 50 mg daily for 8 weeks). The primary endpoint was the percentage of patients without urgency or with a reduction of ≥2 in daily urgency episodes after treatment. Secondary endpoints included OAB symptom scores and other voiding parameters. Chi-squared and Wilcoxon signed-rank tests were used for data comparison.. All OAB symptom scores in both groups improved significantly at 4 and 12 weeks. Both groups showed similar numbers of patients who reached the primary endpoint after treatment (M25: 64.6%, 42/65; M50: 64.9%, 50/77; p = 0.554). Patients in the M50 group with residual daily urgency or urgency urinary incontinence (UUI) episodes after 4 weeks of mirabegron 25 mg had a significantly higher rate of reduction in daily urgency episodes (60.9% vs. 34.5%, p = 0.034) and daily UUI episodes (87.5% vs. 37.5%, p = 0.021). Adverse event (AE) rates were similar between the groups.. Mirabegron 25 mg for 12 weeks and mirabegron dose escalation from 25 to 50 mg exerted similar therapeutic effects. However, the dose escalation further improved the daily urgency and UUI episodes in patients with residual urgency or UUI after the initial treatment with mirabegron 25 mg.

Topics: Acetanilides; Aged; Aged, 80 and over; Double-Blind Method; Female; Humans; Male; Middle Aged; Taiwan; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

To evaluate the efficacy and safety of mirabegron in males with overactive bladder (OAB) symptoms.. In total, 464 males with OAB symptoms were enrolled from 14 institutes and were sorted into either the mirabegron 50 mg (n = 310) or placebo (n = 154) groups. The change in (i) the mean number of 24-h micturition episodes; (ii) OAB Symptom Scale (OABSS); and (iii) International Prostate Symptom Score (IPSS) from baseline to 12 weeks of treatment were compared between the two groups. Safety assessments included treatment-emergent adverse events, blood pressure, pulse rate, postvoid residual volume, and maximum urinary flow rate. After 12 weeks, the study was extended for 14 additional weeks by administering mirabegron 50 mg to both groups.. The reduction in the mean number of 24-h micturition episodes from baseline to 12 weeks of treatment was similar between the two groups. However, significantly greater changes from baseline to 12 weeks were observed in total OABSS, OABSS urgency incontinence score (Q4), IPSS storage subscore (Q2 + Q4 + Q7), and IPSS urgency score (Q4) in the mirabegron group (P = 0.01 for all). According to the extended study, the changes of all efficacy variables from baseline to 26 weeks were similar between both groups. The safety assessment results were also similar between the two groups at 12 and 26 weeks.. A daily 50 mg dose of mirabegron for 12 weeks reduced OAB symptoms in men, and no significant adverse events compared to the placebo group were noted.

Topics: Acetanilides; Aged; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urination; Urological Agents

To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron.. During a 2-week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks' treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment-emergent adverse events, vital signs, 12-lead electrocardiograms, post-void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night-time micturitions.. Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment-emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores.. Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Benzilates; Blood Pressure; Constipation; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Imidazoles; Japan; Male; Middle Aged; Muscarinic Antagonists; Nasopharyngitis; Severity of Illness Index; Solifenacin Succinate; Thiazoles; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Xerostomia

SYNERGY II was a 12-month phase III trial in patients with overactive bladder (OAB) symptoms that investigated the safety and efficacy of the combination of mirabegron and solifenacin in comparison with each monotherapy. This analysis evaluated the trial findings using four age subgroups (<65, ≥65, <75, and ≥75 years).. Eligible patients were ≥18 years with symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for ≥3 months. Patients were randomized to receive once-daily solifenacin succinate and mirabegron (5 mg/50 mg; combination), solifenacin succinate, or mirabegron (4:1:1). Safety evaluations: treatment-emergent adverse events (TEAEs), vital signs, and electrocardiogram, post-void residual volume, and laboratory assessments. Primary efficacy variables: change from baseline to end of treatment in number of incontinence episodes/24 h and micturitions/24 h.. Of 1794 patients (full analysis set), 614 (34.2%) and 168 (9.4%) were ≥65 and ≥75 years old, respectively. Overall, 856 (47.2%) patients experienced ≥1 TEAE. Higher TEAE incidences were typically observed for the combination versus both monotherapies (eg, constipation) and in the older versus younger age groups (eg, urinary tract infection). Increases in mean pulse rate from baseline of >1 bpm were noted in the combination and mirabegron younger age groups only. No clinically significant findings were observed in the other safety parameters. The efficacy variables improved with all treatments and the greatest improvements were typically observed with combination therapy.. Mirabegron and solifenacin combination therapy was a well-tolerated and effective treatment for patients with OAB symptoms irrespective of their age.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents; Young Adult

To compare the efficacy of fesoterodine or mirabegron add-on therapy for persistent overactive bladder (OAB) symptoms despite silodosin monotherapy in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, in both subjective and objective aspects.. A total of 120 patients with persistent OAB symptoms despite silodosin monotherapy were randomized to receive add-on therapy with fesoterodine (4 mg/day) or mirabegron (50 mg/day) for 12 weeks. At week 12, changes from baseline in patients' subjective symptoms and voiding/storage functions, as assessed using the International Prostate Symptom Score (IPSS), OAB symptom score (OABSS), and urodynamic studies, were compared between the groups.. The final analysis included 50 and 52 patients in the fesoterodine and mirabegron groups, respectively. Although the IPSS and OABSS significantly improved in both groups, the fesoterodine (vs mirabegron) group showed significantly greater improvements in the OABSS-total (-2.8 vs -1.5, P = 0.004), IPSS-QOL (-1.5 vs -1.1, P = 0.04), and OABSS-urgency score (-1.5 vs -0.9, P = 0.008) at 12 weeks. Regarding storage functions, although both groups showed significant improvements, the fesoterodine group demonstrated greater improvements in the detrusor overactivity alleviation rate (52.6% vs 28.9%, P = 0.03). Voiding functions did not deteriorate in either group at 12 weeks; no significant inter-group differences were observed. Post-void residual urine significantly increased by 16 mL only in the fesoterodine group.. Add-on therapy of fesoterodine to silodosin was more effective than adding mirabegron to silodosin for improving OAB symptoms and storage functions, without deteriorating voiding symptoms or functions.

Topics: Acetanilides; Aged; Aged, 80 and over; Benzhydryl Compounds; Drug Therapy, Combination; Humans; Indoles; Male; Middle Aged; Prospective Studies; Prostatic Hyperplasia; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Urological Agents

The impact of mirabegron on clinical outcome and urodynamic parameters may be important for clinical practice. Thus, the aim of this study was to compare the clinical outcomes and urodynamic effects of mirabegron (Betmiga 50 mg) versus tolterodine (Detrusitol ER 4 mg) treatment for women with overactive bladder syndrome (OAB).. Women with OAB were randomized to receive 12 weeks of mirabegron 50 mg, tolterodine extended-release 4 mg or placebo treatment. The clinical outcomes and urodynamic effects were compared between the subgroups.. Thirty-three women completed 12 weeks of mirabegron (n = 12), tolterodine (n = 12) or placebo (n = 9) treatment. A significant increase in the volumes at strong desire to void and a decrease in the daytime frequency episodes were identified in the mirabegron and tolterodine groups (all P < 0.05). Nonetheless, a decrease in the total voided volume was identified following mirabegron treatment but not tolterodine (P = 0.02).. Mirabegron and tolterodine exhibit similar changes in the urodynamics and bladder diary parameters. However, mirabegron may decrease the total voided volume. These findings may serve as an initial guide or assist in consultations regarding the treatment of OAB patients with mirabegron.

Topics: Acetanilides; Adult; Female; Humans; Middle Aged; Prospective Studies; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive; Urination; Urine; Urodynamics; Urological Agents

The objective of this study was to assess the tolerability and treatment preference in patients with overactive bladder (OAB) treated with mirabegron or tolterodine.. This was a two-period, 8-week crossover, double-blind, phase IV study (PREFER; NCT02138747) in treatment-naive adults with OAB for 3 months or longer randomized to one of four treatment sequences in a 5:5:1:1 ratio (mirabegron/tolterodine, tolterodine/mirabegron, mirabegron/mirabegron, or tolterodine/tolterodine), separated by a washout period of 2 weeks. The primary endpoint was drug tolerability using the Medication Tolerability scale of the OAB Treatment Satisfaction (OAB-S) questionnaire at end of treatment (EoT). Period-by-treatment interactions were analyzed to determine any effect of drug order. Patient preference, change from baseline in OAB symptoms, and treatment-emergent adverse events (TEAEs) were assessed.. A total of 358 randomized patients completed the OAB-S Medication Tolerability scale questionnaire at one or more visits after the baseline evaluation. The mean (95% CI) OAB-S Medication Tolerability scores were significantly higher (better tolerability) for mirabegron (86.29 [83.50, 89.08]) than for tolterodine (83.40 [80.59, 86.20]; p = 0.004). The period-by-treatment interaction was not significant (p = 0.955). Improvements in OAB-S Medication Tolerability scores at EoT were more evident in women, patients aged ≥65 years, and in patients without baseline incontinence, and were greater with mirabegron than with tolterodine extended release. There were no significant differences in patient preference or improvements in OAB symptoms. Significant differences in favor of mirabegron were observed for anticholinergic TEAEs (20.4% vs. 27.4%; p = 0.042) and specifically for gastrointestinal disorders (14.7% vs. 22.5%; p = 0.015).. Tolerability of mirabegron was significantly higher than that of tolterodine, and patient preference and improvements in OAB symptoms were comparable. Both treatments were well tolerated; however, anticholinergic side effects were higher with tolterodine.

Topics: Acetanilides; Adult; Aged; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Preference; Prospective Studies; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To evaluate patient-reported outcomes (PROs) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial.. Following a 4-week placebo run-in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg, (combination 5 + 50 mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg or placebo for 12 weeks, followed by a 2-week washout period. At each visit, PROs related to quality of life, symptom bother, and treatment satisfaction were assessed, including OAB-q Symptom Bother score, health-related quality of life (HRQOL) Total score, treatment satisfaction-visual analogue scale (TS-VAS), and patient perception of bladder condition (PPBC) questionnaires.. Overall, 3527 patients were randomized into the study, with 3494 receiving double-blind treatment. At end of treatment (EoT), both combination groups showed greater improvements in OAB-q Symptom Bother score compared with the monotherapy groups (nominal P < 0.001). Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus monotherapy groups (P ≤ 0.002). For both combination groups, the OAB-q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy (P < 0.05). The mean adjusted changes from baseline to EoT for PPBC were greater in the combination groups compared with monotherapy groups.. PROs showed that combination therapy provided clear improvements and an additive effect for many HRQOL parameters, including OAB-q Symptom Bother score, HRQOL Total score, and PPBC.

Topics: Acetanilides; Double-Blind Method; Drug Therapy, Combination; Humans; Patient Reported Outcome Measures; Quality of Life; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents; Visual Analog Scale

To evaluate the feasibility of discontinuing treatment with mirabegron once symptoms have subsided in patients with overactive bladder (OAB).. The present study evaluated a total of 159 female OAB patients (age 62.9 ± 12.36), each of which were prescribed 50 mg/day mirabegron (Time point 1-T1). Data obtained from voiding diaries and patient-reported outcome variables were assessed during follow-up visits at months 1, 3, 6, 12, 18 (T2), and 21 (T4). At the 18-month visit, patients with an Urgency Bother-Visual Analog Scale score of ≤ 50% were advised to stop treatment with mirabegron. Upon re-emergence or worsening of OAB symptoms, patients were allowed to start taking medication again at their discretion (T3). Statistical analysis was performed using a Chi-square test. An ANOVA analysis and a two-sample t test were used to evaluate differences between groups.. A total of 56 out of 159 (35.3%) patients took 50 mg of mirabegron daily between T1 and T2. A total of 17 out of 56 patients (30.4%) did not meet the criteria for mirabegron discontinuation (Group A). A total of 24 out of 56 patients (42.9%) stopped taking the medication temporarily, but later returned to treatment (Group B). The average time span between T2 and T3 was 53.9 days. Fifteen of 56 patients (26.8%) ceased treatment with mirabegron without starting it again before T4 (Group C). The average time span between T2 and T4, in Group C, was 124.7 days.. A small percentage of OAB patients were able to discontinue mirabegron due to symptom cessation.

Topics: Acetanilides; Aged; Feasibility Studies; Female; Humans; Middle Aged; Patient Reported Outcome Measures; Prospective Studies; Recurrence; Severity of Illness Index; Symptom Assessment; Thiazoles; Time Factors; Urinary Bladder, Overactive; Urological Agents; Withholding Treatment

To assess the efficacy and safety of mirabegron in the treatment of neurogenic detrusor overactivity.. This prospective, multicenter, randomized, double-blind, placebo-controlled study was conducted in three tertiary centers, and included 78 patients suffering from spinal cord injury or multiple sclerosis. Patients were randomized for Mirabegron 50 mg (Group A) or placebo (Group B). Urodynamic parameters, the 24 h pad-weight test, and patient-reported outcomes were assessed. Safety assessments included monitoring the incidence and severity of adverse events. Changes in time and differences between groups were assessed with nonparametric Kruskal-Wallis one-way analysis of variance; P ≤ 0.05 was considered statistically significant.. In total, 66 patients were eligible for inclusion in the final analysis. There was a significant increase of volume at the first detrusor contraction (P = 0.00047) and an improvement in bladder compliance (P = 0.0041) in the mirabegron group compared with the placebo-treated group, whereas the increase in cystometric capacity did not reach statistical significance (P = 0.061). There was a clear tendency to reduced urine leakage (P = 0.056) in Group A. There were significant changes in all the patient-reported outcomes, favoring the mirabegron group. The incidence of drug-related adverse events was 3.13%.. Mirabegron (50 mg) improved both urodynamic variables and patient-reported outcomes in patients with NDO. The treatment was tolerated well.

Topics: Acetanilides; Adolescent; Adult; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Reported Outcome Measures; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Urological Agents; Young Adult

The PREFER study was an assessment of medication tolerability, treatment preference and symptom improvement during treatment with mirabegron (M) and tolterodine (T) extended release (ER) in patients with overactive bladder (OAB). In this analysis of PREFER, patient-reported outcomes (PROs) were assessed during treatment.. PREFER was a two-period, 8-week crossover, double-blind, phase IV study (NCT02138747) of treatment-naïve adults with OAB ≥3 months randomized to 1 of 4 treatment sequences (M/T; T/M; M/M; T/T), separated by a 2-week washout. Tolterodine ER was dosed at 4 mg for 8 weeks and mirabegron was dosed at 25 mg for 4 weeks then increased to 50 mg for the next 4 weeks. At each visit, PROs related to treatment satisfaction, quality of life and symptom bother were assessed using the OAB Satisfaction (OAB-S; 3 independent scales/5 single-item overall assessments), OAB-q (total health-related QoL [HRQoL] and subscales [Sleep, Social, Coping, Concern] and Symptom Bother scale) and Patient Perception of Bladder Condition (PPBC) questionnaires. Responder rates were reported for OAB-q subscales based on a minimal important difference (MID; ≥ 10-point improvement) and OAB-S Medication Tolerability score ≥ 90.. In total, 358 randomized patients received ≥1 dose of double-blind study medication and completed ≥1 post-baseline value (OAB-S scale, OAB-q, PPBC): M/T (n = 154), T/M (n = 144), M/M (n = 30) or T/T (n = 30). At end of treatment (EoT), mirabegron and tolterodine ER were associated with similar mean improvements in 7 of the 8 OAB-S scores investigated, OAB-q scales and PPBC. A higher percentage of patients achieved clinically relevant improvements (MID) in OAB-q scales and OAB-S Medication Tolerability score during treatment with mirabegron than tolterodine ER.. On average, patients with OAB experienced improvements in treatment satisfaction, HRQoL and symptom bother that were of a similar magnitude during treatment with mirabegron or tolterodine ER. However, during mirabegron treatment, patients were more likely to achieve clinically relevant improvements in tolerability and HRQoL (as measured by the MID for the OAB-q or an OAB-S Medication Tolerability score ≥ 90) than during tolterodine ER treatment.. NCT02138747 ; registered May 13, 2014.

Topics: Acetanilides; Adult; Aged; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Reported Outcome Measures; Patient Satisfaction; Prospective Studies; Quality of Life; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive; Urological Agents

The long-term potential of solifenacin and mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed.. To evaluate the safety and efficacy of solifenacin succinate 5mg plus mirabegron 50mg tablets (combination treatment) versus solifenacin or mirabegron monotherapy in patients with OAB over 12 mo.. Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients.. The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h.. The median age was 60 yr (range 19-86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; mirabegron 126 patients, 41%; solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; solifenacin 18 patients, 5.9%; mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to mirabegron and solifenacin for the number of incontinence episodes (vs mirabegron: adjusted mean difference [AMD] -0.5, 95% confidence interval [CI] -0.7 to -0.2, p<0.001; vs solifenacin: AMD -0.1, 95% CI -0.4 to 0.1, p=0.002) and micturitions (vs mirabegron: AMD -0.5, 95% CI -0.8 to -0.2, p<0.001; vs solifenacin: AMD -0.4, 95% CI -0.7 to -0.1, p=0.004).. Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic.. This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.

Topics: Acetanilides; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Solifenacin Succinate; Symptom Assessment; Thiazoles; Time; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

Αim of the study was to determine the effect of mirabegron, used for overactive bladder (OAB) treatment, on female sexual function.. Eighty five sexually active women suffering from overactive bladder were prospectively enrolled in this study. Females were divided into two groups. In Group A (control), 48 patients received no treatment and in Group B, 37 patients received mirabegron 50 mg/daily for 3 months. Patients were evaluated with FSFI-Gr at the beginning of the study and again after a period of 3 months.. In Group B, there was a significant increase post-treatment compared to baseline (p < 0.001) in total FSFI (20.3 (3.8) to 26.6 (4.2)) and all domains (desire: 3.0 (1.2) to 4.8 (1.2)), arousal: 3.0 (0.8) to 4.8 (0.9), lubrication: 3.9 (1.1) to 4.8 (1.2), orgasm: 3.6 (0.8) to 4.8 (1.0), satisfaction: 3.2 (0.4) to 4.0 (0.8) and pain: 3.2 (0.8) to 4.4 (1.2)). In Group A, there were no statistically significant changes in pre- and post-observation values.. This study is one of the few demonstrating that management of OAB with mirabegron improves female sexual function.. TRN ISRCTN17199301 , 20/10/2017, retrospectively registered.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Female; Humans; Middle Aged; Orgasm; Prospective Studies; Sexual Health; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To determine the effectiveness of mirabegron in patients with neurogenic lower urinary tract dysfunction.. Randomized, double-blind, placebo-controlled study. Canadian patients with spinal cord injury (SCI) or multiple sclerosis (MS) with urinary symptoms and incontinence were recruited. Patients were randomized to mirabegron 25 mg (or an identical placebo) for 2 weeks at which point a dose escalation to mirabegron 50 mg (or an identical placebo) was maintained for 8 weeks. Urodynamics were performed before and after treatment. The primary outcome measure was maximum cystometric capacity (MCC). Intention to treat analysis and ANCOVA models (with adjustment for baseline values) were used and marginal means (MM) are reported; P-value <0.05 was considered significant.. Among patients with SCI or MS, we demonstrated non-significant trends towards improvement in some urodynamic parameters with mirabegron 50 mg compared to placebo, and a significantly lower neurogenic bladder symptom burden.

Topics: Acetanilides; Adult; Aged; Canada; Double-Blind Method; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Pilot Projects; Spinal Cord Injuries; Thiazoles; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics

To compare persistence with medication and the reasons for discontinuation of mirabegron or solifenacin therapy up to12 months in women with overactive bladder (OAB).. Female OAB patients who presented to women's urology clinics were enrolled in a prospective, randomized, two-arm study. Patients were randomized to receive mirabegron at 25-50 mg (n = 76) or solifenacin at 2.5-5 mg (n = 72). The persistence rate and the reasons for discontinuation were investigated up to 12 months.. The 12-month persistence rate was 12.2% in the mirabegron group versus 20.1% in the solifenacin group and there were no significant differences of the persistence rates during the study (n.s). Patients discontinued treatment because of lack of efficacy (21.6%), spontaneous improvement (18.2%), and side-effects (17.6%), while 19.6% were lost to follow up. Discontinuation due to side-effects was significantly more frequent in the solifenacin group than the mirabegron group (27.3 vs. 7.9%, P < 0.05). In contrast, discontinuation due to lack of efficacy was significantly more frequent in the mirabegron group than the solifenacin group (36.8 vs. 5.6%, P < 0.05).. This study demonstrated low persistence rates over 12 months for both mirabegron and solifenacin, although the reasons for discontinuation were somewhat different.

Topics: Acetanilides; Drug Substitution; Female; Humans; Long-Term Care; Postmenopause; Prospective Studies; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To evaluate the potential of solifenacin 5 mg combined with mirabegron 25 or 50 mg to deliver superior efficacy compared with monotherapy, with acceptable tolerability, in the general overactive bladder (OAB) population with urinary incontinence (UI).. After a 4-week placebo run-in, patients aged ≥18 years with wet OAB (urgency, urinary frequency and UI) for ≥3 months who recorded on average ≥8 micturitions/24 h, ≥1 urgency episode/24 h, and ≥3 UI episodes over the 7-day micturition diary, were eligible for randomisation to double-blind treatment [2:2:1:1:1:1 ratio, solifenacin 5 mg + mirabegron 25 mg (combined S5 + M25 group); solifenacin 5 mg + mirabegron 50 mg (combined S5 + M50 group); solifenacin 5 mg; mirabegron 25 mg; mirabegron 50 mg; or placebo for 12 weeks], and 2-weeks' single-blind, placebo run-out. Co-primary efficacy variables were change from baseline to end of treatment (EoT) in the mean number of UI episodes/24 h and micturitions/24 h, assessed using a 7-day electronic micturition diary. Secondary efficacy variables included change from baseline to EoT in the mean volume voided/micturition, change from baseline at weeks 4, 8, 12 and EoT in mean number of UI episodes/24 h, micturitions/24 h, urgency episodes/24 h, urgency UI (UUI) episodes/24 h and nocturia episodes/24 h; the percentage of patients (responders) achieving zero UI episodes/24 h at EoT in the last 7 days prior to each visit, micturition frequency normalisation (<8 episodes/24 h) at weeks 4, 8, 12 and EoT; and the number of UUI episodes and nocturia episodes in the 7-day diary. Safety assessments included incidence and frequency of treatment-emergent adverse events (TEAEs), post-void residual (PVR) urine volume, and changes from baseline in laboratory parameters.. Whilst the combined S5 + M50 group was superior to solifenacin 5 mg for UI, with a mean (standard error) adjusted difference of -0.20 (0.12) UI episodes/24 h (95% confidence interval -0.44, 0.04, P = 0.033), there was no statistical superiority vs mirabegron 50 mg [-0.23 (0.12) UI episodes/24 h; P = 0.052]. In secondary analyses, all active treatment groups had greater improvements in UI episodes/24 h vs placebo, with effect sizes for the combined therapy groups (combined S5 + M25 group: -0.70 episodes/24 h; combined S5 + M50 group: -0.65 episodes/24 h) that were substantially higher than those obtained with monotherapy (range -0.37 episodes/24 h for mirabegron 25 mg to -0.45 episodes/24 h for solifenacin 5 mg). For micturitions/24 h, adjusted change from baseline to EoT was greater in the combined therapy groups vs monotherapies (combined S5 + M50 group, nominal P values 0.006 and <0.001 vs solifenacin 5 mg and mirabegron 50 mg, respectively; combined S5 + M25 group, nominal P values 0.040 and 0.001 vs solifenacin 5 mg and mirabegron 25 mg, respectively). All active treatment groups had greater improvements in the mean numbers of micturitions/24 h vs placebo, with effect sizes for the combined therapy groups (combined S5 + M25 group: -0.85 micturitions/24 h; combined S5 + M50 group: -0.95 micturitions/24 h) higher than with mirabegron monotherapy (25 mg: -0.36; 50 mg: -0.39 micturitions/24 h) and solifenacin 5 mg (-0.56 micturitions/24 h). The combined S5 + M50 group was statistically significantly superior to both monotherapies at EoT for UUI episodes, urgency episodes and nocturia, with effect sizes that appeared to be additive. The combined S5 + M25 group was statistically significantly superior to mirabegron 25 mg for the same variables, except for nocturia. In responder analyses at the EoT, odds ratios in favour of both combined therapies vs monotherapies were shown for the proportion of patients with zero UI episodes and those achieving micturition frequency normalisation. There was a slightly increased frequency of TEAEs in the combined therapy groups vs monotherapies and placebo. Most of the TEAEs were mild or moderate in severity. Events indicative of urinary retention were reported slightly more frequently in the combined therapy groups vs monotherapy and placebo. PVR volume was slightly increased in the combined therapy groups vs solifenacin 5 mg, mirabegron monotherapy, and placebo groups. There were slightly higher frequencies of dry mouth,. In the largest OAB study to date, combined therapy with solifenacin 5 mg + mirabegron 25 mg and solifenacin 5 mg + mirabegron 50 mg provided consistent improvements in efficacy compared with the respective monotherapies across most of the outcome parameters, with effect sizes generally consistent with an additive effect. Although the combined S5 + M50 group did not achieve a statistically significant effect vs mirabegron 50 mg in the primary analysis of one of the co-primary endpoints (change from baseline in mean number of UI episodes/24 h), it approached statistical significance (P = 0.052), and the nominal P values for the other co-primary endpoint (micturitions/24 h) were <0.05. Most effects of combined therapy vs monotherapy were observable by week 4. The clinical relevance of the improvements seen with combined therapy for several objective OAB outcome measures was also supported by the improvements of combined therapy vs monotherapy in the responder analyses.

Topics: Acetanilides; Adult; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Internationality; Male; Maximum Tolerated Dose; Middle Aged; Multivariate Analysis; Risk Assessment; Single-Blind Method; Solifenacin Succinate; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

In the BESIDE study, combination therapy (antimuscarinic [solifenacin] and β. OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-week single-blind run-in, were randomised 1:1:1 to double-blind daily combination (solifenacin 5 mg/mirabegron 25 mg, increasing to 50 mg after week 4), solifenacin 5 or 10 mg for 12 weeks. CV safety assessments included frequency of CV-related treatment-emergent adverse events (TEAEs), change from baseline in vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse rate) and electrocardiogram (ECG) parameters.. The frequency of hypertension, tachycardia and ECG QT prolongation, respectively, was low and comparable across combination (1.1%, 0.3%, 0.1%), solifenacin 5 mg (0.7%, 0.1%, 0.1%), and solifenacin 10 mg groups (0.8%, 0%, 0.1%). Adjusted mean (SE) change from baseline to end of treatment (EoT) in SBP, DBP, and pulse rate with combination (0.07 mm Hg [0.38], -0.35 mm Hg [0.26], 0.47 bpm [0.28]), solifenacin 5 mg (-0.93 mm Hg [0.38], -0.45 mm Hg [0.26], 0.43 bpm [0.28]) and solifenacin 10 mg (-1.28 mm Hg [0.38], -0.48 mm Hg [0.26], 0.27 bpm [0.28]) was generally comparable, with the exception of a mean treatment difference of ~1 mm Hg in SBP between combination and solifenacin monotherapy; SBP was unchanged with combination and decreased with solifenacin monotherapy. Mean changes from baseline to EoT in ECG parameters were generally similar across treatment groups, except for QT interval corrected using Fridericia's formula, which was higher with solifenacin 10 mg (3.30 mseconds) vs. combination (0.49 mseconds) and solifenacin 5 mg (0.77 mseconds).. The comparable frequency of CV-related TEAEs, changes in vital signs and ECG parameters indicates no synergistic effect on CV safety outcomes when mirabegron and solifenacin are combined.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscarinic Antagonists; Single-Blind Method; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

The aim of this study was to compare outcomes using two preference-based measures of health status (EQ-5D-5L and OAB-5D) in patients with overactive bladder (OAB) treated with solifenacin plus mirabegron or solifenacin monotherapy in the BESIDE trial.. Patients with OAB who remained incontinent after 4 weeks' treatment with solifenacin 5 mg were randomized 1:1:1 to combination treatment (solifenacin 5 mg plus mirabegron [25 mg for the first 4 weeks/50 mg for the last 8 weeks]), solifenacin 5 mg, or solifenacin 10 mg. EQ-5D-5L and OAB-q were administered at baseline, weeks 4, 8, 12, and end of treatment (EoT). OAB-5D scores were derived from OAB-q results. Responder analysis was carried out using several definitions of minimally important difference.. A total of 2054 patients received one or more doses of study treatment (combination, n = 694; solifenacin 5 mg, n = 684; solifenacin 10 mg, n = 676). EQ-5D-5L Index mean score changes (from baseline to EoT) were greater with combination (0.059) than with solifenacin 5 mg (0.040) and 10 mg (0.044) monotherapy, but the differences were not statistically significant. A significantly greater improvement was observed for combination on OAB-5D (0.107 vs 0.085 for 5 mg, and 0.087 for 10 mg; p ≤ 0.01). The dimensions most improved overall were anxiety/depression, pain/discomfort, and usual activities on EQ-5D-5L, and urge, urine loss, and coping on OAB-5D. The proportion of responders was significantly greater with combination compared with monotherapy using OAB-5D only.. Improvements were observed in all study arms on both the EQ-5D-5L and OAB-5D, although only the OAB-5D showed a statistically significant benefit for combination versus solifenacin monotherapy. Combining generic and condition-specific preference-based health status measures allowed for assessment of dimensions that were particularly relevant to this patient population, while permitting comparison with outcomes from other studies, treatments, and populations via EQ-5D.

Topics: Acetanilides; Adult; Aged; Double-Blind Method; Drug Therapy, Combination; Female; Health Status; Humans; Male; Mental Health; Middle Aged; Patient Reported Outcome Measures; Quality of Life; Solifenacin Succinate; Surveys and Questionnaires; Thiazoles; Urinary Bladder, Overactive; Urological Agents

The BESIDE study demonstrated that combination therapy (mirabegron and solifenacin 5mg) improved overactive bladder symptoms versus solifenacin 5mg or 10mg, and was well tolerated.. To ensure efficacy and safety is maintained in older patients (>65 yr), who usually experience greater symptom severity and comorbidities, a prespecified subanalysis stratified by age group was conducted.. Patients remaining incontinent (≥1 episode during 3-d diary) following 4-wk single-blind daily solifenacin 5mg were randomized 1:1:1 to a daily double-blind combination (solifenacin 5mg and mirabegron 25mg, increased to 50mg at wk 4), solifenacin 5mg or 10mg for 12 wk. Four cohorts stratified by age (<65 yr, ≥65 yr and < 75 yr, ≥75 yr) were investigated.. Efficacy assessments: change from baseline to end of treatment in average daily incontinence (primary) and micturition frequency (key secondary), number of incontinence episodes during the 3-d diary (key secondary), and change from baseline in average daily urgency and urgency incontinence episodes. Safety included treatment-emergent adverse events and vital signs.. Full analysis set included 2110 patients: 30.9% aged ≥65 yr and 8.9% aged ≥75 yr. At the end of treatment, daily, and 3-d incontinence daily micturitions, urgency, and urgency incontinence, were improved in each treatment group and age group; the largest reductions were observed with combination in each age cohort. There were no notable differences in vital signs or the incidence of treatment-emergent adverse events between treatment and age groups, with the exception of dry mouth, which was highest with solifenacin 10mg.. Efficacy and safety in the overall population is maintained in older (≥65 yr) and elderly (≥75 yr) patients treated with a combination of solifenacin and mirabegron, or solifenacin monotherapy; irrespective of age, combination was associated with the greatest improvement in overactive bladder symptoms.. This study investigated the effectiveness and safety of a combination of two different treatments (mirabegron 50mg and solifenacin 5mg) or solifenacin (5mg or 10mg) alone in patients aged <65 yr or ≥65 yr, and <75 yr or ≥75 yr with overactive bladder. Symptoms of overactive bladder, such as the urgent need to visit the toilet, incontinence, and frequent urination, were improved with all treatments regardless of the patient's age, but combination treatment demonstrated the greatest benefit, and was well tolerated.

Topics: Acetanilides; Aged; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Muscarinic Antagonists; Single-Blind Method; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

We aimed to compare the efficacy and safety of mirabegron, a β3-adrenoceptor agonist, and imidafenacin, an anticholinergic agent, in overactive bladder patients.. We conducted a multicenter, prospective randomized cross-over study at 5 hospitals in Japan from December 2012 to June 2015. We enrolled female patients with overactive bladder aged ≥50 years, who had never received treatment for the condition. The patients were assigned to Group A or B. Group A patients were administered mirabegron (50 mg per day) for 8 weeks, followed by a 2-week washout period, and then imidafenacin (0.2 mg per day) for 8 weeks. This order of drug administration was reversed in Group B.. A total of 33 and 18 patients in Group A and 37 and 26 patients in Group B continued to receive treatment at weeks 8 and 18, respectively. Mirabegron administration significantly improved overactive bladder symptom score (OABSS), the urinary frequency per 24 hr, voided volume per micturition, and number of nocturia episodes per night at week 8. Moreover, imidafenacin administration improved all these variables, except for the number of nocturia episodes per night at week 8. No significant difference was observed in the drug effects between mirabegron and imidafenacin. Although imidafenacin administration significantly increased the scores for dry mouth, blurred vision, and constipation, mirabegron administration did not.. Mirabegron and imidafenacin have the same efficacy. Imidafenacin administration is associated with a higher rate of dry mouth, blurred vision, and constipation as compared to mirabegron administration. Neurourol. Urodynam. 36:1097-1103, 2017. © 2016 Wiley Periodicals, Inc.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Aged, 80 and over; Cross-Over Studies; Female; Humans; Imidazoles; Middle Aged; Muscarinic Antagonists; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

This large dose-ranging study explored the benefits of different combinations of mirabegron and solifenacin on health-related quality of life (HRQoL), based on patient-reported outcomes (PROs), and patients ('responders') achieving clinically meaningful improvements in efficacy and HRQoL.. SYMPHONY (NCT01340027) was a Phase II, placebo- and monotherapy-controlled, dose-ranging, 12-week trial. Adult patients with overactive bladder (OAB) for ≥3 months were randomized to 1 of 12 groups: 6 combination (solifenacin 2.5/5/10 mg + mirabegron 25/50 mg), 5 monotherapy (solifenacin 2.5/5/10 mg, or mirabegron 25/50 mg), or placebo. Change from baseline to end of treatment was assessed, versus placebo and solifenacin 5 mg in: PROs (OAB-q [Symptom Bother/total HRQoL] and Patient Perception of Bladder Condition score), and responders achieving minimally important differences (MIDs) in PROs and predetermined clinically meaningful improvements in efficacy (e.g. <8 micturitions/24 h). Changes in PROs and responders were analysed using an ANCOVA model and logistic regression, respectively.. The Full Analysis Set included 1278 patients. Combination therapy of solifenacin 5/10 mg + mirabegron 25/50 mg significantly improved PROs versus solifenacin 5 mg and placebo, and significantly more responders achieved MIDs in PROs and efficacy. Micturition frequency normalization was approximately twofold greater with 10 + 25 mg (OR 2.06 [95 % CI 1.11, 3.84; p = 0.023]) and 5 + 50 mg (OR 1.91 [95 % CI 1.14, 3.21; p = 0.015]) versus solifenacin 5 mg.. Combining mirabegron 25/50 mg and solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg.

Topics: Acetanilides; Adult; Aged; Double-Blind Method; Drug Therapy, Combination; Female; Health Status; Humans; Male; Middle Aged; Minimal Clinically Important Difference; Patient Reported Outcome Measures; Quality of Life; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To investigate safety, tolerability and efficacy of long-term (52 weeks) open-label treatment with mirabegron 50 mg, with an optional dose increase to 100 mg, in patients with overactive bladder (OAB).. Patients received mirabegron 50 mg once daily for 52 weeks. If efficacy was insufficient at week 8, the dose could be increased to 100 mg. Safety was evaluated based on vital signs, adverse events (AEs), laboratory findings, electrocardiogram and post-void residual volume. Treatment efficacy was assessed with a 3-day micturition diary and the King's Health Questionnaire (KHQ).. Two hundred and four patients were enrolled; mirabegron dose was maintained at 50 mg in 153 patients and increased to 100 mg in 50 patients. Mirabegron was well tolerated at both doses. Incidences of AEs and treatment-related AEs were 91.4% and 33.6% in patients on 50 mg, and 100% and 30.0% in patients on 100 mg, respectively. Time course changes in systolic or diastolic blood pressure and pulse rate were not considered clinically significant. At the end of treatment (EOT), patients on 50 mg and 100 mg showed improvement in frequency and urgency. Improvements from baseline to EOT in quality of life scores were observed for all KHQ domains.. There were no safety or tolerability concerns associated with mirabegron 50 mg (with an optional dose increase to 100 mg) over 52 weeks. Improvement in micturition variables was maintained with mirabegron 50 mg from weeks 8 to 52.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Young Adult

To provide a clinical view and interpretation on the methods for analysis of incontinence in patients with overactive bladder.. Results are analyzed using the total number of incontinence episodes in a 3-day diary period, using fixed and random effect Poisson regression models to calculate ratio of event rates and 95% confidence interval (CI) together with P-values and are compared with the analysis of the mean number of incontinence episodes/24 hr using analysis of covariance models to calculate P-values and 95% CI for the difference between treatments.. Using random effects Poisson regression models demonstrated that the number of incontinence episodes was reduced by 26% more with mirabegron 50 mg than with placebo. For solifenacin 5 and 10 mg, treatment resulted in a 43% (41%) greater decrease in the number of incontinence episodes compared with placebo.. Instead of providing a fixed number of incontinence episodes/24 hr that reflects the mean effect, the estimate using Poisson methodology provides an efficacy estimate that can be interpreted in the context of, and relative to, the patient's baseline (severity). Using the total number of incontinence episodes in the diary period, and expressing this as percent decrease in the number of episodes, may be easier to interpret; for example, because this results in a relative measure of effect that provides an alternative understanding of a patient's improvement at end of treatment compared with the comparator arm. Also, it is based on statistical methods that are more suitable for the analysis of count data. Neurourol. Urodynam. 35:728-732, 2016. © 2015 Wiley Periodicals, Inc.

Topics: Acetanilides; Humans; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

To assess patient-reported outcomes (PROs) in patients with overactive bladder (OAB) receiving the novel β. Data from a randomised, double-blind, controlled phase III trial in 1,987 patients aged ≥18 years with OAB symptoms for ≥3 months were analysed. Patients received placebo, mirabegron 50 or 100 mg/day, or tolterodine extended release (ER) 4 mg orally once daily for 12 weeks after a 2-week placebo run-in. Prespecified analysis of PROs (changes in OAB Questionnaire [OAB-q], Patient Perception of Bladder Condition [PPBC], and Work Productivity and Activity Impairment: Specific Health Problem [WPAI-SHP] instrument) in patients treated with mirabegron 50 mg/day, tolterodine ER 4 mg/day or placebo is reported. Post-hoc analyses of OAB-q, PPBC and the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) in patients who were incontinent at baseline are also reported.. Significant improvements over placebo in OAB-q coping and concern from baseline to final visit were observed with mirabegron 50 mg/day. No significant improvements in these parameters were observed with tolterodine ER 4 mg/day. Mirabegron 50 mg/day significantly increased the proportion of patients showing a PPBC improvement over placebo. Mirabegron 50 mg/day also produced greater improvements in WPAI-SHP presenteeism and greater reductions in absenteeism and overall work impairment than placebo or tolterodine ER 4 mg/day. The impact of mirabegron 50 mg/day treatment on PROs in the incontinent population appears to be greater than that in the overall OAB population.. At the approved dose of 50 mg/day, mirabegron significantly improves OAB patients' perception of disease and quality of life, independent of whether they are incontinent at baseline. Neurourol. Urodynam. 35:987-994, 2016. © 2015 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.

Topics: Absenteeism; Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Double-Blind Method; Female; Humans; Incontinence Pads; Male; Middle Aged; Muscarinic Antagonists; Patient Reported Outcome Measures; Quality of Life; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

A multicriteria decision analysis (MCDA) approach was developed and used to estimate the benefit-risk of solifenacin and mirabegron and their combination in the treatment of overactive bladder (OAB). The objectives were 1) to develop an MCDA tool to compare drug effects in OAB quantitatively, 2) to establish transparency in the evaluation of the benefit-risk profile of various dose combinations, and 3) to quantify the added value of combination use compared to monotherapies. The MCDA model was developed using efficacy, safety, and tolerability attributes and the results of a phase II factorial design combination study were evaluated. Combinations of solifenacin 5 mg and mirabegron 25 mg and mirabegron 50 (5+25 and 5+50) scored the highest clinical utility and supported combination therapy development of solifenacin and mirabegron for phase III clinical development at these dose regimens. This case study underlines the benefit of using a quantitative approach in clinical drug development programs.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Decision Support Techniques; Drug Dosage Calculations; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Male; Muscarinic Antagonists; Risk Assessment; Risk Factors; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

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.. To evaluate the efficacy and the safety and tolerability of combination (solifenacin 5mg and mirabegron 50mg) versus solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of solifenacin 5mg.. OAB patients remaining incontinent despite daily solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25mg increasing to 50mg after week 4.. 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 5mg, noninferiority (and potential superiority) of combination versus solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus solifenacin monotherapy.. A total of 2174 patients were randomised to combination (n=727), solifenacin 5mg (n=728), or solifenacin 10mg (n=719). At EOT, combination was superior to solifenacin 5mg, 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 10mg for key secondary end points and superior to solifenacin 10mg for improving daily micturitions. All treatments were well tolerated.. Adding mirabegron 50mg to solifenacin 5mg further improved OAB symptoms versus solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5mg.. In this 12-wk study, overactive bladder patients who remained incontinent despite initial solifenacin 5mg treatment received additional treatment with mirabegron 50mg. Combining mirabegron 50mg with solifenacin 5mg was superior to solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated.. ClinicalTrials.gov NCT01908829.

Topics: Acetanilides; Adult; Aged; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Retreatment; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

We investigated improvements in overactive bladder and patient reported outcomes in patients with overactive bladder and refractory incontinence treated with mirabegron 50 mg plus solifenacin 5 mg vs solifenacin 5 or 10 mg.. Patients with overactive bladder who were incontinent despite 4 weeks of single-blind daily solifenacin 5 mg were randomized 1:1:1 to a double-blind daily combination of mirabegron 50 mg/solifenacin 5 mg, or solifenacin 5 or 10 mg for 12 weeks. The mirabegron dose was increased from 25 to 50 mg after week 4. Symptom bother, health related quality of life and patient perception of bladder condition were assessed by OAB-q (Overactive Bladder Questionnaire) and the PPBC (Patient Perception of Bladder Condition) questionnaire, respectively. Responder rates were based on a 50% reduction in daily incontinence, zero incontinence episodes and fewer than 8 micturitions per 24 hours with minimal important differences in OAB-q and PPBC.. Overall 2,174 patients with a median age of 59 years were randomized, including 727 to the combination, 728 to solifenacin 5 mg and 719 to solifenacin 10 mg. Symptom bother, total health related quality of life and its subscales (coping, concern and social), and PPBC were significantly improved with combination vs solifenacin monotherapy (p <0.05). The odds of achieving clinically meaningful improvements in incontinence, micturition frequency, symptom bother, health related quality of life and PPBC were significantly higher for combination than solifenacin monotherapy. The odds of becoming continent was 47% and 28% higher for combination vs solifenacin 5 and 10 mg (OR 1.47, 95% CI 1.17-1.84, p = 0.001 and OR 1.28; 95% CI 1.02-1.61, p = 0.033, respectively).. Significantly more patients on the combination achieved clinically meaningful improvements in incontinence and micturition frequency. Improvements were accompanied by similar improvements in PPBC, symptom bother and health related quality of life.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscarinic Antagonists; Quality of Life; Solifenacin Succinate; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics; Young Adult

We assessed clinical and urodynamic effects of solifenacin versus mirabegron in women with overactive bladder (OAB) syndrome.. Eighty women with OAB were randomized into 2 groups. In group A, the patients received solifenacin 5 mg once a day for 12 weeks; in group B, the patients received mirabegron 50 mg once a day for 12 weeks. Symptoms were assessed with OAB Symptom Score (OABSS). Patients underwent urodynamic investigation with pressure flow study. OABSS and urodynamic study were performed before and after treatment.. Both solifenacin and mirabegron were effective in improving OAB symptoms. Mirabegron showed greater tolerability with fewer patients discontinuing therapy because of side effects. Both solifenacin and mirabegron were effective in improving the storage function in the pressure flow study, but solifenacin showed a significant reduction of the detrusor pressure in the voiding phase with an increase in the postvoid residual urine volume.. Mirabegron has shown to be a drug with the better balance between efficacy and tolerability in women with OAB.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Female; Humans; Middle Aged; Muscarinic Antagonists; Prospective Studies; Single-Blind Method; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Double-Blind Method; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive

To assess the effect of 25 or 50 mg mirabegron on cardiovascular end-points and adverse drug reactions in real-world Japanese patients with overactive bladder and cardiovascular disease.. Participants had overactive bladder, a history of/coexisting cardiovascular disease and a 12-lead electrocardiogram carried out ≤7 days before initiating 4 weeks of mirabegron treatment. Patients with "serious cardiovascular disease" (class III or IV on the New York Heart Association functional classification and further confirmed by expert analysis) were excluded. Patient demographics, physical characteristics and cardiovascular history were recorded. After 4 weeks, patients underwent another electrocardiogram. Incidence of cardiovascular adverse drug reactions and change from baseline in electrocardiogram parameters (RR, PR, QRS intervals, Fridericia's corrected QT and heart rate) were assessed.. Of 316 patients registered, 236 met criteria and had baseline/post-dose electrocardiograms: 61.9% male; 60.2% aged ≥75 years; 93.6% with coexisting cardiovascular disease, notably, arrhythmia (67.8%) and angina pectoris (19.1%). Starting mirabegron daily doses were 25 mg (19.9%) or 50 mg (80.1%). The incidence of cardiovascular adverse drug reactions was 5.51%. After 4 weeks, the mean heart rate increased by 1.24 b.p.m. (statistically significant, but clinically acceptable as per previous trials). No significant changes were observed in PR, QRS or Fridericia's corrected QT. No significant correlations in the total population or age-/sex-segregated subgroups were observed between baseline Fridericia's corrected QT and change at 4 weeks. No correlation for heart rate versus change from baseline heart rate with treatment was observed.. Mirabegron was well tolerated in real-world Japanese patients with overactive bladder and coexisting cardiovascular disease. No unexpected cardiovascular safety concerns were observed.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Cardiovascular Diseases; Female; Humans; Male; Marketing; Thiazoles; Urinary Bladder, Overactive; Urological Agents

To evaluate the efficacy and safety of mirabegron compared with imidafenacin for the treatment of female patients with overactive bladder.. Patients (n = 89) were randomized to receive 0.1 mg imidafenacin twice daily (n = 47) or 50 mg mirabegron once daily (n = 42) for 12 weeks. The primary efficacy end-point was change in total Overactive Bladder Symptom Score. Secondary efficacy end-points included change in Overactive Bladder Symptom Score, 3-day micturition diary, International Prostate Symptom Score and Overactive Bladder Questionnaire. Safety assessments included adverse events, vital signs, post-void residual volume and patient-reported incidence, and severity of distinctive symptoms related to adverse events.. The mirabegron group showed a significantly reduced mean total Overactive Bladder Symptom Score from baseline, but no significant differences were noted in change of total Overactive Bladder Symptom Score compared with the imidafenacin group. Significant improvements in secondary efficacy end-points were observed regarding the mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean number of incontinence episodes/24 h, mean volume voided/micturition, total International Prostate Symptom Score and quality of life in both groups, with no significant differences between the groups. The overall incidence of adverse events and the incidence of dry mouth were significantly higher in the imidafenacin group than in the mirabegron group. Patient-reported incidence and the severity of dry mouth were significantly exacerbated in the imidafenacin group.. Treatment with 50 mg mirabegron once daily effectively relieves overactive bladder symptoms in women with fewer adverse events than treatment with antimuscarinics.

Topics: Acetanilides; Double-Blind Method; Female; Humans; Imidazoles; Muscarinic Antagonists; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

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.. The primary objective was to evaluate the efficacy of combinations of solifenacin/mirabegron compared with solifenacin 5mg monotherapy. The secondary objective was to explore the dose-response relationship and the safety/tolerability compared with placebo and monotherapy.. A phase 2, factorial design, randomised, 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.. A total of 1306 patients (66.4% female) were randomised 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.. 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 assessments included treatment-emergent adverse events (TEAEs), blood pressure, pulse rate, postvoid residual (PVR) volume, and laboratory and electrocardiography (ECG) parameters.. 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.. 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.. 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.. Clinical trials.gov: NCT01340027.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Double-Blind Method; Drug Combinations; Europe; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Solifenacin Succinate; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urination; Urodynamics; Urological Agents

The β3-adrenoceptor agonist mirabegron is approved for treatment of the symptoms of overactive bladder (OAB). Incontinence can be the most bothersome of OAB symptoms. Hence, we conducted a post hoc analysis of pooled data from three randomised, double-blind, placebo-controlled, 12-wk, phase 3 studies of mirabegron to evaluate the efficacy of mirabegron 50mg in incontinent OAB patients and in subgroups of patients stratified by severity of incontinence at baseline (an average of two or more [FAS-I ≥ 2 subgroup] or four or more [FAS-I ≥ 4 subgroup] incontinence episodes per 24h at baseline, where FAS-I is the full analysis set-incontinence population) and to determine correlations between measures of efficacy and disease severity. Mirabegron 50mg resulted in statistically significant improvements from baseline to final visit versus placebo in mean number of incontinence episodes, micturitions, and urgency episodes per 24h and mean volume voided per micturition in the pooled incontinent population and in the FAS-I ≥ 2 and FAS-I ≥ 4 subgroups. Treatment effect versus placebo for incontinence and urgency episodes increased with increasing severity of incontinence at baseline. Moderate correlations were seen between improvement in both frequency of incontinence episodes and micturitions and baseline incontinence and micturition frequency, respectively, with mirabegron 50mg and placebo.. Incontinence can be the most bothersome of OAB symptoms; mirabegron 50mg once daily is effective for treatment of OAB symptoms in incontinent patients, and its effect increases with increasing severity of incontinence.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Severity of Illness Index; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urination

To assess the efficacy and safety of mirabegron 50 mg once daily compared with placebo and the active control, tolterodine extended-release (ER) 4 mg once daily, in patients with symptoms of overactive bladder (OAB) in Taiwan, Korea, China, and India.. A 12-week multinational, randomized, double-blind, parallel-group placebo- and active-controlled trial. The primary efficacy endpoint was change from baseline to final visit in mean number of micturitions/24 hr. Secondary endpoints were: mean number of urgency episodes, incontinence episodes and urge incontinence episodes/24 hr, mean number of nocturia episodes per night, mean volume voided per micturition, and quality-of-life (QoL) scores as assessed by the King's Health Questionnaire (KHQ).. Of 1,126 patients who were randomized to receive double-blind study drug, 921 patients (300, 311, and 310 in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg groups, respectively) completed the treatment period. Demographic characteristics were similar across treatment groups. A statistically significant improvement versus placebo in mean number of micturitions/24 hr was seen with mirabegron 50 mg at all timepoints (P < 0.05) as well as final visit (-0.57 with 95% confidence intervals [CIs] of [-1.04, -0.09], P = 0.019). There was no significant difference between treatment groups in improvement from baseline to final visit in any of the secondary outcome measures except volume voided per micturition. The overall incidence of drug-related adverse events was 17.2%, 15.8%, and 21.3%, in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg groups, respectively.. Mirabegron 50 mg once daily for 12 weeks was superior to placebo in reducing the frequency of micturitions in patients with symptoms of OAB in Taiwan, Korea, China, and India.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Asia; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Quality of Life; Recovery of Function; Surveys and Questionnaires; Thiazoles; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urination; Urodynamics; Urological Agents

We evaluated the efficacy and safety of add-on treatment with a β3-adrenoceptor agonist (mirabegron) for overactive bladder symptoms remaining after α1-blocker (tamsulosin) treatment in men with benign prostatic obstruction.. Patients with benign prostatic obstruction with urinary urgency at least once per week and a total OABSS of 3 or more points after 8 or more weeks of treatment with tamsulosin were enrolled in the study. They were randomly allocated to receive 0.2 mg tamsulosin daily or 0.2 mg tamsulosin and 50 mg mirabegron daily for 8 weeks. The primary end point was change in total OABSS. Safety assessments included change in post-void residual urine volume and adverse events.. From January 2012 through September 2013 a total of 94 patients were randomized. Of these patients 76 completed the protocol treatment. In the full analysis set the change in total OABSS during the treatment period was significantly greater in the combination group than in the monotherapy group (-2.21 vs -0.87, p=0.012). The changes in scores for urinary urgency, daytime frequency, International Prostate Symptom Score storage symptom subscore and quality of life index at 8 weeks were significantly greater in the combination group. The change in post-void residual urine volume was significantly greater in the combination group. Although 6 patients experienced adverse events in the combination group, urinary retention was observed in only 1 patient.. Combined tamsulosin and mirabegron treatment is effective and safe for patients with benign prostatic obstruction who have overactive bladder symptoms after tamsulosin monotherapy.

Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Aged; Drug Therapy, Combination; Humans; Male; Prostatic Hyperplasia; Sulfonamides; Tamsulosin; Thiazoles; Urinary Bladder, Overactive

Overactive bladder (OAB) is highly prevalent and is associated with considerable morbidity and reduced health-related quality of life. β3-adrenergic receptor (β3-AR) stimulation is a novel alternative to antimuscarinic therapy for OAB.. The objective of this analysis was to assess the cost effectiveness of the β3-AR agonist mirabegron relative to tolterodine extended release (ER) in patients with OAB from a UK National Health Service (NHS) perspective.. A Markov model was developed to simulate the management, course of disease, and effect of complications in OAB patients over a period of 5 years. Transition probabilities for symptom severity levels and probabilities of adverse events were estimated from the results of the randomised, double-blind SCORPIO trial in 1,987 patients with OAB. Other model inputs were derived from the literature and on assumptions based on clinical experience.. Total 5-year costs per patient were £1,645.62 for mirabegron 50 mg/day and £1,607.75 for tolterodine ER 4 mg/day. Mirabegron was associated with a gain of 0.009 quality-adjusted life-years (QALYs) with an additional cost of £37.88. The resulting incremental cost-effectiveness ratio (ICER) was £4,386/QALY gained. In deterministic sensitivity analyses in the general OAB population and several subgroups, ICERs remained below the generally accepted willingness-to-pay (WTP) threshold of £20,000/QALY gained. The probability of mirabegron 50 mg being cost effective relative to tolterodine ER 4 mg was 89.4 % at the same WTP threshold.. Mirabegron 50 mg/day is likely to be cost effective compared with tolterodine ER 4 mg/day for adult patients with OAB from a UK NHS perspective.

Topics: Acetanilides; Adult; Benzhydryl Compounds; Cost-Benefit Analysis; Cresols; Double-Blind Method; Humans; Phenylpropanolamine; Quality of Life; Thiazoles; Tolterodine Tartrate; United Kingdom; Urinary Bladder, Overactive; Urological Agents

To examine the safety and efficacy of mirabegron as 'add-on' therapy to solifenacin in patients with overactive bladder (OAB).. This multicentre, open-label, phase IV study enrolled patients aged ≥20 years with OAB, as determined by an OAB symptom score (OABSS) total of ≥3 points and an OABSS Question 3 score of ≥2 points, who were being treated with solifenacin at a stable dose of 2.5 or 5 mg once daily for at least 4 weeks. Study duration was 18 weeks, comprising a 2-week screening period and a 16-week treatment period. Patients meeting eligibility criteria continued to receive solifenacin (2.5 or 5 mg once daily) and additional mirabegron (25 mg once daily) for 16 weeks. After 8 weeks of treatment, the mirabegron dose could be increased to 50 mg if the patient's symptom improvement was not sufficient, if he/she was agreeable to the dose increase, and the investigator judged that there were no safety concerns. Safety assessments included adverse events (AEs), laboratory tests, vital signs, 12-lead electrocardiogram, QT corrected for heart rate using Fridericia's correction (QTcF) interval and post-void residual (PVR) volume. Efficacy endpoints were changes from baseline in OABSS total score, OAB questionnaire short form (OAB-q SF) score (symptom bother and total health-related quality of life [HRQL] score), mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean number of urinary incontinence (UI) episodes/24 h, mean number of urgency UI episodes/24 h, mean volume voided/micturition, and mean number of nocturia episodes/night. Patients were instructed to complete the OABSS sheets at weeks -2, 0, 8 and 16 (or at discontinuation), OAB-q SF sheets at weeks 0, 8 and 16 (or at discontinuation) and patient voiding diaries at weeks 0, 4, 8, 12 and 16 (or at discontinuation).. Overall incidence of drug-related treatment-emergent AEs (TEAEs) was 23.3%. Almost all TEAEs were mild or moderate. The most common TEAE was constipation, with similar incidence in the groups receiving a dose increase to that observed in the groups maintained on the original dose. Changes in PVR volume, QTcF interval, pulse rate and blood pressure were not considered to be clinically significant and there were no reports of urinary retention. Significant improvement was seen for changes in efficacy endpoints from baseline to end of treatment (EOT) in all groups (patients receiving solifenacin 2.5 or 5 mg + mirabegron 25 or 50 mg).. Add-on therapy with mirabegron 25 mg once daily for 16 weeks, with an optional dose increase to 50 mg at week 8, was well tolerated in patients with OAB treated with solifenacin 2.5 mg or 5 mg once daily. There were significant improvements from baseline to EOT in OAB symptoms with combination therapy with mirabegron and solifenacin. Add-on therapy with mirabegron and an antimuscarinic agent, such as solifenacin, may provide an attractive therapeutic option.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To understand how improvements in the symptoms of overactive bladder (OAB) seen with the β3-adrenoceptor agonist mirabegron 50 mg, correlate with patient experience as measured by validated and standard patient-reported outcomes (PROs), and to identify whether there is overall directional consistency in the responsiveness of PROs to treatment effect.. In a post hoc analysis of pooled data from three randomized, double-blind, placebo-controlled, 12-week Phase III trials of mirabegron 50 mg once daily, responder rates for incontinence frequency (≥50 % reduction in incontinence episodes/24 h from baseline to final visit), micturition frequency (≤8 micturitions/24 h at final visit), and PROs [minimally important differences in patient perception of bladder condition (PPBC) and subsets of the overactive bladder questionnaire (OAB-q) measuring total health-related quality of life (HRQoL), and symptom bother] were evaluated individually and in combination.. Mirabegron 50 mg demonstrated greater improvement from baseline to final visit than placebo for each of the responder analyses, whether for individual objective and subjective outcomes or combinations thereof. These improvements versus placebo were statistically significant for all double and triple responder analyses and for all single responder analyses except PPBC. PRO measurements showed directional consistency and significant correlations, and there were also significant correlations between objective and subjective measures of efficacy.. The improvements in objective measures seen with mirabegron 50 mg translate into a meaningful clinical benefit as evident by the directional consistency seen in HRQoL measures of benefit.

Topics: Acetanilides; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

To investigate the effects of mirabegron (50 mg once daily for 12 weeks) in treatment-naïve women with overactive bladder (OAB) based on urodynamic studies.. This was an open-labeled, single-center, prospective study involving 65 recruited outpatients. The OAB symptom score was used for assessing the severity of subjective symptoms. Urodynamic studies, including uroflowmetry, cystometry, and pressure flow study, were conducted to evaluate objective symptoms. The first desire to void, maximum cystometric capacity, and occurrence of detrusor overactivity were measured as storage function parameters, whereas maximum flow rate, detrusor pressure at Qmax, and postvoid residual urine volume were assessed as voiding function parameters.. A total of 60 patients with a mean age of 72.3 years (50-86 years) were included in the analysis. The subjective symptom parameter (ie, the mean OAB symptom score) decreased significantly from 9.4 to 6.2 points (P <.001). In objective symptom parameters, both the first desire to void and maximum cystometric capacity significantly improved after treatment, and detrusor overactivity disappeared in 14 of 35 patients (40.0%) compared with that at baseline (P <.01). The voiding function parameters (ie, mean maximum flow rate, detrusor pressure at Qmax, and postvoid residual urine volume) did not significantly change, demonstrating that mirabegron does not inhibit voiding function.. Mirabegron improves storage function and subjective symptoms, without influencing voiding function, in women with OAB.

Topics: Acetanilides; Aged; Aged, 80 and over; Female; Humans; Middle Aged; Prospective Studies; Severity of Illness Index; Thiazoles; Urinary Bladder, Overactive; Urination; Urodynamics; Urological Agents

The objective of these studies was to evaluate the pharmacokinetic profile, safety, and tolerability of mirabegron, a β3-adrenoceptor agonist for the treatment of overactive bladder, including food effects (low- or high-fat meals) and sex, in healthy East Asian subjects.. In total, 5 pharmacokinetic studies of mirabegron were conducted in healthy East Asian subjects. Food effects were assessed in 3 randomized, single-dose studies in young Japanese male subjects (study 1), male and female subjects (study 2), and young Taiwanese male and female subjects (study 3). In the other 2 single- and multiple-dose studies in young Chinese male and female subjects (study 4 and study 5), mirabegron was administered as a single dose under fasted conditions. After the washout period, mirabegron was administered once daily under fed conditions for 8 days. Pharmacokinetic parameters were determined using noncompartmental methods. Safety and tolerability assessments included physical examinations, vital signs, 12-lead ECG, clinical laboratory tests (biochemistry, hematology, and urinalysis), and adverse event monitoring.. After administration of single oral doses of mirabegron, exposure under fed conditions was lower than under fasted conditions in Japanese and Taiwanese subjects. In Japanese subjects, a greater reduction in mirabegron Cmax and AUC0-∞ was observed after a low-fat meal compared with a high-fat meal. In Chinese subjects, Cmax was reached at approximately 4.0 hours after single oral doses. Mirabegron accumulated 2- to 3-fold on once-daily dosing of multiple-dose relative to single-dose data. Steady state was reached within 7 days. After administration of mirabegron, mean values for Cmax and AUC in female subjects were higher than those in male subjects. Mirabegron was well tolerated in Japanese, Taiwanese, and Chinese subjects.. Our studies confirm the higher exposure levels of mirabegron in female compared with male East Asian subjects as found earlier in Western subjects. Furthermore, the effects of food on the pharmacokinetic profiles appeared to be similar among the 3 populations tested in our studies. The findings suggest that there are no significant pharmacokinetic differences among the Japanese, Taiwanese, and Chinese populations.

Topics: Acetanilides; Administration, Oral; Adrenergic beta-3 Receptor Agonists; Adult; Area Under Curve; Asian People; Eating; Fasting; Female; Healthy Volunteers; Humans; Male; Sex Factors; Thiazoles; Urinary Bladder, Overactive; Urological Agents; Young Adult

To evaluate the efficacy and safety of the β3 -adrenoceptor agonist, mirabegron, compared with placebo in Japanese patients with overactive bladder (OAB).. Patients with OAB symptoms for ≥24 weeks, ≥8 micturitions/24 h on average, and ≥1 episode of urgency and/or urgency incontinence/24 h were randomized to mirabegron (25, 50 or 100 mg) or placebo for 12 weeks. The primary endpoint was change from baseline to end of study in the mean number of micturitions/24 h. Secondary endpoints included micturition variables related to urgency, incontinence, volume voided, and quality of life based on the King's Health Questionnaire (KHQ). Safety was evaluated based on adverse events (AEs), laboratory findings, vital signs, electrocardiogram, and post-void residual volume.. In total, 842 patients were randomized to placebo (n = 214), mirabegron 25 mg (n = 211), 50 mg (n = 208), or 100 mg (n = 209). The primary endpoint was significantly improved in each mirabegron group compared with placebo (P < 0.001; Williams' multiple comparison test). The maximal efficacy in the primary endpoint was observed at the 50 mg dose. Significant improvements were also observed in incontinence, urgency incontinence, mean volume voided, and 3 of the 9 domains from the KHQ (incontinence impact, physical limitations, and severity measures) at each mirabegron dose. Urgency episodes decreased, and mean volume voided increased, dose-dependently. The incidence of AEs in each mirabegron dose was comparable with placebo.. Mirabegron demonstrated significant improvements in OAB symptoms compared with placebo and was well tolerated.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Japan; Male; Middle Aged; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Mirabegron is a potent and selective β3-adrenoceptor agonist developed for the treatment of overactive bladder. In vitro studies demonstrated that mirabegron partly acts as a (quasi-) irreversible, metabolism-dependent inhibitor of CYP2D6. The effect of steady-state mirabegron on single doses of the sensitive CYP2D6 substrates metoprolol (100 mg) and desipramine (50 mg) was assessed in two open-label, one-sequence crossover studies in healthy subjects (CYP2D6 extensive metabolizers). Mirabegron 160 mg/day increased metoprolol maximum plasma concentration (C max) 1.90-fold (90 % confidence interval [CI] 1.54; 2.33) and total exposure (AUC0-∞) 3.29-fold (90 % CI 2.70; 4.00) in 12 males (study 1). Mean metoprolol half-life increased from 2.96 to 4.11 h. α-Hydroxymetoprolol C max and AUC to last measurable concentration decreased 2.6-fold and 2.2-fold, respectively. In study 2, mirabegron 100 mg/day increased desipramine C max 1.79-fold (90 % CI 1.69; 1.90) and AUC0-∞ 3.41-fold (90 % CI 3.07; 3.80) in 14 males and 14 females. Mean desipramine half-life increased from 19.5 to 35.8 h. C max of 2-hydroxydesipramine decreased ~twofold, while AUC increased ~1.3-fold. Desipramine was administered again 2 weeks after the last mirabegron dose. Desipramine C max and AUC0-∞ were still ~1.13-fold increased; the 90 % CIs fell within the 0.80-1.25 interval. All treatments were well tolerated. In conclusion, mirabegron is a moderate CYP2D6 inhibitor (ratio and 90 % CI <5.0).

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Adult; Area Under Curve; Cross-Over Studies; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Desipramine; Drug Interactions; Enzyme Inhibitors; Female; Half-Life; Healthy Volunteers; Humans; Male; Metabolic Clearance Rate; Metoprolol; Middle Aged; Thiazoles; Urinary Bladder, Overactive; Young Adult

Mirabegron is a human β3-adrenoceptor agonist for the treatment of overactive bladder. The pharmacokinetic profile of mirabegron has been extensively characterized in healthy Caucasian subjects.. The objective of this study was to evaluate the pharmacokinetics, dose-proportionality, and tolerability of mirabegron following single and multiple oral doses in healthy Japanese male subjects. The results were compared with those reported in non-Japanese (primarily Caucasian) subjects.. Two studies were conducted. In a single-blind, randomized, placebo-controlled, parallel-group, single- and multiple-ascending dose study (Study 1), mirabegron oral controlled absorption system (OCAS) tablets were administered at single doses of 50, 100, 200, 300, and 400 mg, with eight subjects (six active, two placebo) per dose group (Part I), and once daily for 7 days at 100 and 200 mg with 12 subjects (eight active, four placebo) per group (Part II). In an open-label, three-period, single-ascending dose study (Study 2), mirabegron OCAS was administered to 12 subjects at 25, 50, and 100 mg in an intra-subject dose-escalation design. Plasma and/or urine samples were collected up to 72 h after the first and last dose and analyzed for mirabegron. Pharmacokinetic parameters were determined using non-compartmental methods. Tolerability assessments included physical examinations, vital signs, 12-lead electrocardiogram, clinical laboratory tests (biochemistry, hematology, and urinalysis), and adverse event (AE) monitoring.. Forty and 24 young male subjects completed Part I and II, respectively, of Study 1. Twelve young males completed Study 2. After single oral doses (25-400 mg), maximum plasma concentrations (C max) were reached at approximately 2.8-4.0 h postdose. Plasma exposure (C max and area under the plasma concentration-time curve) of mirabegron increased more than dose proportionally at single doses of 25-100 mg and approximately dose proportionally at high doses of 300 and 400 mg. A more than dose proportional increase in plasma exposure was noted in the body of the same individual. Mirabegron accumulated twofold upon once-daily dosing relative to single-dose data. Steady state was reached within 7 days. Mirabegron was generally well-tolerated at single doses up to 400 mg and multiple doses up to 200 mg. The AE with the highest incidence was increased pulse rate at 400 mg in Study 1.. Mirabegron OCAS exhibits similar single- and multiple-dose pharmacokinetic characteristics and deviations from dose proportionality in healthy Japanese male subjects compared with those observed in non-Japanese (primarily Caucasian) subjects in previous studies.

Topics: Acetanilides; Adrenergic Agonists; Adult; Asian People; Dose-Response Relationship, Drug; Healthy Volunteers; Humans; Japan; Male; Single-Blind Method; Thiazoles; Urinary Bladder, Overactive; Young Adult

To evaluate the efficacy and safety of the β3-adrenoceptor agonist mirabegron, in a Japanese population with overactive bladder (OAB).. This randomised, double-blind, placebo-controlled phase III study enrolled adult patients experiencing OAB symptoms for ≥24 weeks. Patients with ≥ 8 micturitions/24 h and ≥1 urgency episode/24 h or ≥1 urgency incontinence episode/24 h were randomised to once-daily placebo, mirabegron 50 mg or tolterodine 4 mg (as an active comparator, without testing for non-inferiority of efficacy and safety) for 12 weeks. The primary endpoint was the change in the mean number of micturitions/24 h from baseline to final assessment. Secondary endpoints included micturition variables related to urgency and/or incontinence and quality-of-life domain scores on the King's Health Questionnaire. Safety assessments included adverse events (AEs), post-void residual urine volume, laboratory variables, vital signs and 12-lead electrocardiogram.. A total of 1139 patients were randomised to receive placebo (n = 381), mirabegron 50 mg (n = 380) or tolterodine 4 mg (n = 378). Demographic and baseline characteristics were similar among the treatment groups. At final assessment, mirabegron was significantly superior to placebo in terms of mean [sd] change from baseline in number of micturitions/24 h (-1.67 [2.212] vs -0.86 [2.354]; P < 0.001) and mean [sd] change from baseline in number of urgency episodes/24 h (-1.85 [2.555] vs -1.37 [3.191]; P = 0.025), incontinence episodes/24 h (-1.12 [1.475] vs -0.66 [1.861]; P = 0.003), urgency incontinence episodes/24 h (-1.01 [1.338] vs -0.60 [1.745]; P = 0.008), and volume voided/micturition (24.300 [35.4767] vs 9.715 [29.0864] mL; P < 0.001). The incidence of AEs in the mirabegron group was similar to that in the placebo group. Most AEs were mild and none were severe.. Mirabegron 50 mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Asian People; Benzhydryl Compounds; Cresols; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

To evaluate the safety and tolerability of the β3 -adrenoceptor agonist, mirabegron, in patients with overactive bladder (OAB).. Tolerability and safety data from three 12-week, randomised, placebo-controlled, double-blind, Phase III trials (Studies 046, 047 and 074) were pooled by treatment group. The three studies were of a similar design, although the assessed doses of mirabegron [25, 50 or 100 mg once daily (qd)] varied, and tolterodine extended release (ER) 4 mg was included as an active-control arm in Study 046 only. Tolerability and safety data from a 1-year, randomised, double-blind, Phase III trial (Study 049) are also presented. Safety variables included the incidence and severity of treatment-emergent adverse events (TEAEs), vital signs and electrocardiogram data.. Mirabegron (25, 50 or 100 mg qd) was safe and well-tolerated in patients with OAB over 12-week (n = 2736) and 1-year (n = 1632) periods. The incidence of TEAEs and treatment discontinuations as a result of TEAEs was low; the majority were mild in severity and few were serious. Hypertension, nasopharyngitis and urinary tract infection were the most common TEAEs with mirabegron. The mirabegron tolerability profile was similar to that seen with placebo and tolterodine ER 4 mg, except for dry mouth, which occurred, on average, five times less frequently with mirabegron than tolterodine ER 4 mg. In the pooled 12-week analysis, mirabegron 50 mg was associated with placebo-adjusted mean increases of 0.4-0.6 mmHg in blood pressure and approximately one beat per minute in pulse rate, both reversible upon treatment discontinuation. The incidence of Major Adverse Cardiovascular Events as adjudicated by an independent cardiovascular committee was low and similar across treatment groups.. The favourable tolerability profile of mirabegron in patients with OAB may allow improved treatment compliance compared with antimuscarinics, with important implications for patient outcomes.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Antagonists; Adult; Aged; Aged, 80 and over; Double-Blind Method; Drug Tolerance; Female; Humans; Male; Middle Aged; Off-Label Use; Placebos; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

The aim of the present review article was to summarize the efficacy and tolerability for mirabegron 50 mg over 12 weeks and 1 year versus placebo (SCORPIO) or tolterodine ER 4 mg (SCORPIO and TAURUS). After a 2-week placebo run-in, adults with overactive bladder symptoms for ≥3 months were randomized if, during a 3-day micturition diary period before baseline, they had an average of ≥8 micturitions/24 h and ≥3 urgency episodes. Efficacy end-points were change from baseline to each study visit and final visit in incontinence, micturitions, volume voided/micturition, urgency incontinence, urgency (grades 3 or 4), level of urgency and nocturia. Additional secondary efficacy variables included patient-reported outcomes. Safety variables included changes in treatment-emergent adverse events and vital signs. For SCORPIO, statistically significant improvements from baseline in efficacy variables and patient-reported outcomes were seen with mirabegron versus placebo from week 4, and were maintained over time. For TAURUS, numerical improvements in efficacy were evident from month 1, and were maintained throughout 12 months. Treatment-emergent adverse events incidence was similar between groups, except for dry mouth, which was reported by fourfold (SCORPIO) and threefold (TAURUS) more patients taking tolterodine than mirabegron. Mirabegron 50 mg for 12 weeks was associated with statistically significant improvements in objective measures of efficacy and patient-reported outcomes. At final visit, improvements with mirabegron 50 mg were statistically greater versus placebo. The efficacy profile of mirabegron 50 mg appears to be maintained over 12 months.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Drug Administration Schedule; Female; Headache; Humans; Hypertension; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Retention; Urinary Tract Infections; Urination; Xerostomia

To evaluate the potential of mirabegron, a selective β3-adrenoceptor agonist, for treatment of overactive bladder (OAB) symptoms.. A multicenter, randomized, double-blind, double-dummy, parallel group, placebo and active-controlled, Phase 2, proof-of-concept study was conducted. Eligible patients (n = 314) were enrolled into a single-blind, 2-week placebo run-in period followed by a randomized, double-blind, placebo-controlled treatment period. Patients received mirabegron 100 or 150 mg twice-daily (BID), placebo or tolterodine 4 mg extended release (ER) once-daily for 4 weeks. Primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes per 24 hr. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes per 24 hr; severity of urgency; nocturia, and quality of life measures. Safety parameters included adverse events, laboratory tests, electrocardiogram parameters and post-void residual volume.. Mirabegron 100 and 150 mg BID resulted in a statistically significant improvement versus placebo in mean change from baseline to end-of-treatment in the primary endpoint of micturition frequency (2.2 micturitions/24 hr vs. 1.2 micturitions/24 hr for both doses, adjusted P ≤ 0.01 for both comparisons). Mirabegron had a statistically significant effect versus placebo for most secondary endpoints, including quality of life variables. Despite a small increase in pulse rate, mirabegron demonstrated good safety and tolerability.. Mirabegron was efficacious and well tolerated in patients with OAB symptoms and heralds the first of a new class of oral pharmacological therapy for OAB for more than 30 years.

Topics: Acetanilides; Adult; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Nocturia; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urination; Urological Agents

Mirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder.. Patients completed a single-blinded, 2-week placebo run-in period followed by 12 weeks of randomized (n = 928) double-blinded treatment with mirabegron oral controlled absorption system (OCAS) 25, 50, 100, or 200 mg once-daily (QD), placebo or tolterodine extended release (ER) 4 mg QD. The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24 h. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes/24 h; severity of urgency; nocturia; and quality of life measures. Safety parameters included vital signs, adverse events, laboratory tests, electrocardiogram measurements and post-void residual volume.. Mirabegron 25, 50, 100, and 200 mg resulted in dose-dependent reductions (improvements) from baseline to end-of-treatment in micturition frequency of 1.9, 2.1, 2.1, and 2.2 micturitions/24 h respectively, versus 1.4 micturitions/24 h with placebo (p ≤ 0.05 for the mirabegron 50-, 100-, and 200-mg comparisons). There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables. While there was a significant (p < 0.05) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups, this was not associated with an increased incidence of cardiovascular adverse events.. The favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Incidence; Internationality; Male; Middle Aged; Quality of Life; Single-Blind Method; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To assess the efficacy and tolerability of mirabegron 25 mg and 50 mg once-daily vs placebo in patients with overactive bladder (OAB).. Patients ≥18 years with OAB symptoms were recruited to a 2-week, single-blind, placebo run-in. Those with ≥8 micturitions per 24 hours and ≥3 urgency episodes were randomized 1:1:1 to once-daily mirabegron 25 mg or 50 mg, or placebo for 12 weeks. Primary endpoints were changes to final visit in mean number of incontinence episodes and micturitions per 24 hours. Key secondary endpoints were changes to final visit in mean volume voided or micturition, change to week 4 in mean number of incontinence episodes and micturitions per 24 hours, changes to final visit in mean level of urgency, number of urgency incontinence episodes, and urgency (grade 3 or 4) episodes per 24 hours. Patient-reported outcomes were assessed using the OAB-questionnaire, Patient Perception of Bladder Condition, and Treatment-Satisfaction-Visual Analog Scale.. Both mirabegron groups demonstrated statistically significant improvements in coprimary endpoints vs placebo. Mirabegron 50 mg demonstrated significantly greater improvements vs placebo in the following: change to final visit in mean volume voided per micturition and change to week 4 in mean number of incontinence episodes per 24 hours. Statistically significant improvements vs placebo were demonstrated by mirabegron 50 mg in all patient-reported outcome scales with no increase in the incidence of treatment-emergent adverse events vs placebo.. Mirabegron 25 mg and 50 mg were associated with significant improvements in efficacy measures of incontinence episodes and micturition frequency. Mirabegron was well tolerated vs placebo.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Double-Blind Method; Female; Headache; Humans; Hypertension; Male; Middle Aged; Severity of Illness Index; Tachycardia; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence, Urge

Antimuscarinic agents are currently the predominant treatment option for the clinical management of the symptoms of overactive bladder (OAB). However, low rates of persistence with these agents highlight the need for novel, effective and better-tolerated oral pharmacological agents. Mirabegron is a β3-adrenoceptor agonist developed for the treatment of OAB, with a mechanism of action distinct from that of antimuscarinics. In a randomized, double-blind, placebo- and active-controlled Phase 3 trial conducted in Europe and Australia (NCT00689104), mirabegron 50 mg and 100 mg resulted in statistically significant reductions from baseline to final visit, compared with placebo, in the co-primary end points - mean number of incontinence episodes/24 h and mean number of micturitions/24 h. We conducted a post hoc, subgroup analysis of this study in order to evaluate the efficacy of mirabegron in treatment-naïve patients and patients who had discontinued prior antimuscarinic therapy because of insufficient efficacy or poor tolerability.. Patients were randomized to placebo, mirabegron 50 or 100 mg, or tolterodine extended release (ER) 4 mg orally, once-daily, for 12 weeks. For the post hoc analysis, the primary patient population was divided into the following subgroups: (1) patients who had not received any prior antimuscarinic OAB medication (treatment-naïve) and (2) patients who had received prior antimuscarinic OAB medication. The latter subgroup was further subdivided into patients who discontinued due to: (3) insufficient efficacy or (4) poor tolerability. Analysis of the co-primary efficacy endpoints by subgroup was performed using analysis of covariance with treatment group, subgroup, sex, geographical region, and subgroup-by-treatment interaction as fixed factors; and baseline value as a covariate.. Mirabegron, 50 mg and 100 mg once-daily, demonstrated similar improvements in the frequency of incontinence episodes and micturitions in OAB patients who were antimuscarinic-naïve and who had discontinued prior antimuscarinic therapy. While mirabegron demonstrated improvements in incontinence and micturition frequency in patients who had discontinued prior antimuscarinic therapy due to insufficient efficacy, the response to tolterodine was similar to that of placebo.. In this post hoc subgroup analysis, mirabegron provided treatment benefits in OAB patients who were antimuscarinic treatment-naïve and in patients who had received prior antimuscarinic treatment.

Topics: Acetanilides; Aged; Aged, 80 and over; Australia; Dose-Response Relationship, Drug; Europe; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Prevalence; Retrospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Many patients with overactive bladder discontinue pharmacotherapy due to suboptimal efficacy or side effects. Mirabegron, a β3-adrenoceptor agonist, may offer an effective and well tolerated alternative treatment for overactive bladder.. A randomized, double-blind, placebo controlled trial was conducted in the United States and Canada. After a 2-week placebo run-in period, adults with overactive bladder symptoms for 3 or more months were randomized 1:1:1 to receive placebo, 50 or 100 mg mirabegron once daily for 12 weeks. Efficacy data were collected via patient completed diaries and quality of life assessments. Co-primary efficacy end points were changes from baseline to final visit in mean number of incontinence episodes per 24 hours and micturitions per 24 hours. Key secondary micturition and incontinence end points were also evaluated. Safety assessments included treatment emergent adverse events, laboratory assessments, vital signs, electrocardiograms and post-void residual volume.. Compared to placebo, 50 and 100 mg mirabegron groups demonstrated statistically significantly greater mean decreases (95% CI) from baseline for incontinence episodes (-1.13 [-1.35, -0.91], -1.47 [-1.69, -1.25] and -1.63 [-1.86, -1.40]) and micturitions (-1.05 [-1.31, -0.79], -1.66 [-1.92, -1.40] and -1.75 [-2.01, -1.48]) per 24 hours (p <0.05). Significant improvements in all key secondary end points were observed for both mirabegron doses vs placebo. The incidence of frequently reported treatment emergent adverse events (hypertension, urinary tract infection, headache, nasopharyngitis) was similar in the mirabegron and placebo groups. Dry mouth was reported for 1.5%, 0.5% and 2.1% of patients in the placebo, 50 and 100 mg mirabegron groups, respectively.. Once daily mirabegron in a 50 or 100 mg dose is an effective treatment for overactive bladder symptoms with a low occurrence of side effects.

Topics: Acetanilides; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Receptors, Adrenergic, beta-3; Thiazoles; Urinary Bladder, Overactive

Mirabegron, a β(3)-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB).. To assess the efficacy and tolerability of mirabegron versus placebo.. Multicenter randomised double-blind, parallel-group placebo- and tolterodine-controlled phase 3 trial conducted in 27 countries in Europe and Australia in patients ≥ 18 yr of age with symptoms of OAB for ≥ 3 mo.. After a 2-wk single-blind placebo run-in period, patients were randomised to receive placebo, mirabegron 50mg, mirabegron 100mg, or tolterodine extended release 4 mg orally once daily for 12 wk.. Patients completed a micturition diary and quality-of-life (QoL) assessments. Co-primary efficacy end points were change from baseline to final visit in the mean number of incontinence episodes and micturitions per 24h. The primary comparison was between mirabegron and placebo with a secondary comparison between tolterodine and placebo. Safety parameters included adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, and postvoid residual volume.. A total of 1978 patients were randomised and received the study drug. Mirabegron 50-mg and 100-mg groups demonstrated statistically significant improvements (adjusted mean change from baseline [95% confidence intervals]) at the final visit in the number of incontinence episodes per 24h (-1.57 [-1.79 to -1.35] and -1.46 [-1.68 to -1.23], respectively, vs placebo -1.17 [-1.39 to -0.95]) and number of micturitions per 24h (-1.93 [-2.15 to -1.72] and -1.77 [-1.99 to -1.56], respectively, vs placebo -1.34 [-1.55 to -1.12]; p<0.05 for all comparisons). Statistically significant improvements were also observed in other key efficacy end points and QoL outcomes. The incidence of treatment-emergent AEs was similar across treatment groups. The main limitation of this study was the short (12-wk) duration of treatment.. Mirabegron represents a new class of treatment for OAB with proven efficacy and good tolerability. TRIAL IDENTIFICATION: This study is registered at ClinicalTrials.gov, identifier NCT00689104.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Australia; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Europe; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Single-Blind Method; Surveys and Questionnaires; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urination

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.. To assess the 12-mo safety and efficacy of mirabegron.. Patients ≥ 18 yr of age with OAB symptoms for ≥ 3 mo.. 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 randomized 1:1:1 to once-daily mirabegron 50mg, mirabegron 100mg, or tolterodine extended release (ER) 4 mg for 12 mo.. 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.. A total of 812, 820, and 812 patients received mirabegron 50mg, mirabegron 100mg, 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 -0.5mm Hg for mirabegron 50mg, 100mg, 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.. The safety and tolerability of mirabegron was established over 1 yr, with sustained efficacy observed over this treatment period.. ClinicalTrials.gov identifier: NCT00688688.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Benzhydryl Compounds; Constipation; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Headache; Humans; Hypertension; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Single-Blind Method; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urinary Retention; Xerostomia

To investigate the safety and efficacy of mirabegron for patients with overactive bladder (OAB) that is unresponsive to antimuscarinic agents or is related to benign prostatic hyperplasia (BPH).. Fifty-two newly diagnosed OAB patients (M group) and 45 patients with OAB that was unresponsive to antimuscarinics (S group) received mirabegron 50 mg once daily and were evaluated by OAB symptom score (OABSS), IPSS-QOL index, and IPSS at the time of baseline, 4 and 8 weeks. Newly diagnosed OAB patients treated with antimuscarinic agents were compared as controls.. Mirabegron was effective for 85.2 % in M group. Significant improvements were seen in each domain of OABSS, and there was no significant difference with antimuscarinic therapy. Mirabegron was efficacious for 61.6 % of S group, and significant decreases of OABSS and IPSS-QOL index were observed. Significant improvements were also seen in voiding symptoms in men. Post-void residual urine volumes before and after treatment were 32.1 and 34.8 ml, and 26.2 and 31.3 ml in M and S group, respectively, and there was no significant difference. The incidence of adverse events was 8.4 %, although none were serious, and the patients recovered spontaneously after mirabegron was discontinued.. The present study suggests mirabegron is as effective as antimuscarinics for OAB. It improves OAB symptoms in patients with OAB for which antimuscarinic agents are insufficient. This study revealed that mirabegron improves not only OAB symptoms related to BPH, but also voiding symptoms in men. Low and mild incidences of side effects support the safe utility of mirabegron.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Female; Humans; Male; Muscarinic Antagonists; Prostatic Hyperplasia; Quality of Life; Severity of Illness Index; Thiazoles; Ultrasonography; Urinary Bladder, Overactive; Urodynamics

Mirabegron is a potent and selective β3-adrenoceptor agonist in development for treatment of overactive bladder.. Mirabegron pharmacokinetics after single intravenous (i.v.) and oral doses, absolute bioavailability (F), dose proportionality, sex differences and tolerability were assessed in 2 single-dose, open-label, randomized, parallel-group, cross-over studies in healthy men (exploratory Study 1, n = 12) and men and women (Study 2, n = 91).. After oral dosing (25 - 150 mg), peak plasma concentrations were attained after ~ 4 h. Mean half-life was around 40 h for both routes of administration. Volume of distribution at steady state was 1,670 l and total clearance was around 57 l/h for i.v. dosing. Mirabegron pharmacokinetics were linear after i.v. dosing (7.5 - 50 mg), but exposure increased more than proportionally after oral dosing due to increased F (29% for 25 mg to 45% at 150 mg). About 20% of the (absorbed) dose was excreted unchanged into urine. Area under the curve (AUC) was 27% and 64% higher in females than males after i.v. and oral dosing respectively; differences were mostly attributed to body weight, and for oral dosing, also to F.. Mirabegron pharmacokinetics were linear after i.v. dosing (7.5 - 50 mg), but increased more than proportionally after oral dosing (25 - 150 mg) as a result of increased F. Sex differences in exposure could be explained by body weight and for oral dosing, also by F. Mirabegron was in general well tolerated up to the highest doses studied, 50 mg i.v. and 150 mg oral.

Topics: Acetanilides; Administration, Oral; Adolescent; Adrenergic beta-3 Receptor Agonists; Adult; Area Under Curve; Biological Availability; Biotransformation; Body Weight; Cross-Over Studies; Female; Humans; Infusions, Intravenous; Linear Models; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Netherlands; Sex Factors; Thiazoles; Urinary Bladder, Overactive; Washington; Young Adult

Potential effects of the selective β(3)-adrenoceptor agonist mirabegron on cardiac repolarization were studied in healthy subjects. The four-arm, parallel, two-way crossover study was double-blind and placebo- and active (moxifloxacin)-controlled. After 2 baseline ECG days, subjects were randomized to one of eight treatment sequences (22 females and 22 males per sequence) of placebo crossed over with once-daily (10 days) 50, 100, or 200 mg mirabegron or a single 400-mg moxifloxacin dose on day 10. In each period, continuous ECGs were recorded at two baselines and on the last drug administration day. The lower one-sided 95% confidence interval for moxifloxacin effect on QTcI was >5 ms, demonstrating assay sensitivity. According to ICH E14 criteria, mirabegron did not cause QTcI prolongation at the 50-mg therapeutic and 100-mg supratherapeutic doses in either sex. Mirabegron prolonged QTcI interval at the 200-mg supratherapeutic dose (upper one-sided 95% CI >10 ms) in females, but not in males.

Topics: Acetanilides; Adolescent; Adrenergic beta-Agonists; Adult; Anti-Infective Agents; Aza Compounds; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Fluoroquinolones; Heart Rate; Humans; Long QT Syndrome; Male; Middle Aged; Moxifloxacin; Quinolines; Sex Characteristics; Thiazoles; Urinary Bladder, Overactive; Young Adult

Topics: Drug Therapy, Combination; Fluorometry; Humans; Solifenacin Succinate; Time; Urinary Bladder, Overactive

Representatives of two classes of oral medication are often used to treat urgency urinary incontinence (UUI): solifenacin, an M3-receptor-selective antimuscarinic, and mirabegron, a beta-3 agonist. Two previous asynchronous drug-specific studies suggested different interactions between these medications and the urobiome despite identical methodologies, including recruitment, sample procurement, medication dose escalation strategy, determination of 12-week responders versus nonresponders, and data collection. This analysis compares data from these two studies using a uniform analytic approach.. Urine was collected aseptically via transurethral catheter from consenting participants for subsequent processing by the Expanded Quantitative Urine Culture (EQUC) protocol in two cohorts (n=50 and n=47) that were demographically similar. Species accumulation curves were generated to compare the total number of unique species detected. Indices that measure richness, evenness, and/or abundance were used to compare alpha (within sample) diversity. The Bray-Curtis Dissimilarity Index was used to determine between sample (beta) diversity.. The majority of the 40 species detected in the pre-treatment urobiomes were detected in both cohorts. Both pre-treatment urobiomes were substantially similar in species richness, evenness, and diversity. Differences in pre-treatment urobiomes were associated with treatment response for solifenacin-treated participants only. In contrast, the pre-treatment urobiomes of mirabegron-treated participants were not associated with treatment response. Changes in the post-treatment urobiomes were detected in both cohorts with an increase in richness for both solifenacin (5-mg dose only) and mirabegron.. Pre-treatment urobiome characteristics were associated with treatment response in participants treated with solifenacin, but not mirabegron. Differences exist in urobiome response after treatment with two medications that have known differences in mechanism of action.

Topics: Acetanilides; Adult; Drug Therapy, Combination; Female; Humans; Muscarinic Antagonists; Solifenacin Succinate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Goto-Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and decreased voiding interval and micturition volume. We determined if bladder overactivity could be inhibited by treatment with the combination of a M. Ten-week-old female GK rats were fed a high-fat diet for 4 weeks. Cystometric investigations were conducted at room temperature (RT, 27 ± 2°C). The rats were then intraperitoneally administered the vehicle, the M. After transfer from RT to LT, both voiding interval and bladder capacity of the vehicle-, solifenacin-, or mirabegron-treated rats were significantly decreased. However, the combination of solifenacin and mirabegron significantly mitigated the bladder overactivity. While both M. The cold stress-induced bladder overactivity was not improved by either the M

Topics: Adrenergic Agonists; Adrenergic beta-3 Receptor Agonists; Animals; Cold-Shock Response; Diabetes Mellitus, Type 2; Female; Muscarinic Antagonists; Quality of Life; Rats; Receptors, Adrenergic; Receptors, Muscarinic; RNA, Messenger; Solifenacin Succinate; Urinary Bladder; Urinary Bladder, Overactive

To assess the economic impact associated with overactive bladder (OAB) patients, treated with mirabegron or antimuscarinics (AM) in Spain, over a 12-month period.. A probabilistic model (second-order Monte Carlo simulation) was used in a hypothetical cohort of 1000 patients with OAB and a time horizon of 12 months. The use of resources was obtained from the retrospective observational study MIRACAT that included 3330 patients with OAB. The analysis was carried out from the perspective of the National Health System (NHS) including that of society with the indirect cost of abseenteism in a sensitivity analysis. Unit costs were obtained from Spanish public healthcare prices (€ 2021) and from previously published Spanish studies.. The annual average savings for the NHS for each patient with OAB treated with mirabegron would be € 1135 (95%confidence interval (CI) € 390; 2421) compared with a patient treated with AM. Annual average savings were maintained in all the sensitivity analyses carried out, ranging from a minimum of € 299 to a maximum of € 3381 per patient. The substitution of 25% of the AM treatments (for 81534 patients) to mirabegron would generate, within 1 year, savings for the NHS of € 92 million (95% CI € 31; 197 million).. According to the present model, the treatment of OAB with mirabegron would generate savings compared with treatment with AM in all scenarios and sensitivity analysis performed, and for the NHS and for society perspectives.

Topics: Acetanilides; Humans; Muscarinic Antagonists; Spain; Treatment Outcome; Urinary Bladder, Overactive

To use machine learning algorithms to develop a model to accurately predict treatment responses to mirabegron or antimuscarinic agents in patients with overactive bladder (OAB), using real-world data from the FAITH registry (NCT03572231).. The FAITH registry data included patients who had been diagnosed with OAB symptoms for at least 3 months and were due to initiate monotherapy with mirabegron or any antimuscarinic. For the development of the machine learning model, data from patients were included if they had completed the 183-day study period, had data for all timepoints and had completed the overactive bladder symptom scores (OABSS) at baseline and end of study. The primary outcome of the study was a composite outcome combining efficacy, persistence, and safety outcomes. Treatment was deemed "more effective" if the composite outcome criteria for "successful," "no treatment change," and "safe" were met, otherwise treatment was deemed "less effective." To explore the composite algorithm, a total of 14 clinical risk factors were included in the initial data set and a 10-fold cross-validation procedure was performed. A range of machine learning models were evaluated to determine the most effective algorithm.. In total, data from 396 patients were included (266 [67.2%] treated with mirabegron and 130 [32.8%] treated with an antimuscarinic). Of these, 138 (34.8%) were in the "more effective" group and 258 (65.2%) were in the "less effective" group. The groups were comparable in terms of their characteristic distributions across patient age, sex, body mass index, and Charlson Comorbidity Index. Of the six models initially selected and tested, the decision tree (C5.0) model was chosen for further optimization, and the receiver operating characteristic of the final optimized model had an area under the curve result of 0.70 (95% confidence interval: 0.54-0.85) when 15 was used for the min n parameter.. This study successfully created a simple, rapid, and easy-to-use interface that could be further refined to produce a valuable educational or clinical decision-making aid.

Topics: Acetanilides; Humans; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Overactive bladder (OAB) is a frequent chronic disorder which impairs quality of life by frequent, uncontrollable urination. Newly developed selectiveβ 3-adrenoceptor agonists (sβ 3-agonists) have the same efficacy in treating OAB but significantly fewer side effects than the traditionally used anti-muscarinics. However, safety data on these compounds are scarce. In this study, we analysed the occurrence of adverse effects in patients taking sβ 3-agonists and their characteristics using the JADER database. The most frequently reported adverse effect associated with the use of sβ 3-agonists was urinary retention [mirabegron; crude reporting odds ratios (ROR): 62.1, 95% confidence interval (CI): 52.0-73.6, P<0.001, vibegron; crude ROR: 250, 95% CI : 134-483, P<0.001]. Data from patients with urinary retention were stratified by sex. In both men and women, the rate of urinary retention was higher when using the mirabegron/anti-muscarinic drug when compared to mirabegron monotherapy; its occurrence was higher in men with a history of benign prostatic hypertrophy than in those without. Weibull analysis showed that approximately 50% of sβ 3 agonist-induced urinary retention occurred within 15 days after initiation of treatment, and then gradually decreased. Although sβ 3-agonists are useful against OAB, they may induce several side effects, especially urinary retention, which can further evolve into more severe conditions. Urinary retention occurs more frequently in patients concomitantly taking medication that either increases urethral resistance or has organic factors that block the urethra. When using sβ 3-agonists, the concomitantly used medications and underlying diseases should be thoroughly reviewed, and safety monitoring should be instituted early during the treatment.

Topics: Adrenergic beta-3 Receptor Agonists; Drug-Related Side Effects and Adverse Reactions; East Asian People; Female; Humans; Male; Muscarinic Antagonists; Quality of Life; Receptors, Adrenergic; Treatment Outcome; Urinary Bladder, Overactive; Urinary Retention

Medical treatments for overactive bladder (OAB) have proven efficacy in controlled trials. However, 1-year treatment persistence is reported to be as low as 25% for anticholinergics and 40% for β3 agonists. Real-world data on treatment continuation and treatment sequence is limited. Therefore, we aimed to study treatment persistence trends in women initiated on OAB medications.. We used advanced data-mining techniques to query the largest regional provider's medication purchase database, dispensing for patients, for all women initiating OAB pharmacotherapy between 2010 and 2020. Treatment persistence was measured as days in which the patient was in possession of medication and nonpersistence was defined as prescription nonrefilling for 90 days. We employed a Sankey diagram to explore trends in OAB medication acquisition and treatment sequence. We compared treatment persistence using Kaplan-Meier survival curves and pairwise log-rank analysis.. Here, 46 079 women made 791 681 unique claims of OAB medications. Only 39% of the patients tried more than one OAB formulation, including dose change. The overall persistence rate for all drugs was 55% in 30 days, 46% in 90 days, and 37% per year. The persistence rate for Mirabegron at 30 days was 54%, 42% at 90 days, and 17% at 1 year. Overall, persistence rates were unchanged when stratifying by the time Mirabegron insurance acceptance into coverage (p > 0.05).. Real-world OAB pharmacotherapy persistence rates are lower than previously reported. The introduction of Mirabegron did not seem to improve these rates or affect the treatment sequence.

Topics: Acetanilides; Female; Humans; Muscarinic Antagonists; Prescriptions; Retrospective Studies; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To assess the prescribing practices for overactive bladder (OAB) pharmacotherapy based on the prescription trend analysis across different specialties of India.. s: IQVIA (Quintiles and IMS Health) secondary sales audit (SSA), as well as a prescription audit for antimuscarinics and beta-3 adrenoceptor agonists (mirabegron) from 2014 to 2021, were analyzed. The data includes SSA data of various antimuscarinics like solifenacin, oxybutynin, tolterodine, darifenacin, trospium and mirabegron change in the prescription trend of antimuscarinics and mirabegron across different specialties; prescribers overlap analysis for solifenacin and mirabegron among Indian urologists were also analyzed.. Urologists prescription rates of OAB drugs were 65% in 2016 and 54% in 2021. The rate of OAB medication prescription by non-urologist was highest from the surgeon (11%), followed by gynecologists (9%) and consultant physicians (8%) in 2021. In addition, among OAB medication prescription rates for antimuscarinics were 100% in 2016 and 58% in 2021 whereas for mirabegron, it was 0% in 2016 and 42% in 2021. Solifenacin was most frequently prescribed anticholinergics, followed by oxybutynin, tolterodine, darifenacin, and trospium. The proportion of prescribers of OAB medication among urologists was 38% in 2016 and 33% in 2021. Exclusive prescribers of solifenacin were 748 in 2018 and 739 in 2021 at the urologist, whereas for mirabegron, it was 961 in 2018 and 934 in 2021. The compound annual growth rate for prescription of the last 6 years (from 2016-2021) for solifenacin and mirabegron was -3% and 8% respectively.. Urology remained a top prescribing specialty for OAB drugs, although prescription share increased at surgeon and consultant physician. OAB medicines prescriptions by urologists are shifting from leading antimuscarinic solifenacin to beta-agonist mirabegron. Data from this study will ultimately lead to the OAB medication preference by the specialist that could lead to more advanced OAB management.

Topics: Acetanilides; Humans; Muscarinic Antagonists; Prescriptions; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive; Urological Agents

Mirabegron is a beta-3 adrenergic receptor agonist that received FDA approval in 2021 to treat neurogenic detrusor overactivity (NDO) in children ages three years and older. Despite its safety and efficacy, access to mirabegron frequently remains restricted by payor coverage policies.. This cost minimization study sought to determine the cost implications from a payor perspective of mirabegron use at different points in the treatment pathway for pediatric NDO.. A Markov decision analytic model was constructed to assess the costs for eight treatment strategies over a 10-year period, using six-month cycles (Table). Five strategies involve mirabegron use as first-, second-, third-, or fourth-line therapy. Two strategies, including the "base case," entail use of anticholinergic medications followed by onabotulinum toxin type A (Botox) injection and augmentation cystoplasty. A strategy involving first-line Botox was also modeled. The effectiveness, adverse event rates, attrition rates, and costs associated with each treatment option were obtained from the clinical literature and adjusted to a six-month cycle. Costs were adjusted to 2021-dollar value. A discount rate of 3% was used. To quantify uncertainty, costs and treatment transition probabilities were modeled as gamma and PERT distributions, respectively. One-way sensitivity analyses were performed. Probabilistic sensitivity analysis (PSA) was conducted using a Monte Carlo simulation with 100,000 iterations. Analyses were performed using Treeage Pro (Healthcare Version).. The least costly strategy involved first-line mirabegron (expected cost $37,954). All strategies involving mirabegron were less costly than the base case ($56,417). On PSA, first-line mirabegron was the least costly strategy in 88.9% of cases (mean $37,604, 95% CI: $37,579-37,628); in 100% of cases, the least costly strategy involved mirabegron use. Cost savings associated with mirabegron use were attributable to decreased use of augmentation cystoplasty and Botox injections.. This is the first study to compare costs across multiple strategies involving mirabegron to treat pediatric NDO. Mirabegron use likely yields cost savings for the payor: the least costly strategy involved first-line mirabegron, and all pathways incorporating mirabegron were less costly than those without mirabegron use. These findings provide an updated cost analysis for the treatment of NDO by investigating mirabegron use alongside more established treatment options.. Use of mirabegron for the treatment of pediatric NDO is likely associated with cost savings as compared to treatment pathways without mirabegron. Expansion of payor coverage for mirabegron, as well as clinical studies to study first-line mirabegron use, should be considered.

Topics: Botulinum Toxins, Type A; Child; Costs and Cost Analysis; Humans; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive

Overactive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD.. To assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD.. We employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age ≥65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods.. We identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04-1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses.. Among persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study.

Topics: Acetanilides; Aged; Cholinergic Antagonists; Cohort Studies; Humans; Medicare; Muscarinic Antagonists; Parkinson Disease; Prospective Studies; Treatment Outcome; United States; Urinary Bladder, Overactive; Urological Agents

Mirabegron, commonly known as "Myrbetriq", has been widely prescribed as a medicine for overactive bladder syndrome for over a decade. However, the structure of the drug and what conformational changes it may undergo upon binding its receptor remain unknown. In this study, the authors employed microcrystal electron diffraction (MicroED) to reveal its elusive three-dimensional (3D) structure. They find that the drug adopts two distinct conformational states (conformers) within the asymmetric unit. Analysis of hydrogen bonding and packing demonstrated that the hydrophilic groups are embedded within the crystal lattice, resulting in a hydrophobic surface and low water solubility. Structural comparison revealed the presence of trans- and cis- forms in conformers 1 and 2, respectively. Comparison of the structures of Mirabegron alone with that of the drug bound to its receptor, the beta 3 adrenergic receptor (β3AR) suggests that the drug undergoes major conformational change to fit in the receptor agonist binding site. This research highlights the efficacy of MicroED in determining the unknown and polymorphic structures of active pharmaceutical ingredients (APIs) directly from powders.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Electrons; Humans; Urinary Bladder, Overactive

This study was to investigate urinary beta 3-adrenoceptor concentration as a biomarker for overactive bladder (OAB) and predictor of treatment outcomes in women receiving the beta 3-adrenoceptor agonist mirabegron. The study comprised 50 women identified with OAB and 35 women considered as healthy controls. All women with OAB received daily dosage of 50 mg of mirabegron for 12 weeks. Bladder diaries, OAB-related questionnaires, and global response assessment scale (GRAS) data were collected. Urinary beta 3-adrenoceptor concentration was measured through enzyme-linked immunosorbent assay. All OAB-related questionnaires and GRAS indicated improved posttreatment urinary health. After mirabegron treatment, the frequency of micturition and urgency episodes decreased, but the urinary beta 3-adrenoceptor/creatinine (Cr) ratio increased. The urinary beta 3-adrenoceptor/creatinine ratio was identified as a sensitive biomarker for OAB with a confidence interval of 0.656 to 0.856 (p < 0.001). A negative correlation (- 0.431, p = 0.040) between this biomarker and health-related quality of life (HRQL) scores. The Beta 3-adrenoceptor/Cr levels increased significantly in the treatment-responsive group, while they remained unchanged in the unsatisfactory outcome group. This study shows that 12 weeks of mirabegron treatment improves OAB symptoms and HRQL. Furthermore, urinary beta 3-adrenoceptor concentration may be a diagnostic biomarker for OAB.

Topics: Creatinine; Female; Humans; Quality of Life; Urinary Bladder, Overactive; Urinary Tract

Topics: Acetanilides; Double-Blind Method; Female; Humans; Japan; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence

To investigate if children with daytime urinary incontinence (DUI) and overactive bladder (OAB) refractory to standard urotherapy and medicinal treatment, would experience improvement in symptoms after add-on treatment with transcutaneous electrical nerve stimulation (TENS).. Children were retrospectively enrolled from tertiary referral centers at Aarhus and Aalborg University Hospitals. All data were retrieved from the patients' journals. All children were prescribed TENS as an add-on treatment to the highest-tolerable dose of medicinal treatment in a standardized regime of 2 h a day for around 3 months. Primary endpoints were the number of wet days per week (WDPW) and incontinence episodes per day. Effect of treatment was defined as greater or equal to 50% reduction in the frequency of DUI episodes. Secondary endpoints were to establish predictive factors for the effect of treatment using logistic regression.. Seventy-six children diagnosed with DUI and OAB refractory to treatment with standard urotherapy and pharmacological treatment, at the age of 5-16 years were included from February 2017 to February 2020. A reduction in WDPW (from 6.31 [5.86-6.61] to 4.27 [3.45-4.90], p < 0.05) and incontinence episodes per day (from 2.45 [1.98-2.91] to 1.43 [1.07-1.80], p < 0.05) was observed. Twelve patients became completely dry. At 6 months follow-up, seven of the 12 complete responders had relapsed while five remained dry. A history of constipation before TENS was a predictor of poor treatment response (p = 0.016).. TENS as add-on to anticholinergic treatment seems effective in a number of children with treatment-refractory DUI.

Topics: Acetanilides; Adolescent; Child; Child, Preschool; Cholinergic Antagonists; Diurnal Enuresis; Humans; Retrospective Studies; Thiazoles; Transcutaneous Electric Nerve Stimulation; Treatment Outcome; Urinary Bladder, Overactive

The differential risk of incident dementia associated with receiving various overactive bladder (OAB) drugs is unknown.. To estimate the association of antimuscarinic OAB drug (exposure), compared with a β-3 agonist (mirabegron), and incident dementia.. A population-based nested case-control study was conducted in patients treated with OAB medications in Ontario, Canada. A total of 11 392 patients aged ≥66 yr with a new diagnosis of dementia between 2010 and 2017, and 29 881 age- and sex-matched controls without dementia were included in the study.. Receipt of an antimuscarinic OAB drug or receipt of mirabegron, within the previous 6-12 mo.. Cases developed dementia and Alzheimer's disease. Controls were derived from the general population and matched to cases based on important baseline characteristics. Odds ratios (ORs) for incident dementia, adjusted for demographic and health-related characteristics, were determined.. Patients receiving solifenacin (OR 1.24; 95% confidence interval 1.08-1.43) and darifenacin (OR 1.30; 95% CI 1.08-1.56) in the prior 6 mo had increased odds of incident dementia compared with those receiving mirabegron. In the 6 mo to 1 yr prior to diagnosis, receipt of solifenacin (OR 1.34; 95% CI 1.11-1.60), darifenacin (OR 1.49; 95% CI 1.19-1.86), tolterodine (OR 1.21; 95% CI 1.02-1.45), and fesoterodine (OR 1.39; 95% CI 1.14-1.71) was associated with increased odds of incident dementia compared with receipt of mirabegron. No effect was seen with oxybutynin or trospium. Limitations included misclassification of the outcome and residual confounding associated with the use of health administrative databases.. Older adults receiving solifenacin and darifenacin in the 6 mo prior to diagnosis, and those receiving solifenacin, darifenacin, tolterodine, or fesoterodine in the year prior to diagnosis, have increased odds of incident dementia, compared with those receiving mirabegron. Oxybutynin and trospium were not associated with dementia, likely due to a protopathic bias. Careful drug selection is warranted when treating patients with OAB.. In a large Canadian cohort of patients who developed dementia after starting an overactive bladder (OAB) medication, those taking some anticholinergic medications for OAB have an increased risk of dementia compared with those taking mirabegron.

Topics: Aged; Canada; Case-Control Studies; Dementia; Humans; Muscarinic Antagonists; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

This pilot study aims to assess the short-term efficacy and safety of mirabegron in valve bladder, an important cause of persistent hydronephrosis after successful treatment of posterior urethral valves (PUV).. Twenty-two patients with early valve bladder (no residual PUV; persistent hydronephrosis, wetting and urodynamic evidence of detrusor overactivity) were included. Three subjective parameters: frequency, wetting episodes; patient perception of bladder condition score (PPBC) and four objective parameters: uroflow index (UI = Qave/Qmax), voided volume (VV = voided volume/ expected bladder capacity), maximum filling pressure (P det-max) and society of fetal urology (SFU) hydronephrosis grading were analysed pre- and post-3-month treatment with mirabegron (0.5-1 mg/kg/day). All patients were observed for heart rate, BP, ECG changes during therapy.. There was significant reduction (p = 0.001) in mean frequency (pre 15; post 10), wetting episodes (pre 5; post 2) and PPBC (pre 4; post 3). There was significant improvement (p = 0.01) in mean UI (pre 0.3; post 0.5), VV (pre 0.54; post 0.72), Pdet-max (pre 42; post 25) and hydronephrosis grade (pre 3.5; post 2.2). There were no significant side effects.. This pilot study establishes short-term efficacy and safety of mirabegron in valve bladder with overactivity. Further larger long-term studies are warranted.

Topics: Acetanilides; Child; Humans; Pilot Projects; Thiazoles; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics

Mirabegron is used for treatment of storage symptoms in overactive bladder (OAB) caused by spontaneous bladder smooth muscle contractions. However, owing to limitations in available studies using human tissues, central questions are still unresolved, including mechanisms underlying improvements by mirabegron and its anticontractile effects in the detrusor. Here, we assessed concentration-dependent mirabegron effects on contractions of human detrusor tissues in frequency-response curves and concentration-response curves for different cholinergic and noncholinergic agonists. Detrusor tissues were sampled from patients undergoing radical cystectomy. Contractions were induced by electric field stimulation (EFS) and by cumulative concentrations of cholinergic agonists, endothelin-1, and the thromboxane A

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetanilides; Carbachol; Endothelin-1; Female; Humans; Male; Methacholine Chloride; Muscle Contraction; Muscle, Smooth; Receptors, Adrenergic; Thiazoles; Urinary Bladder, Overactive

The primary aim of this study was to identify high prescribing specialties of overactive bladder (OAB) medications for Medicare Part D beneficiaries, and describe prescribing trends by specialty from 2013 to 2017. The secondary aim was to compare the proportion of medication claims by medication class in each specialty.. We used the Medicare Part D Provider Public Use File to identify the four highest prescribing specialties from 2013 to 2017. We then compared patterns of OAB medication prescription for beneficiaries over 65 years of age between specialties. The number of medication claims, cost, and region were considered. OAB medications were classified as anticholinergic or mirabegron for additional comparison. The primary outcome was the number of OAB medication claims, and the secondary outcome was the proportion of mirabegron claims of all medication claims.. Primary care providers (PCPs), urology, obstetrics and gynecology (OB/GYNs), and other specialties prescribed the most OAB medications. Total claims increased from 4.06 million in 2013 to 4.51 million in 2017. Mirabegron increased from 65,520 to 892,996 claims. PCPs prescribed the most OAB medications. Urologists had the highest proportion of mirabegron prescribing (19.6%), with an increased odds of mirabegron prescribing compared to OBGYNs (aOR 1.18, 95% CI 1.16-1.19). Compared to OBGYNs, PCPs, and other specialties demonstrated decreased odds of prescribing mirabegron (aOR 0.92 with 95% CI 0.91-0.93, and aOR 0.90 with 95% CI 0.88-0.91, respectively).. In Medicare Part D beneficiaries, PCPs prescribed the most OAB medications between 2013 and 2017. Urologists were most likely to prescribe mirabegron.

Topics: Acetanilides; Aged; Cholinergic Antagonists; Humans; Medicare; Thiazoles; Treatment Outcome; United States; Urinary Bladder, Overactive; Urological Agents

Overactive bladder (OAB) negatively impacts patient quality of life and may be associated with high resource use. Our aim was to describe the resource use, costs and persistence associated with mirabegron (MB) or antimuscarinic (AM) treatment in patients with OAB.. Observational retrospective study of medical records in adult patients initiating OAB treatment with MB or AM in Catalonia. Healthcare resource use (visits, hospital stays, tests, medication, absorbent pads) in the first year after treatment initiation was collected. Associated costs were estimated (є, reference year 2019), as well as treatment persistence. Treatment discontinuation was defined as the absence of prescription for at least 45 days or treatment change.. The mean cost per patient (SD) was є 1,640.20 (є 1,227.60) with MB and є 2,159.20 (є 2,264.40) with AM; the associated healthcare resource use cost was lower with MB compared to AM, except for OAB drug costs. Persistence after 12 months of treatment initiation was higher in MB (42.1%) compared to AM (33.0%), as was the median time until treatment discontinuation: 299 (95% CI: 270-328) vs 240 days (95% CI: 230-250).. Lower healthcare resource use was observed with MB compared to AM in the first year of index treatment, resulting in a lower mean direct cost per patient and year, despite its higher acquisition cost. Increased treatment persistence, as well as rational use of available treatments improves OAB management and, in return, patients' quality of life.

Topics: Acetanilides; Adult; Female; Health Care Costs; Humans; Male; Muscarinic Antagonists; Quality of Life; Retrospective Studies; Spain; Thiazoles; Urinary Bladder, Overactive; Urological Agents

We assessed the efficacy and safety of mirabegron, a β. OAB patients aged ≥ 80 years were enrolled in this prospective, single-arm observational study. OAB was diagnosed based on the OAB symptom score (OABSS); i.e., a total score of ≥ 3 points and an urgency score of ≥ 2 points. Patients who received 50 mg mirabegron once daily were evaluated at the baseline and at 4, 8, and 12 weeks. The changes from the baseline in the OABSS, International Prostate Symptom Score (IPSS), OAB questionnaire (OAB-q) score, and Vulnerable Elders Survey (VES-13) score were determined. Adverse events, laboratory tests, 12-lead electrocardiography, the QT interval according to Fridericia's formula (QTcF), uroflowmetry, the post-void residual urine volume (PVR), and the Mini-Mental State Examination (MMSE) score were used to assess safety.. Forty-three patients (median age: 84 years, range: 80-96 years) were examined. They had high rates of comorbidities and polypharmacy. Mirabegron significantly improved in total score of the OABSS, including urgency and urge incontinence. The total IPSS, IPSS quality-of-life (QOL) index, and OAB-q scores also significantly improved. Mirabegron improved in the VES-13 score. There were no significant changes in laboratory test values, uroflowmetry findings, PVR, the QTcF, or MMSE score. Two patients (4.7%) withdrew from the study after experiencing adverse events.. Mirabegron was well tolerated and significantly improved in OAB symptoms, and QOL in older patients. Trial registration The present clinical study was approved by University of Yamanashi Institutional Review Board prior to study initiation (ID1447) and was retrospectively registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (UMIN000045996) on Nov 6, 2021.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged, 80 and over; Female; Frail Elderly; Humans; Japan; Male; Prospective Studies; Quality of Life; Surveys and Questionnaires; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Overactive bladder (OAB) is a common lower urinary tract dysfunction syndrome. A stepwise approach is a prudent choice. Urotherapy is recommended by the International Children's Continence Society (ICCS) as the first-line treatment for OAB.

Topics: Acetanilides; Child; Female; Humans; Male; Pilot Projects; Thiazoles; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive

Mirabegron, a beta-3 agonist, is prescribed for urgency urinary incontinence (UUI). We assessed the correlation of symptom improvement with urobiome characteristics in adult women participants prescribed mirabegron for UUI treatment.. We enrolled participants seeking UUI treatment who selected mirabegron and agreed to participate in this 12-week, open label study conducted at the Female Pelvic Medicine and Reconstructive Surgery Center at Loyola University Medical Center. Following eligibility screening and research consent, participants completed the overactive bladder questionnaire (OAB-Q) and provided a catheterized urine sample at baseline, 4, 8, and 12 weeks. The primary outcome, symptom improvement at 12 weeks, was based on the validated Patient Global Symptom Control questionnaire score to dichotomize symptom response (responder vs nonresponder [PGSC score ≤3]). Urine samples were processed by the Expanded Quantitative Urine Culture (EQUC) protocol.. Eighty-three participants (mean age 68 years) completed baseline assessment. Of the 47 participants with primary outcome data and samples analysis, there were 16 responders and 31 nonresponders; responder groups were similar demographically. Living microbes were detected in most participants. There were no significant differences in alpha diversity (within sample) at baseline between groups. However, at the 12-week follow-up, the responder urobiome became significantly richer, with a larger number of genera (p = 0.027) and was significantly more diverse than the nonresponders.. Longitudinal urobiome changes are associated with symptom improvement in adult women being treated with mirabegron for UUI. The mechanism for symptoms improvement may relate to the detected changes in the urobiome and warrants further study.

Topics: Acetanilides; Adult; Aged; Female; Humans; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

There is no clear pathophysiologic evidence determining how long overactive bladder (OAB) medication should be continued. We, therefore, investigated the effect of mirabegron using cessation (CES) or continuation (CON) treatment in an OAB animal model.. Female C57BL/6 mice were divided into four groups (N = 8 each): Sham, OAB, CES, and CON groups. The OAB-like condition was induced by three times weekly intravesical instillations of KCl mixture with hyaluronidase. After the last intravesical instillation for inducing OAB, mirabegron (2 mg/kg/day) was administered in CES and CON groups for 10 and 20 days, respectively. Final experiments were carried out on 20 days from the last intravesical instillation in all groups. After cystometry, mRNA levels of bladder muscarinic, β-adrenergic, and P2X purinergic receptors were measured to investigate bladder efferent and afferent activity. In addition, mRNA levels of CCL2 and CCR2 in L6-S1 dorsal root ganglia (DRG) were measured to assess afferent sensitization. Immunofluorescent staining of CX3CR1, GFAP, and CCR2 in the L6 spinal cord was also conducted to investigate glial activation and central sensitization.. Continuous mirabegron treatment seems to prevent central sensitization and, thus, might be desirable for long-term disease control of OAB.

Topics: Acetanilides; Animals; Central Nervous System Sensitization; Disease Models, Animal; Female; Mice; Mice, Inbred C57BL; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thiazoles; Urinary Bladder, Overactive

Antimuscarinic (AM) and beta-3-agonist (B3A) treatment are the standard first-line pharmacological treatment used to manage overactive bladder (OAB) patients. Aim of our study was to analyze real-life data of adverse events related to AMs and B3A reported on Eudra-Vigilance (EV) Database.. EV database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of AEs for antimuscarinic and beta-3-agonist per category and severity until January 2021.. Overall, 2313 AEs were reported for oxybutinin, 5129 for solifenacin, 2483 for tolterodine, 3523 for fesoterodine, 787 for trospium, 621 for propiverine and 7213 for mirabegron. Urinary retention was higher for fesoterodine (43%) and tolterodine (23%) when compared to solifenacin (10%), mirabegron (11%) and oxybutinin (4%). Cognitive disorder was uncommon for all the analyzed drugs analyzed. Regarding anticolinergic AEs: vision blurred, dry mouth and constipation were higher for AMs when compared to mirabegron. Their prevalence was higher in female patients. Mirabegron presented a higher risk of hypertension (7%) when compared to oxybutinin (2%, P<0.01), solifenacin (2%, P<0.01), tolterodine (2%, P<0.01) and fesoterodine (1%, P<0.01); the rate of hypertension was higher in females (63%) than males (29%) (P<0.01). The risk of acute urinary retention was also significantly higher (15% vs. 10%, P<0.01) in older patients (>85 years).. Real life data is consistent with registry studies regarding the rate of AEs related to antimuscarinic and beta-3-agonist. However some differences were observed. Female patients present higher rates of AEs when compared to male patients. The risk of acute urinary retention was particularly evident in the octogenarians.

Topics: Aged; Aged, 80 and over; Female; Humans; Hypertension; Male; Muscarinic Antagonists; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Retention

Background and Objectives: To determine changes in the blood pressure (BP) and pulse rate (PR) before and after the administration of mirabegron in real-world clinical practice for patients with overactive bladder (OAB). Materials and Methods: This study was conducted in patients newly diagnosed with OAB. Before and 12 weeks after mirabegron treatment, we evaluated the effects on BP and PR. An overall examination was conducted, and the patients were divided into two groups according to their age: a young group (<65 years old) and an old group (≥65 years old). Results: A total of 263 patients were enrolled in this study. In the overall and intragroup comparisons, the systolic BP (SBP) did not change significantly after mirabegron administration. However, an increase in SBP of ≥10 mmHg was observed in 53 (20.2%), 4 (7.4%), and 49 (23.4%) in the entire group, young group, and old group, respectively (p = 0.009). Regarding diastolic BP, a significant decrease after the treatment was detected in entire (71.2 ± 11.4 versus 69.8 ± 10.7 mmHg; p = 0.041) and old patients (71.5 ± 10.6 versus 69.5 ± 10.2 mmHg; p = 0.012). There was no significant change in PR in our study population. Further examination using a propensity match score revealed that age was the risk factor for the increase in SBP after mirabegron administration. Conclusions: Mirabegron does not have any adverse effects on BP and PR. However, since some patients in this study had elevated SBP after administration, we suggest regular BP monitoring during mirabegron treatment.

Topics: Acetanilides; Aged; Blood Pressure; Heart Rate; Humans; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Evidence to support the effectiveness of β3-adrenoceptor agonist mirabegron and anti-muscarinic solifenacin in the management of bladder dysfunction caused by psychological stress is lacking. This study investigates whether mirabegron or solifenacin reduces the bladder overactivity caused by water avoidance stress (WAS) in mice. Female mice were exposed to WAS for 1 h/day for 10 days and received either placebo, solifenacin or mirabegron in drinking water. Controls were age-matched without stress exposure. Voiding behaviour and functional isolated whole bladder responses during distension and in response to pharmacological agents and electrical field stimulation was investigated. Urinary frequency was significantly increased following stress. Mice treated with mirabegron or solifenacin displayed significantly fewer voiding events compared to the stressed mice, and voiding frequency in drug-treated animals was comparable to unstressed controls. The maximal contractile responses of bladders to carbachol were significantly enhanced by stress and reduced by mirabegron but not solifenacin. The frequency of phasic bladder contractions following stimulation with carbachol was significantly enhanced following stress and remained elevated in the mirabegron treated group. However, treatment with solifenacin significantly reduced the frequency of phasic contractions to unstressed control levels. Solifenacin and mirabegron are beneficial in reducing the overall voiding dysfunction caused by WAS in mice.

Topics: Acetanilides; Animals; Carbachol; Female; Mice; Muscarinic Antagonists; Solifenacin Succinate; Stress, Psychological; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder (OAB) and frailty are independently associated with patient burden. However, economic burden and treatment-taking behavior have not been well characterized among frail patients with OAB, which, given the varying safety and tolerability profiles of available treatments, is crucial.. To assess costs, health care resource utilization, treatment-taking behavior (persistence and adherence) to OAB medication in older, frail OAB patients.. This was a retrospective cohort study using international business machines MarketScan Medicare Supplemental claims data. Eligible frail patients (per Claims-based Frailty Index score) initiating mirabegron were 1:2 propensity score matched (based on age, sex, and other characteristics) with those initiating antimuscarinics and were followed up to 1 year. All-cause, per-person, per-month costs, health care encounters, persistence (median days to discontinuation assessed using Kaplan-Meier methods) and adherence (≥80% of proportion of days covered at Day 365) were compared.. From 2527 patients with incident mirabegron (21%) or antimuscarinic (79%) dispensations, 516 incident mirabegron users (median age: 82 years, 64% female) were matched to 1032 incident antimuscarinic users (median age: 81 years, 62% female). Median cost was higher in mirabegron group ($1581 vs. $1197 per month); this was primarily driven by medication cost. There was no difference in medical encounters. Adherence (39.1% vs. 33.8%) and persistence (103 vs. 90 days) were higher in mirabegron users.. Among frail older adults with OAB, mirabegron use was associated with higher costs and potential improvements in treatment-taking behaviors, particularly with respect to treatment adherence, versus those initiating antimuscarinics.

Topics: Acetanilides; Aged; Aged, 80 and over; Female; Frail Elderly; Frailty; Humans; Male; Medicare; Muscarinic Antagonists; Retrospective Studies; United States; Urinary Bladder, Overactive; Urological Agents

Overactive bladder (OAB) is associated with physical, emotional, and financial burden. After failed conservative measures, second-line therapy includes medications, such as antimuscarinics and beta-3 adrenergic receptor (β3AR) agonists. Antimuscarinics are most commonly prescribed but have systemic side effects that lead to poor compliance. β3AR agonists include mirabegron and vibegron. Mirabegron is a first-generation β3AR agonist that is effective for frequency, urgency urinary incontinence (UUI) and urgency, but has interactions with cytochrome P450 enzymes (CYPs) and cardiovascular sequelae. Vibegron is a second-generation β3AR agonist that is highly selective and does not interact with CYPs. It is effective for reducing UUI episodes and daily micturition number and has a favorable side effect profile.. Clinical background, pharmacology, and clinical studies for vibegron.. Vibegron is a welcomed addition to the OAB therapeutic landscape. This single dose, once daily option is effective, especially for patients with wet OAB, with a favorable side effect profile. Sub-analyses of patients ≥ 65 years have shown continued efficacy and safety. The few drug interactions are of benefit, especially for older patients with polypharmacy. As long-term data accrues, vibegron has the potential to drive the OAB therapeutic market.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Receptors, Adrenergic, beta-3; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Overactive bladder (OAB) is a disease that seriously affects patients' quality of life and mental health. To address this issue, more and more researchers are examining the relationship between OAB treatment and urinary microecology. In this study, we sought to determine whether differences in treatment efficacy were related to microbiome diversity and composition as well as the abundance of specific genera. Machine learning algorithms were used to construct predictive models for urine microbiota-based treatment of OAB.. Urine samples were obtained from 64 adult female OAB patients for 16S rRNA gene sequencing. Patients' overactive bladder symptom scores (OABSS) were collected before and after mirabegron treatment and patients were divided into effective and ineffective groups. The relationship between the relative abundance of certain genera and OABSS were analyzed. Three machine learning algorithms, including random forest (RF), supporting vector machine (SVM) and eXtreme gradient boosting (XGBoost) were utilized to predict the therapeutic effect of mirabegron based on the relative abundance of certain genera in OAB patients' urine microbiome.. The species composition of the two groups differed. For one, the relative abundance of. The results of this study indicate that urinary microbiota might influence the efficacy of mirabegron, and that

Topics: Adult; Female; Gardnerella; Humans; Lactobacillus; Prevotella; Quality of Life; RNA, Ribosomal, 16S; Urinary Bladder, Overactive

Phosphodiesterase type 5 inhibitors (PDE5i) is the only approved oral treatment for erectile dysfunction (ED) in the US, and alternative management remains necessary when this treatment fails or is contraindicated. Targeting other pathways than the NO-cGMP pathway and/or combining this approach with PDE5i may introduce new treatments for men who are unresponsive to PDE5i. This study aims to evaluate whether Mirabegron improves erectile function in men with concurrent overactive bladder and mild to moderate ED. Twenty subjects, 40-70 years old, registering International Index of Erectile Function (IIEF) score 11-25 and International Prostate Symptom Score 8-20, were treated with Mirabegron therapy for 12 weeks. Study participants were re-administered IIEF and OAB-q questionnaires on weeks 2, 4, 8, and 12 and assessed for adverse events. The primary and secondary endpoints were an increase in the IIEF-5 score of 4 units and a decrease in the Overactive Bladder questionnaire (OAB-q) symptom severity score of 10 units between study time points. Thirteen men completed the 12-week study. Mirabegron treatment improved the IIEF-5 scores in five patients (38.4%) by 4 points or more, whereas IIEF-5 scores were not affected by Mirabegron treatment in eight patients (61.5%). There were no clinically relevant decreases in the IIEF-5 score. Significant improvements were observed in intercourse satisfaction at week eight compared to baseline (p = 0.01). Orgasmic function and sexual desire were not affected by Mirabegron treatment. As expected, Mirabegron treatment reduced OAB symptoms based on OAB-q short form (p = 0.006) and OAB-q total health-related quality of life (HRQL) scores compared to baseline (p = 0.03). Residual bladder volumes were not affected by treatment. No serious side effects were reported during the study period. This study suggests that Mirabegron may improve both EF and OAB-related symptoms in some individuals without causing serious adverse events.

Topics: Acetanilides; Adult; Aged; Double-Blind Method; Erectile Dysfunction; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Pilot Projects; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

To descriptively evaluate treatment persistence among adults who received mirabegron or antimuscarinics in South Korea.. This study involved a retrospective analysis of the Health Insurance Review and Assessment (HIRA) database. Patients (≥18 years) who had a new prescription for an overactive bladder (OAB) target medication (mirabegron/antimuscarinic) within an 8-month index period (July 1, 2015-February 29, 2016) were included. The date when the target (index) medication was dispensed was the index date. The 6-month period before the index date was used to assess patient eligibility. A 12-month post-index period was used to assess medication persistence, which was defined as the time to discontinuation. Overall data were analyzed and the results were also stratified by age group (≤65, >65 years), sex, or prior OAB medication experience. Persistence rates were calculated after the 1st, 3rd, 6th, 9th, and 12th months.. A data set of 52 722 cases was obtained (mirabegron: 11 424, antimuscarinics: 41 298). The mean age was 60.9 ± 16.1 years and the majority of the patients were female (30 862 [58.5%] patients). Median persistence was longer with mirabegron (51 days) versus antimuscarinics (25 days). The persistence rate with mirabegron was higher throughout the study compared with all the antimuscarinics (12-month data: 13.5% and 4.9%, respectively). Longer treatment persistence was noted in older, male, and treatment-experienced patients.. The results from the HIRA database showed that persistence was longer with mirabegron than with antimuscarinics in South Korea. This finding may help inform clinical decision-making within the South Korean healthcare system.

Topics: Acetanilides; Adult; Aged; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Republic of Korea; Retrospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Stress-type and urgency-type urinary incontinence are seen together in mixed-type urinary incontinence. Treatment is usually chosen according to the predominant type of incontinence. The aim of this study is to evaluate the effect of mirabegron and duloxetine combination in the treatment of mixed-type urinary incontinence.. The data of 88 mixed-type urinary incontinence patients who applied to the urology outpatient clinic between January 2018 and December 2019 were retrospectively analyzed. We applied mirabegron and duloxetine treatment to the patients. The International Consultation of Incontinence Questionnaire-Short Form, Overactive bladder symptom score questionnaire and daily pad count were statistically evaluated before and after the treatment.. Statistically significant improvements were observed using the questionnaire forms and decreased daily pad usage after the eight-week treatment (p<0.001). Based on the clinical global effect scale, 62.50% of patients had a partial or complete response to treatment and also the use of daily pads were decreased from 3.7-0.89 on an average.. Combination use of mirabegron and duloxetine in the treatment of mixed-type urinary incontinence improved symptom scores and decreased pad usage.

Topics: Acetanilides; Double-Blind Method; Duloxetine Hydrochloride; Humans; Retrospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Urethral instability (URI) has in the past been defined by the International Continence Society (ICS), but was excluded from ICS terminology and definitions shortly after because of a lack of consensus about the clinical importance of this phenomenon. Recently, interest in URI and its possible role in overactive bladder (OAB) increased again. In the last decade, a beta 3 adrenoreceptor agonist (mirabegron) was approved for the treatment of OAB. The effect of mirabegron on urethral pressure during filling cystometry is unknown. The aim of this study was to assess the influence of mirabegron on urethral pressure variations during urodynamic investigation and the association of symptoms and voiding diary data before and during treatment.. This prospective study included 51 consecutive adult female patients, referred with OAB. Patients were evaluated using a voiding diary, two validated questionnaires and two urodynamic investigations, one before and one after 6 weeks of treatment with mirabegron. URI was defined as an urethral pressure drop exceeding 30 cmH. The prevalence of URI was 31% at initial urodynamic investigation, and 19% at second investigation. URI is more common than DO with 18% prevalence at initial evaluation. Treatment with mirabegron resulted in significant changes in symptoms and urodynamic sensory markers in patients with URI.. Urethral pressure variations are significantly reduced by treatment with mirabegron in patients with URI. URI seems to have a predictive value in treatment choices for OAB. Future research should elucidate this.

Topics: Acetanilides; Adult; Female; Humans; Prospective Studies; Sensation; Thiazoles; Urinary Bladder, Overactive; Urodynamics

The aim of this post hoc analysis from the Japanese mirabegron surveillance program was to investigate the safety and effectiveness of mirabegron in male patients with overactive bladder (OAB) symptoms with/without concomitant benign prostatic hyperplasia (BPH).. This 12-week study included patients who were starting mirabegron treatment for the OAB symptoms of urinary urgency, daytime frequency, and urgency urinary incontinence. Patients were stratified according to BPH diagnosis, and patients with BPH were stratified into those who did/did not receive BPH-specific treatment. Assessments included adverse drug reactions (ADRs), residual urine volume evaluations, and total Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score-Quality of Life (IPSS-QoL) measurements.. Of 4540 male patients, 3176 (70.0%) had been diagnosed with BPH. Mean age was slightly higher in patients with BPH (74.7 ± 8.41 years) versus patients without BPH (71.0 ± 12.13 years). Overall, 66/1364 (4.84%), 170/2588 (6.57%), and 35/569 (6.15%) patients without BPH, with BPH + treatment, and with BPH + no treatment, respectively, experienced ≥1 ADR. No patients without BPH and 21/3176 (0.66%) patients with BPH experienced a urinary retention ADR. No significant changes from baseline to week 12 in residual volume were noted. Mirabegron was judged to be an effective treatment for 990/1296 (76.4%) patients without BPH, 1935/2491 (77.7%) patients with BPH + treatment, and 421/538 (78.3%) patients with BPH + no treatment. Significant decreases in total OABSS and IPSS-QoL were observed for all groups.. Mirabegron was a well-tolerated and effective treatment for patients with OAB symptoms with or without BPH in this post-marketing study.

Topics: Acetanilides; Aged; Female; Humans; Male; Prostatic Hyperplasia; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Urological Agents

Topics: Acetanilides; Aged; Cholinergic Antagonists; Dementia; Female; Humans; Insurance Coverage; Middle Aged; Risk; Thiazoles; Urinary Bladder, Overactive; Urological Agents

To assess the clinical, urodynamic efficacy, and safety of mirabegron in patients with neurogenic detrusor overactivity (NDO) consequent to traumatic spinal cord injury (SCI).. This prospective cohort study was performed between January 2018 and July 2019 and included adult patients with stable traumatic suprasacral SCI, performing clean intermittent catheterization (CIC), and demonstrating NDO on urodynamic study (UDS). A 3-day bladder diary was made at the baseline after which all patients were started on Mirabegron 50 mg. They were followed up at 6 weeks with a repeat bladder diary and UDS which were compared with those at the baseline.. A total of 30 patients (4 females, 26 males, mean age: 30.07 years) were included. After 6 weeks of treatment, 5 out of the 29 incontinent patients became completely dry. The mean frequency of CIC decreased from 6.63 at the baseline to 5.37 at 6 weeks (p = .002), the mean CIC volume increased from 275 ml to 341 ml (p = .0002), the mean number of incontinence episodes in between CIC reduced from 3.97 to 2.27 (p < .0001) and time from CIC to leakage increased from 1.73 h to 2.75 h (p < .0001). The mean cystometric capacity increased from 348 ml to 406 ml (p = .008) and the maximum amplitude of NDO decreased from 54 cm H. Mirabegron is efficacious and safe in patients with NDO consequent to traumatic SCI.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Female; Humans; Male; Prospective Studies; Spinal Cord Injuries; Thiazoles; Urinary Bladder, Overactive

Mirabegron (MBN), a β-3 adrenergic agent, is used in the treatment of overactive bladder. MBN has alow water solubility, high first-pass metabolism, and low bioavailability, consequently having poor absorption in the gastrointestinal tract.. The present study is intended to formulate Mirabegron-loaded solid lipid nanoparticles (MBN-SLN) coated with PEG-400 to bypass hepatic first-pass metabolism and to improve its oral bioavailability.. MBN-SLNs were developed using glyceryl monostearate by pre-emulsion-ultrasonication method, which was then optimized applying Box-Behnken Design. The optimized batch of MBN-SLN was selected for surface-modification with PEG-400 (MBN-PEG-SLN) and characterized by photon correlation spectroscopy, DSC, and XRD. Bioavailability studies were conducted in Wistar rats after oral administration of plain MBN dispersion, MBN-SLN, and MBN-PEG-SLN.. Stable MBN-SLNs and MBN-PEG-SLN of the optimized batch having a mean particle size of 162.7 nm and 149.9 nm; zeta potential of -39.1 mV and -30.9 mV; % entrapment of 89.90% and 90.12%, respectively, were developed. The results of the in vitro drug release studies demonstrated a significant slow release of MBN from MBN-SLN (69.38%) and MBN-PEG-SLN (61.33%) as compared to the dispersion of pure drug (92.10%). The relative bioavailability, as a result of the in vivo studies, of MBN from MBN-PEG-SLN increased by 2-fold, based on the Cmax values, in comparison with the plain MBN dispersion.. Thus, the study established that the oral bioavailability of MBN could be improved by the administration of MBN-PEG-SLN. The obtained results indicate SLNs as a potential drug delivery system for improving the bioavailability of poorly bioavailable drugs such as MBN by abating the first-pass metabolism.

Topics: Acetanilides; Animals; Drug Delivery Systems; Lipids; Nanoparticles; Pharmaceutical Preparations; Rats; Rats, Wistar; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Humans; Muscarinic Antagonists; Patient Satisfaction; Personal Satisfaction; Prospective Studies; Thiazoles; Urinary Bladder, Overactive

This post-authorization safety study (EU PAS Register Number: EUPAS16088) was designed to compare the incidence of cancer outcomes in patients treated with mirabegron versus antimuscarinic medications.. Cohorts of mirabegron initiators during 2012-2018 were propensity-score matched to antimuscarinic medication initiators within real-world data sources (Danish National Registers, Swedish National Registers, Clinical Practice Research Datalink [UK], Optum [US], and Humana [US]). Incident cancer cases were identified during follow-up from direct linkage to cancer registers or validated through medical record review or through physician questionnaires. Comparisons of sex-specific composite cancer outcomes (cancer of the lung/bronchus, colon/rectum, melanoma of skin, urinary bladder, non-Hodgkin lymphoma, kidney/renal pelvis, pancreas, prostate in men and breast and uterus in women) were made overall and for person-time in the first year and after the first year following start of treatment, for all ages and for the subgroup ≥65 years.. Among the 80,637 mirabegron initiators matched to 169,885 antimuscarinic medication initiators, 68% were at least 65 years of age and 66% were women. Over 5000 incident cancer cases were observed overall. Incidence rates were higher for men than women for composite and individual cancer outcomes. The pooled fixed effects hazard ratios for composite cancer outcomes (all ages) were 1.05 (95% confidence interval [CI]: 0.98-1.14) for women and 1.06 (95% CI: 0.98-1.14) for men. Results were similar in persons ≥65 years.. The results suggest no association between mirabegron use and risk of cancer, compared with antimuscarinic medications, in either men or women.

Topics: Acetanilides; Female; Humans; Male; Muscarinic Antagonists; Neoplasms; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

The selective

Topics: Acetanilides; Administration, Oral; Adrenergic beta-3 Receptor Agonists; Animals; Brain; Male; Muscarinic Antagonists; Muscle Contraction; Protein Binding; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Submandibular Gland; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive; Urological Agents

Transient receptor potential melastatin 8 (TRPM8) channels may contribute to the pathophysiological bladder afferent hyperactivity, thus a TRPM8 antagonist would be a promising therapeutic target for the bladder hypersensitive disorders including urinary urgency in overactive bladder (OAB). We aimed to investigate a pharmacological effect of KPR-5714, a novel selective TRPM8 antagonist, on TRPM8 channels, M

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Calcium Signaling; Cyclic AMP; Disease Models, Animal; Drug Therapy, Combination; Female; HEK293 Cells; Humans; Muscarinic Antagonists; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-3; Thiazoles; Tolterodine Tartrate; TRPM Cation Channels; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics

To compare the efficacy and tolerability of mirabegron and solifenacin in pediatric patients with idiopathic overactive bladder (OAB) and to identify factors affecting OAB symptom improvement after treatment.. We retrospectively reviewed 103 patients (5-15 years old) who visited our hospital with OAB symptoms between July 2017 and March 2019. All participants had received solifenacin or mirabegron. Those who had secondary OAB or who did not complete the frequency-volume chart either before or after treatment were excluded. The age-adjusted bladder capacity ratio was used to evaluate bladder capacity. Efficacy was assessed on the basis of patient reports and changes in the frequency-volume chart, and ≥90% reduction was regarded as "responding to medication." Tolerability was assessed by obtaining reports from patients about the adverse effects of the drug.. After the exclusion of 58 patients, 45 patients (29 in solifenacin-group and 16 in mirabegron-group) were included in the primary analysis. The age-adjusted bladder capacity ratio increased from 0.71 to 0.96 (p<0.001) and from 0.57 to 0.97 (p=0.002) after solifenacin and mirabegron use, respectively. Decreased bladder capacity before medication was associated with responding to medication (odds ratio, 7.41; p=0.044). There was no significant difference in efficacy between the two drugs. Drug-induced adverse effects were reported in only 3 (10.3%) of the solifenacin-treated patients.. Mirabegron showed comparable efficacy to solifenacin in pediatric patients with idiopathic OAB. Additionally, only few adverse effects were reported, suggesting that mirabegron can be a safe alternative for the treatment of idiopathic pediatric OAB.

Topics: Acetanilides; Adolescent; Age Factors; Child; Child, Preschool; Female; Humans; Male; Retrospective Studies; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

This analysis from the PERSPECTIVE (a Prospective, Non-interventional Registry Study of Patients Initiating a Course of Drug Therapy for Overactive Bladder) study evaluated treatment persistence with mirabegron or antimuscarinics over a 12-month period.. Participants were adults diagnosed with overactive bladder (OAB) by their health care provider (HCP), who were initiating mirabegron or antimuscarinic treatment. The HCP made all treatment decisions, and patients were followed for 12 months with no mandatory scheduled visits. Information requests were sent to patients at baseline and months 1, 3, 6, and 12. Patients were nonpersistent if they switched, discontinued, or added OAB medications/therapies to their initial treatment. Reasons for discontinuation and switching patterns were investigated.. Overall, 1514 patients were included (613 mirabegron and 901 antimuscarinic initiators). Persistence rates decreased steadily over time in both groups. A low proportion of patients added or switched medication at each time point. Unadjusted Kaplan-Meier analysis showed similar persistence rates for both groups. When the data were adjusted for patient characteristics (age, sex, and OAB treatment status), mirabegron initiators had higher persistence rates. No significant differences were noted in unadjusted median time to end of persistence. However, end of treatment persistence by any cause was longer with mirabegron (median: 9.5 vs 6.7 months for antimuscarinics). HCPs stated that the most common reasons for nonpersistence were no symptomatic improvement and side effect aversion.. Treatment persistence was longer for mirabegron compared with antimuscarinic initiators after controlling for patient characteristics. End of treatment persistence by any cause was also longer with mirabegron.

Topics: Acetanilides; Adult; Humans; Muscarinic Antagonists; Prospective Studies; Registries; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To evaluate the efficacy and safety of mirabegron in children and adolescents (aged 3 to <18 years) with neurogenic detrusor overactivity (NDO) using clean intermittent catheterization.. In this open-label, multicenter, baseline-controlled, Phase III study (NCT02751931), participants received once-daily mirabegron at an adult dose equivalent of 25 mg. Dose was increased to 50 mg equivalent unless there were safety/tolerability concerns. The primary efficacy endpoint was change from baseline to Week 24 in maximum cystometric capacity (MCC). Secondary urodynamic assessments, Pediatric Incontinence Questionnaire (PIN-Q), Patient Global Impression of Severity (PGI-S), Clinician Global Impression of Change (CGI-C), and Acceptability questionnaires were included.. Overall, 86 participants (55 aged 3 to <12 years, 31 aged 12 to <18 years) received treatment; 68 were included in efficacy assessments. A statistically significant increase in MCC from baseline to Week 24 was observed (87.20 ml, 95% confidence interval: 66.07, 108.33; p < .001); this increase was apparent from Week 4. Significant increases in bladder compliance, bladder volume until first detrusor contraction, average volume per catheterization, maximum daytime catheterized volume and number of dry days per week. Significant decreases in detrusor pressure and number of leakage episodes per day were also observed. Significant improvement in PGI-S but not PIN-Q was observed. Most participants reported their condition had either much or very much improved using the CGI-C. Mirabegron was well tolerated in this population with a profile aligned with that in adults.. Mirabegron was effective and well-tolerated in the treatment of pediatric patients with NDO.

Topics: Acetanilides; Adolescent; Adult; Child; Humans; Thiazoles; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

Pre-post intervention.. 1. To test whether replacement of oral anticholinergic (AC) agents with mirabegron for neurogenic lower urinary tract dysfunction (NLUTD) yields improved cognitive function in older persons with spinal cord injury (SCI). 2. To test whether mirabegron is safe and as efficacious as AC.. USA.. Pilot study: Twenty older (>60 y/o) persons with SCI taking chronic (>6 months) AC medication for NLUTD were enrolled. All participants were first studied on AC at baseline then switched to mirabegron for 6 months. Primary outcomes were cognitive tests of (1) executive function (TEXAS, SDMT); (2) attention (SCWT); and (3) memory (SLUMS and WMS-IV Story A/B). Secondary outcomes assessed efficacy and safety including Neurogenic Bladder Symptom Score (NBSS), bladder diary, neurogenic bowel dysfunction (NBD) survey, heart rate (HR), electrocardiogram (EKG), and mean arterial pressure (MAP).. When switching from AC to mirabegron for NLUTD, older persons with SCI exhibited statistically significant improvements in immediate Story A recall (p = 0.01), delayed story A and B recall (p = 0.01, 0.004), and in TEXAS (p = 0.04). Three subscores within NBSS significantly improved (p = 0.001) and the frequency of incontinence decreased (p = 0.03) on mirabegron. NBD, HR, MAP, and EKGs were unchanged.. Older persons with SCI on AC for NLUTD demonstrated improved short-term and delayed memory (WMS-IV Story A/B) as well as executive function (TEXAS) when switched to mirabegron. Efficacy of mirabegron for NLUTD symptoms was superior to AC with no adverse effects on bowel or cardiovascular function.. Claude D. Pepper Older Americans Independence Center.

Topics: Acetanilides; Aged; Aged, 80 and over; Cholinergic Antagonists; Cognition; Humans; Pilot Projects; Spinal Cord Injuries; Thiazoles; Urinary Bladder, Overactive

During clinical trials, mirabegron, a β3-adrenoreceptor agonist, was associated with increased vital signs vs placebo in patients with overactive bladder.. The purpose of this study was to compare incidence rates of adverse cardiovascular (CV) outcomes following mirabegron or antimuscarinic use.. We conducted an observational post-marketing safety study utilising real-world data. The study population was identified within five sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (USA) and Humana (USA). Episodes of time when patients were new users of mirabegron or antimuscarinics (October 2012-December 2018) were sourced from prescriptions and matched on propensity scores. Occurrences of major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, CV mortality and all-cause mortality were identified. Outcome incidence rates and hazard ratios from Cox models were estimated.. Overall, 152,026 mirabegron and 152,026 antimuscarinic episodes were matched. The population consisted of 63.1% women and 72.6% were ≥ 65 years old. There were no appreciable differences in the incidence rates of MACE, AMI or stroke between users of mirabegron and antimuscarinics. Incidence rates of CV mortality (hazard ratio 0.83, 95% confidence interval 0.73-0.95) and all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76-0.84) were no higher with mirabegron vs antimuscarinics. Results restricted to episodes at high risk for CV events or stratified by age (< 65 years, ≥ 65 years) or prior overactive bladder medication use were consistent with overall findings.. This large, multinational study found no higher risk of MACE, AMI, stroke, CV mortality or all-cause mortality among users of mirabegron relative to users of antimuscarinics.. During clinical trials, mirabegron, which is a treatment for overactive bladder, was associated with small increases in heart rate and blood pressure. This study was conducted to compare the frequency of cardiac events following the use of mirabegron or antimuscarinics, a group of treatments also used to treat overactive bladder. We obtained the data for this study from four countries: Denmark, Sweden, the UK and the USA. We identified people who were new users of mirabegron or antimuscarinics from 2012 to 2018 using prescription or dispensing records. Occurrences of major cardiac events, heart attack, stroke, death due to cardiac events and death from any cause were evaluated. Overall, we identified 152,026 times when mirabegron or antimuscarinics were each used as new treatments. Most of the people in the study were women (63.1%) and at least 65 years old (72.6%). There were no notable differences between the treatment groups with regard to how often major cardiac events, heart attack or stroke occurred. Further, death due to cardiac events and death from any cause were no higher with mirabegron compared with antimuscarinics. We obtained similar results when the data were assessed for patients who were at high risk for cardiac events or split by age (less than 65 years or at least 65 years) or a history of overactive bladder medication use. In conclusion, this large study involving data from several countries found no higher risk of major cardiac events, heart attack, stroke or death among people prescribed mirabegron compared with antimuscarinics.

Topics: Acetanilides; Aged; Cardiovascular Diseases; Cohort Studies; Female; Heart Disease Risk Factors; Humans; Male; Muscarinic Antagonists; Risk Factors; Stroke; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

To evaluate the change of erectile function (EF) in sexually active male overactive bladder (OAB) patients treated with Mirabegron. Mirabegron, a selective β3 adrenoceptor agonist, approved for the treatment of OAB, has been reported to relax human and rat corpus cavernosum and might have beneficial effect on EF.. A total of 128 consecutive men with lower urinary tract symptoms attended urology outpatient clinic were evaluated for OAB and EF. Thirty-four sexually active OAB patients were prospectively enrolled in this study and received mirabegron 50 mg oral once a day. The evaluation of EF and OAB was based on a self-administered questionnaire containing International Index of Erectile Function (IIEF-5) and OAB symptom score (OABSS), respectively. Men with an OABSS urgency score of ≥2 and sum score of ≥3 were considered to have OAB. The therapeutic outcomes were assessed at baseline, 4, and 12 weeks.. Mirabegron usage was associated with a statistically significant improvement of OAB symptoms (OABSS 32.1% decrease) at 4-week follow-up and the therapeutic effects were maintained at 12-week follow-up. Mirabegron usage did not improve EF (IIEF-5 4.9% decrease at 4-week; p = 0.106, and 9.1% decrease at 12-week follow-up; p = 0.077). However, the IIEF-5 was significantly decreased in the higher baseline IIEF-5 (≥17) group (11.7% decrease; p = 0.044), noncoronary artery disease (13.2%; p = 0.007), or non-DM group (13.9% decrease; p = 0.021) at 12-week follow-up.. This preliminary study demonstrates that mirabegron treatment of men with OAB improved OAB symptoms, but has no beneficial effect on EF.

Topics: Acetanilides; Aged; Aged, 80 and over; Humans; Male; Middle Aged; Penile Erection; Prospective Studies; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Aged; Double-Blind Method; Humans; Thiazoles; Urinary Bladder, Overactive

To examine the effect of combining a nonselective muscarinic receptor antagonist, 5-hydroxymethyl tolterodine (an active metabolite of fesoterodine), with a β3 adrenoceptor agonist, mirabegron, in a rat model of pelvic congestion.. The rat pelvic congestion model used female Sprague-Dawley rats with their bilateral common iliac and uterine veins ligated. Expressions of M2 and M3 receptor subtypes in the urothelium and detrusor were detected by real-time polymerase chain reaction assays. The effects of both drugs were investigated on isolated bladder strips contracted by electrical field stimulation. in vivo single cystometry was used to assess the effects of 5-hydroxymethyl tolterodine and mirabegron independently or in combination on bladder capacity, micturition pressure, and threshold pressure.. Pelvic congestion rats showed decreased bladder capacity compared with controls, but micturition pressure and threshold pressure were unchanged. Pelvic congestion model rats also demonstrated an approximately two-fold increase in expression of both M2 and M3 receptor subtypes in the urothelium. Additive relaxant effects of 5-hydroxymethyl tolterodine and mirabegron were observed in vitro in the electrical field stimulation-induced contractions of bladder strips from pelvic congestion rats. In vivo, bladder capacity was increased significantly by a combination of 5-hydroxymethyl tolterodine and mirabegron, with the combined effect exceeding the sum of the effects of monotherapies. Micturition pressure and threshold pressure did not significantly differ between groups.. The combination of 5-hydroxymethyl tolterodine with mirabegron suggests the potential of synergistic effects in a rat pelvic congestion model.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Benzhydryl Compounds; Cresols; Disease Models, Animal; Drug Monitoring; Drug Therapy, Combination; Female; Muscarinic Antagonists; Rats; Rats, Sprague-Dawley; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Mirabegron, a selective β3-adrenoreceptor agonist, is a well-established alternative to antimuscarinics in adults with overactive bladder (OAB) symptoms and is under development for use in pediatric patients. Understanding drug pharmacokinetics (PK) in pediatric patients is needed to determine appropriate dosing. Conducting these studies is ethically complex, particularly as regulatory guidance requires that PK is assessed in pediatric patients with a therapeutic need for the drug. It is also vital to evaluate the safety/tolerability and palatability/acceptability of pediatric formulations.. The purpose of the study was to characterize the PK of mirabegron in pediatric patients with neurogenic detrusor overactivity or idiopathic OAB, to provide a basis for a weight-based dosing algorithm, and to evaluate the safety, tolerability, and palatability/acceptability of the formulations.. A preliminary population PK model constructed from adult data with allometric scaling was used to predict single weight-adjusted mirabegron doses. This was developed to achieve exposures in pediatric patients in two phase 1 studies that were consistent with steady state in adults following once-daily 25 mg ('low dose') and 50 mg ('high dose') dosing. In study 1, adolescents (12-<18 years) and children (5-<12 years) received a single tablet under fed or fasted conditions. In study 2, children (3-<12 years) received a single oral suspension dose under fed conditions. The PK data were used to assess the predictive value of the preliminary PK model and to update it to analyze mirabegron PK in pediatric patients. The safety/tolerability and palatability/acceptability of the formulations were evaluated.. Forty-three patients comprised six study cohorts: adolescents, low-dose tablets, fed (n = 7); children, low-dose tablets, fed (n = 7); adolescents, high-dose tablets, fed (n = 8); children, high-dose tablets, fed (n = 6); children, high-dose tablets, fasted (n = 6); and children, high-dose oral suspension, fed (n = 9). The population PK model-based doses for tablets and oral suspension achieved exposures that were typically consistent with steady state in adults. The final population PK model was used to describe the PK for mirabegron in pediatric patients (Table). Both formulations were well tolerated, and there were no reports of bad taste or swallowing difficulties for the tablets, although some found the oral suspension unpleasant.. The single, weight-adjusted pediatric mirabegron doses were successfully predicted by population PK modeling to achieve drug exposures comparable with steady state in adults. The finalized PK model used to characterize the pediatric PK of mirabegron will be utilized to develop a weight-based dosing algorithm. The single mirabegron doses were well tolerated.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Child; Child, Preschool; Cohort Studies; Female; Humans; Male; Thiazoles; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive

Topics: Acetanilides; Aged; Europe; Humans; Quality of Life; Thiazoles; Urinary Bladder, Overactive

Though the association between overactive bladder (OAB) and depression was noticed years ago, the pharmaceutical market does not offer one universal drug that would cure both conditions at the same time. The main goal of our present experiments was to determine whether a 14-day administration of solifenacin (0.03 mg/kg/day), mirabegron (1 mg/kg/day), or duloxetine (1 mg/kg/day) would reverse detrusor overactivity and depression-like signs in female Wistar rats subjected to corticosterone treatment. Surgical procedures, cystometric studies, biochemical analyses, and the forced swim test were performed according to published literature. After 14 days of exposure to corticosterone (20 mg/kg/day, subcutaneously), the tested animals presented symptoms of depression, detrusor overactivity, inflammation, and disturbances in neurotrophic factors. The obtained results demonstrated that solifenacin and mirabegron act mainly via peripheral pathways in OAB, whereas the central pathways are responsible for the effects of duloxetine. 72 h after discontinuation of duloxetine treatment, positive changes in the corticosterone-induced depression, detrusor overactivity, and inflammation were observed. Duloxetine seems to have a potential to become a new treatment option for patients with OAB co-existing with depression.

Topics: Acetanilides; Animals; Antidepressive Agents; Behavior, Animal; Corticosterone; Depression; Disease Models, Animal; Duloxetine Hydrochloride; Female; Locomotion; Rats; Rats, Wistar; Signal Transduction; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Today, monotherapy is the most common pharmacological treatment option for patients suffering from overactive bladder (OAB). Recent reports have indicated potential benefits of combination therapy, using a muscarinic antagonist and a β

Topics: Acetanilides; Animals; Cyclophosphamide; Cystitis; Disease Models, Animal; Drug Therapy, Combination; Male; Nitric Oxide; Random Allocation; Rats; Rats, Sprague-Dawley; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

The aims of this study were to evaluate the persistence, the adherence on treatment with mirabegron, the reasons for the interruption in patients with overactive bladder syndrome (OAB) and their satisfaction.. This was an Italian multicentre prospective study. Four tertiary urological centers were involved. We included women with no neurogenic OAB symptoms already in therapy with once-daily mirabegron 50 mg for 1 month. They were followed up at 1, 3 and 6 months post-treatment with uroflowmetry with voiding diary for 3 days and post-void residual measurement. They completed self-administered Overactive Bladder questionnaire short form (OABq), Morisky Medication Adherence Scale-4 short form (MMAS), Patient Global Impression-Improvement questionnaire. Patients were divided in OAB wet and OAB dry groups, and in treatment-naive and treatment-experienced groups.. Between January 2018 and July 2018, 80 patients with OAB were included. Fifteen (18.7%) patients continued the treatment for 6 months; 17.5% interrupted the therapy before 1 month: 30% within the third month, while, 33.7% after 1 month. The median time to discontinuation with mirabegron was 62.5 days. The mean adherence was 0.42 ± 0.33, median MMAS was 2 (0-4). The adherence was significantly greater in treatment-naïve (22.4%) than treatment-experienced (6.5%) patients, without statistically significant differences in the different OAB form. The cost is the main cause of interruption of therapy (50% of cases).There was an improvement of OABqSF score and PGI-I score.. In Italy, the cost compromises adherence and persistence of therapy with mirabegron despite the good functional outcomes.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Female; Humans; Italy; Medication Adherence; Middle Aged; Prospective Studies; Thiazoles; Urinary Bladder, Overactive

The BELIEVE study is a European, non-interventional study which includes patients with overactive bladder who were prescribed mirabegron as part of routine clinical practice. Data from the Spanish subpopulation has been obtained for the present study, aiming to analyze health-related quality-of-life (HRQoL) and treatment persistence of these patients.. Data from 11 Spanish hospitals of the BELIEVE study were analyzed. The primary endpoint was to evaluate change of HRQoL from baseline with overactive bladder questionnaire (OAB-q). Secondary endpoints included treatment persistence, HRQoL based on the EQ-5D-5L questionnaire and adverse events. Study follow-up was 12 months, with two visit windows at 2-4 months and 10-12 months.. 153 Spanish patients were enrolled in the study. In the Full Analysis Set (FAS), 63.1% were women, and the mean age was 66 years. Symptom bother and HRQoL improved from baseline to 2-4 months and 10-12 months. EQ-5D-5L questionnaire also showed an improved patients' HRQoL. Treatment persistence was high, as 49% of patients remained with mirabegron at 10-12 months. Adverse events were consistent with previous safety profile results of mirabegron, and no unexpected safety issues were observed.. Spanish patients treated with mirabegron in real clinical practice reported improvements in HRQoL, with a good tolerability and persistence to treatment.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Female; Humans; Male; Middle Aged; Quality of Life; Retrospective Studies; Self Report; Spain; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Humans; Male; Prostatic Hyperplasia; Tamsulosin; Thiazoles; Urinary Bladder, Overactive

To investigate the efficacy of mirabegron for lower urinary tract symptoms in patients with an indwelling ureteral stent after ureterorenoscopic lithotripsy. This was a prospective follow-up study of 76 patients with stent-related symptoms (SRSs). Patients with upper urinary calculi who were pre-stented for > 2 weeks before lithotripsy were examined for the presence of SRSs by tests including the International Prostate Symptom Score (IPSS), OAB Symptom Score (OABSS), and urinary bother and pain measured by a Visual Analogue Scale (VAS) before lithotripsy. Mirabegron (50 mg/day) was prescribed post-lithotripsy for 2 weeks. SRSs were assessed at the time of stent removal. The IPSS scores improved significantly from 16.2 to 14.3 (p<0.001) and the IPSS-QoL scores decreased significantly from 5.0 to 4.6 (p=0.012). The OABSS scores improved significantly from 7.7 to 6.8 (p=0.006), and the urinary urgency scores (OABSS-Q3) decreased significantly from 3.24 to 2.68 (p<0.001). The number of nocturia episodes decreased significantly from 2.5 to 2.2 (p=0.045). Urinary bother and pain assessed by the VAS declined from 4.2 and 3.1 to 3.8 (p=0.15) and 2.5 (p=0.075), respectively. Mirabegron significantly improved SRSs and the number of nocturia episodes due to a ureteral stent.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Female; Humans; Lithotripsy; Male; Middle Aged; Prospective Studies; Quality of Life; Stents; Thiazoles; Urinary Bladder, Overactive; Urinary Calculi

Intravesical prostatic protrusion (IPP) is associated with the degree of benign prostatic obstruction. We evaluated the effects of Mirabegron, a selective β3 adrenoceptor agonist, on overactive bladder (OAB) in male patients with different degrees of IPP.. About 185 male patients ≥40 years with lower urinary tract symptoms were recruited from a tertiary referral center. OAB was defined by the overactive bladder symptom score (OABSS) urgency score of ≥2 and sum score of ≥3. IPP was measured in the midsagittal section using transrectal ultrasound and patients were divided into IPP ≤5 mm and IPP >5 mm groups. Outcomes were assessed at the baseline, 4, and 12 weeks.. About 104 patients (56.2%) were diagnosed with OAB and received Mirabegron (50 mg) daily use. Both IPP groups (≤5 and >5 mm) had similar baseline OABSS and International Prostate Symptom Scores (IPSS). Four-week Mirabegron usage was associated with significant decreases in both symptom score measurements, OABSS: IPP ≤5 mm -27.4% and IPP >5 mm -19.7% (P = .419) and IPSS: -32% and -22.5% (P = .202), respectively. Urgency, urge incontinence, and nocturia sub-scores were decreased in both groups, -26.3% and -27.4% (P = .690), 53.3% and 46.2% (P = .916), and 20.8% and 15.4% (P = .958). Effects were maintained at 12 weeks. We found no significant improvement in the frequency sub-score in either group. One patient stopped medication because of intolerable hypertension. Most frequent adverse event was increased residual urine (≥50 mL higher than baseline), IPP ≤5 mm 9.2% and IPP >5 mm 5.1% (P = .707), but no case had acute urinary retention.. Mirabegron is an effective drug to treat male OAB regardless of IPP grade.

Topics: Acetanilides; Aged; Humans; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Brown adipose tissue (BAT), which produces energy and is known to play a role as a hibernating gland, is sometimes visualized on F-FDG PET in children or in slender young adults in a cold environment. Because BAT is activated by catecholamines, FDG uptake in BAT is also observed in patients with pheochromocytoma or paraganglioma. We present the case of an elderly woman with remarkable FDG uptake in BAT. Activation of BAT by a β3-adrenergic receptor agonist (mirabegron) prescribed for overactive bladder was suspected as the cause of the marked visualization of BAT in this patient.

Topics: Acetanilides; Adipose Tissue, Brown; Adrenal Gland Neoplasms; Adrenergic Agonists; Aged, 80 and over; Female; Fluorodeoxyglucose F18; Humans; Pheochromocytoma; Positron-Emission Tomography; Radiopharmaceuticals; Thiazoles; Urinary Bladder, Overactive

To evaluate whether the lower dropout rate of the treatment of overactive bladde r(OAB) with mirabegron could generate cost savings to the National Health System (NHS) and lead to quality-adjusted life years (QALYs) gains, compared to the most commonly prescribed antimuscarinics (AM) in Spain (tolterodine, fesoterodine, oxybutynin, solifenacin).. A probabilistic model (second order Monte Carlo simulation) in a hypothetical cohort of 1,000 patients with OAB and a time horizon of 1 year was carried out. Discontinuation and persistence rates for both mirabegron and AM were obtained from a Spanish observational study in 1798 patients. Unit costs (€ 2018) and utility loss associated with treatment discontinuation were obtained from Spanish public prices and literature, respectively.. Persistence rates in patients treated with mirabegron were twice as high compared to AM, leading to a QALY gain of 0.0151 ± 0.0007 per year. Treatment with mirabegron could generate savings of 80.74 ±4.61 € per patient per year compared to AM, assuming 100% probability of saving. The hypothetical substitution of AM treatment for mirabegron could potentially generate savings of 6.6 million euros (95% CI 3.9-10.1 million euros) to the NHS and 1,238 QALYs gains (CI95%731; 1,885 QALYs) within a period of 1 year.. The probabilistic model presented showed a greater persistence in patients treated with mirabegron compared to AM, leading to a positive impactin patients quality of life, as well cost savings to the NHS in Spain.. Evaluar si la menor tasa de abandonos del tratamiento de la vejiga hiperactiva (VH) con mirabegrón podría generar ahorros para el Sistema Nacional de Salud (SNS) y ganancia de años de vida ajustados por calidad (AVACs), en comparación con los fármacos antimuscarínicos (AM) (tolterodina, fesoterodina, oxibutinina, solifenacina).MÉTODOS: Modelo probabilístico (simulación de Monte Carlo de segundo orden) en una cohorte hipotética de 1.000 pacientes con VH y un horizonte temporal  de 1 año. Las tasas de abandono/persistencia del tratamiento con mirabegrón y AM se obtuvieron de un estudio observacional español en 1.798 pacientes. Los costes unitarios (€ 2018) y la pérdida de utilidades ligada al abandono del tratamiento se obtuvieron de precios públicos españoles y de la literatura, respectivamente.. En cada paciente tratado con mirabegrón se duplica la tasa de persistencia en comparación con los AM, ganándose anualmente 0,0151 ±0,0007 AVACs, frente a AM. Con mirabegrón se generaría un ahorro anual por paciente de 80,74 ± 4,61 € en comparación con los AM, con una probabilidad de ahorro del 100%. La sustitución hipotética de los AM por mirabegrón, generaría en el plazo de 1 año un ahorro para el SNS de 6,6 millones de euros (IC 95%3,9-10,1 millones de euros) y se ganarían 1.238 AVAC (IC95% 731; 1.885 AVAC).. El modelo probabilístico muestra una mayor persistencia en pacientes tratados con mirabegrón en comparación con los AM, generando un impacto positivo sobre la calidad de vida de los pacientes así como ahorros para el SNS.

Topics: Acetanilides; Humans; Models, Statistical; Muscarinic Antagonists; Quality of Life; Spain; Thiazoles; Urinary Bladder, Overactive

To compare the efficacies of mirabegron 50 mg addition after alpha-adrenoreceptor blocker in terms of reducing storage symptoms in patients with BPH.. Fifty-eight patients that had been taking alpha-adrenoreceptor blocker for more than 8 weeks, but had an OABSS of greater than 3 points, were initially enrolled. One group added any alpha-adrenoreceptor blocker with mirabegron 50 mg (n=39; the mirabegron group) and the other group received alpha-adrenoreceptor blocker only (n=19; the control group) for 8 weeks.. In the control group, mean total IPSS decreased from 15.7 to 13.1 (p=0.298) and in mirabegron group, mean total IPSS decreased from 19.4 to 16.5 (p=0.024). Mean storage symptom scores reduced in the control and mirabegron groups from 8.5 to 7.9 (p=0.584) and from 9.1 to 7.6 (p=0.015), respectively, and mean QoL scores from 3.7 to 3.1 (p=0.052) and 3.6 to 3.2 (p=0.027), respectively. Mean overall OABSS in the control and mirabegron groups reduced from 8.4 to 7.2 (p=0.173) and from 8.8 to 7.3, respectively (p=0.005); mean OABSS Q3 from 3.6 to 2.9 (p=0.073) and from 3.5 to 2.7 (p=0.002), respectively; and mean OABSS Q4 from 2.4 to 2.0 (p=0.306) and from 2.7 to 2.0 (p=0.016), respectively. The change of mean Qmax and PVR was insignificant in 2 groups.. IPSS total scores, storage symptom scores, QoL, overall OABSS, OABSS Q3 and Q4 were more improved significantly by alpha-adrenoreceptor blocker with mirabegron 50 mg in BPH patients with persistent overactive symptoms. Mirabegron 50 mg addition is considered to patients with persistent storage symptoms after alpha-adrenoreceptor blocker.

Topics: Acetanilides; Adrenergic alpha-Antagonists; Adrenergic beta-3 Receptor Agonists; Aged; Drug Therapy, Combination; Humans; Male; Middle Aged; Prospective Studies; Prostatic Hyperplasia; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

When patients with neurogenic bladder become refractory, there are different alternatives, such as the use of β3-adreceptor agonists. The aim of the present study is to evaluate efficacy and safety of Mirabegron as adjuvant treatment.. 37 patients under 18 years of age who underwent Mirabegron were retrospectively studied. The inclusion criteria were: cases with neurogenic bladder who were under clean intermittent catheterization (CIC) programs and refractory to oral oxybutynin (Group A) and/or onabotulinumtoxinA (Group B). Once refractory neurogenic bladder was confirmed by clinical and/or urodynamic studies, Mirabegron 25 mg/day was indicated and evaluation was performed in the third month without stopping therapy. Systolic/diastolic blood pressure and transaminases were monitored. Paired t test and Pearson's chi - squared test were used.. Maximum cystometric capacity increased significantly by 125 mL, from 322 to 446 ml (p < 0.0001). End-filling detrusor pressure decreased significantly by 12 cm H. In our study the treatment with Mirabegron improved significantly the clinical and urodynamic parameters. A significant increase in bladder capacity and a significant decrease in end-filling detrusor pressure were observed in both groups. The intensity of overactivity was attenuated. According to the records of the voiding diary, over 70% of the incontinent patients became dry after the administration of Mirabegron. We did not observe any adverse effects. The most important limitations of the present study are its retrospective design, the small size of the sample population and of each group, and the use of only one dose of Mirabegron.. Mirabegron as adjuvant treatment in children with refractory neurogenic bladder increased bladder capacity, reduced intravesical pressure and helped achieve continence in more than two thirds of the sample population. Mirabegron was safe and well tolerated by children.

Topics: Acetanilides; Adolescent; Child; Humans; Retrospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

Treatment patterns and costs were characterized among patients with overactive bladder (OAB) receiving later-line target therapies (combination mirabegron/antimuscarinic, sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], or onabotulinumtoxinA).. In a retrospective cohort study using 2013 to 2017 MarketScan databases, two partially overlapping cohorts of adults with OAB ("IPT cohort": patients with incident OAB pharmacotherapy use; "ITT cohort," incident target therapy) with continuous enrollment were identified; first use was index. Demographic characteristics, treatment patterns and costs over the 24-month follow-up period were summarized. Crude mean (standard deviation [SD]) OAB-specific (assessed by OAB diagnostic code or pharmaceutical dispensation record) costs were estimated according to target therapy.. The IPT cohort comprised 54 066 individuals (mean [SD] age 58.5 [15.0] years; 76% female), the ITT cohort, 1662 individuals (mean [SD] age 62.8 [14.9] years; 83% female). Seventeen percent of the IPT cohort were treated with subsequent line(s) of therapy after index therapy; among those, 73% received antimuscarinics, 23% mirabegron, and 1.4% a target therapy. For the ITT cohort, 32% were initially treated with SNS, 27% with onabotulinumtoxinA, 26% with combination mirabegron/antimuscarinic, and 15% with PTNS. Subsequently, one-third of this cohort received additional therapies. Mean (SD) costs were lowest among patients receiving index therapy PTNS ($6959 [$7533]) and highest for SNS ($29 702 [$26 802]).. Costs for SNS over 24 months are substantially higher than other treatments. A treatment patterns analysis indicates that oral therapies predominate; first-line combination therapy is common in the ITT cohort and uptake of oral therapy after procedural options is substantial.

Topics: Acetanilides; Adult; Aged; Botulinum Toxins, Type A; Combined Modality Therapy; Electric Stimulation Therapy; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Retrospective Studies; Thiazoles; Tibial Nerve; United States; Urinary Bladder, Overactive

We investigated the satisfaction and efficacy of mirabegron in patients with overactive bladder (OAB) symptoms who were unsatisfied with previous antimuscarinic treatment.. This was a 12-week, open-label study of adults with OAB who had been treated with antimuscarinics within 2 years of screening and expressed dissatisfaction over poor efficacy or adverse events of antimuscarinics. All enrolled patients have received mirabegron 50 mg once daily for 12 weeks. The primary outcome was the percentage of patients reporting treatment satisfaction questions (TSQ) at week 12 ("very satisfied" or "somewhat satisfied"). Patients completed voiding diaries, Overactive Bladder Questionnaire short form (OAB-q-SF), Overactive Bladder Symptom Score (OABSS), and the global response assessment (GRA) at baseline, Week 4, and Week 12. At 12-weeks, patients were assessed for willingness to continue treatment.. The response rate of treatment satisfaction at 12 weeks was 69.3% (275/397) (95% confidence interval 64.7-73.8). Significant improvements from baseline to weeks 4 and 12 were observed in the frequency, urgency due to urinary incontinence, and urgency episodes per 24 h (all p < .0001). Both OAB-q-SF and OABSS were significantly improved compared to baseline. At 4 and 12 weeks, 27.5% and 41.8% of patients, respectively, responded to the GRA as being moderately or markedly improved. At 12 weeks, 80.8% of patients were willing to continue mirabegron.. Mirabegron improved the rates of treatment satisfaction and symptoms in patients with OAB who were unsatisfied with prior antimuscarinic treatment.

Topics: Acetanilides; Aged; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Prospective Studies; Retreatment; Surveys and Questionnaires; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

To assess real-world treatment profiles, including the time to and reasons for discontinuation or drug switching, treatment reinitiation, and postdiscontinuation follow-up in patients receiving antimuscarinics or ß3-agonists for overactive bladder (OAB) through a retrospective chart review.. We retrospectively reviewed medical charts of 777 patients, aged ≥18 years, who underwent antimuscarinic or ß3-agonist therapy at our hospital. Data on patient's age, sex, chief complaint, and OAB symptom score at therapy initiation were collected. Treatment persistence was assessed with respect to the median time to discontinuation and the persistence rate at 12 months.. Older patients, male patients, and those with more severe urgency symptoms were more likely to show treatment persistence with OAB medications. Treatment persistence with mirabegron was significantly longer than that with antimuscarinics when administered as either the first- or second-line medication. Multivariate analyses showed that urgency severity and use of mirabegron were independently associated with better persistence (p = .026 and p = .018, respectively). Out of 583 patients who discontinued medication, 344 continued with the visit schedule, and the reinitiation rate of the OAB medication was 19% at a median follow-up of 24 months.. Although the persistence rates for OAB medications improved with the introduction of mirabegron, most patients still discontinued the medication therapy within 1 year. The treatment strategies for patients with mild symptoms and those who are resistant to medication can still be improved. Tailored individualized treatments that avoid excessive reliance on pharmacotherapy would be key to further improve treatment outcomes in OAB patients.

Topics: Acetanilides; Adult; Aged; Drug Substitution; Female; Humans; Male; Medication Adherence; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Retrospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Humans; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive

To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB).. Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis.. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3, 6 months, and 1 year, or at discontinuation (P < 0.001 at each time point). Kaplan-Meier treatment persistence rates were 84.8% at 3 months, 77.6% at 6 months, and 66.0% at 1 year. Treatment persistence rates were similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032).. Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Long-Term Care; Male; Middle Aged; Product Surveillance, Postmarketing; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

The incidence of overactive bladder (OAB) increases with age, especially in patients with central nervous system (CNS) disorders such as cerebrovascular accident (CVA) and Parkinson's disease (PD). Mirabegron is a novel medication for the treatment of OAB. The present study investigated the therapeutic effect of mirabegron on OAB patients with CNS diseases.. Patients with CVA, PD, dementia, and OAB symptoms were consecutively enrolled in the study group, and mirabegron 25 mg q.d. was prescribed. Clinical effects, evaluated using the Overactive Bladder Symptom Score (OABSS), Urinary Sensation Scale (USS), International Prostate Symptom Score (IPSS), and Patient Perception of Bladder Condition (PPBC), as well as urodynamic parameters and adverse events were assessed at baseline and 4 and 12 weeks after treatment.. In all, 44 patients (mean [± SD] age 77.7 ± 9.49 years) with OAB due to CVA (n = 27), PD (n = 6), and dementia (n = 11) were included in the present prospective study. Mirabegron resulted in significant improvements in symptom scores on the OABSS (P = .02), USS (P = .009), total IPSS (P = .002), Storage and Voiding domains of the IPSS (P = .001 and .017, respectively), and PPBC (P = .001). No significant changes were noted in post-void residual, maximum flow rate, and voided volume after treatment. Only 5 patients dropped out due to poor therapeutic efficacy and shifted to antimuscarinics. Three patients complained of adverse effects, including dizziness and dysuria. No patient complained of urine retention or constipation.. Mirabegron 25 mg once daily effectively decreased urgency symptoms in elderly OAB patients with CNS lesions after the 12-week treatment period. The adverse events were mild and only noted in a few cases.

Topics: Acetanilides; Aged; Central Nervous System Diseases; Dementia; Female; Humans; Male; Parkinson Disease; Stroke; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Mirabegron is widely considered as an effective and safe drug for patients with overactive bladder (OAB). However, there is no evidence regarding the efficacy of mirabegron in human T cell lymphotropic virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with OAB symptoms. The aim of the present study was to clarify the efficacy of mirabegron in HAM/TSP patients with OAB symptoms.. The present study evaluated the efficacy of mirabegron treatment (50 mg, once daily) in nineteen HAM/TSP patients with OAB symptoms by assessing subjective symptoms using the overactive bladder symptom score (OABSS) and International Prostate Symptom Score (IPSS) before and 12 weeks after administration. Voided volume (VV), maximum flow rate (Q. Mirabegron treatment improved OABSS in terms of night-time frequency, urgency, and total score (P < .001). In addition, on the IPSS, mirabegron therapy improved urgency, nocturia, storage symptoms (Questions 2, 4 and 7 on the IPSS), as well as the total score (P < .001). The quality of life (QoL) on the IPSS also improved after treatment (P < .001). However, there were no significant changes in objective symptoms, as measured by VV, Q. Mirabegron administration improved subjective symptoms in HAM/TSP patients with neurogenic OAB.

Topics: Acetanilides; Aged; Aged, 80 and over; Female; Human T-lymphotropic virus 1; Humans; Middle Aged; Paraparesis, Tropical Spastic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

We examined the efficacy and safety of mirabegron in elderly patients with urodynamic detrusor hyperactivity with impaired contractility (DHIC).. Patients diagnosed with DHIC received daily dose of mirabegron (25mg). Subjective symptom scores, uroflowmetry data, and adverse events (AEs) were recorded for all patients at baseline and after 1, 3, and 6 months treatment. Comparisons were made for each patient individually and between patients with detrusor overactivity (DO).. Of the 65 patients enrolled in the study, 25 had DHIC and 40 had DO (mean [± SD] age 79.3 ± 9.6 and 75.6 ± 10.7 years, respectively). At the 6-month follow-up, significant (P < .05) improvement was seen compared with baseline in both the DHIC and DO groups in terms of OAB symptom scores (4.72 ± 3.05 vs. 6.88 ± 4.06 and 4.50 ± 2.99 vs. 6.70 ± 3.60, respectively), urgency severity score (1.90 ± 2.00 vs. 3.35 ± 1.13 and 1.58 ± 1.93 vs. 3.00 ± 1.65, respectively), and global response assessment (1.80 ± 1.41 and 1.73 ± 1.34, respectively). In the DHIC group, post-void residual (PVR) volume decreased from 153 ± 52.7 mL at baseline to 85.8 ± 90.1 mL at 6th month (P < .05) and voiding efficiency improved from 40.0 ± 20.7% to 62.6 ± 28.3% (P < .05). Common AEs included dry mouth and dizziness, yet 16% of DHIC patients developed PVR >180 mL.. Mirabegron was an effective treatment option in elderly patients with urodynamic DO and DHIC in the present study. The AEs reported were mild and infrequent.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Female; Humans; Male; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics

To evaluate long-term antimuscarinic drug persistence and its associated characteristics in patients with overactive bladder (OAB) treated with antimuscarinic agents. We also assessed the efficacy and safety of switching from solifenacin to mirabegron in patients refractory to antimuscarinic therapy.. In this prospective, open-label, 48-month study, 416 patients (mean age, 70.6 ± 12.4 years) were enrolled. All patients completed the overactive bladder symptom score and urgency severity score questionnaires, along with initial and follow-up uroflowmetry. All patients received antimuscarinic solifenacin 5 mg daily. Mirabegron (25 mg daily) was suggested in patients that were refractory to antimuscarinic therapy or had intolerable side effects.. The mean solifenacin persistence was 6.6 ± 8.1 months (range, 0.5-48 months). Only 81 (19.5%) patients had drug persistence of ≥12 months. Male sex, age, cerebral vascular accident, maximum flow rate, and post-void residual were associated with solifenacin persistence in the univariate analysis. Age (odds ratio [OR], 0.14; 95% CI, 0.08-0.21) was the only independent predictor in the multivariate logistic regression. Of the 416 patients, 171 (60.8%) changed from solifenacin to mirabegron for due to the persistence of OAB symptoms. The switch resulted in a significantly longer period of actual OAB pharmacotherapy (9.3 ± 9.2 vs 13.3 ± 9.3 months, p < 0.001).. Long-term drug persistence of solifenacin was low during the 2-year follow-up. Age was an independent factor associated with longer drug persistence. Switching from solifenacin to mirabegron was an effective and safe alternative for OAB patients that were refractory to solifenacin treatment.

Topics: Acetanilides; Aged; Aged, 80 and over; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Muscarinic Antagonists; Prospective Studies; Severity of Illness Index; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

The aim of this study was to report the final 3-year results from a surveillance study evaluating the safety, efficacy, and persistence of mirabegron for treating overactive bladder (OAB) symptoms.. Patients who had started mirabegron for the treatment of urinary urgency, daytime frequency, and urgency urinary incontinence symptoms associated with OAB were followed for 3 years. Adverse drug reactions (ADRs), residual urine volume measurements, OAB symptoms, Overactive Bladder Symptom Scores (OABSS), and treatment discontinuations were evaluated prospectively. Persistence was estimated using the Kaplan-Meier method.. Of the 1138 patients included in the study (mean ±SD age: 71.9 ± 11.0 years; 574 [50.4%] women), 97 (8.52%) experienced 109 ADRs, with the incidence of ADRs decreasing over time (<1 year: 1.34%-2.37%; ≥1-<2 years: 0.45%-1.60%; ≥2-<3 years: 0.29%-1.10%; 3-monthly interval data). No significant increases in residual urine volume were observed. The investigators considered mirabegron to be an effective treatment for 842 of 1082 (77.8%) patients. Significant decreases in OABSS were reported throughout (P < 0.001), and 321 (65.1%) patients achieved a minimal clinically important change (MCIC) in OABSS. Most patients who achieved an MCIC within ≤1 year continued to maintain an MCIC throughout the study. Treatment persistence rates after 1, 2, and 3 years of mirabegron treatment were 65.8%, 52.9%, and 46.7%, respectively.. Over 3 years, mirabegron was well tolerated and no cumulative events or delayed ADRs were observed. Mirabegron was an effective treatment with early improvements in OABSS being maintained throughout the treatment period. High persistence was observed after the use of mirabegron.

Topics: Acetanilides; Aged; Female; Humans; Japan; Male; Middle Aged; Product Surveillance, Postmarketing; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Urological Agents

Topics: Acetanilides; Humans; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive

To assess the cost-effectiveness of onabotulinumtoxinA (onabotA), implantable sacral nerve stimulation devices, percutaneous tibial nerve stimulation, anticholinergic medications and mirabegron compared with best supportive care (BSC) for management of refractory overactive bladder (OAB).. A Markov model was developed to compare the cost-effectiveness of treatment options with BSC over a 10-year time horizon. Resource utilization, discontinuation rates and costs were derived from unpublished and published sources. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were reported.. Treatment with onabotA 100U produced the largest gain in QALYs (7.179) and lowest estimated incremental cost-effectiveness ratio ($32,680/QALY) of all assessed treatments compared with BSC.. Compared with BSC, onabotA 100U was the most cost-effective treatment option for patients with refractory OAB.

Topics: Acetanilides; Botulinum Toxins, Type A; Cholinergic Antagonists; Cost-Benefit Analysis; Electric Stimulation Therapy; Electrodes, Implanted; Health Care Costs; Humans; Middle Aged; Neuromuscular Agents; Thiazoles; Treatment Outcome; United States; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Humans; Japan; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive

This study investigated factors predicting the resumption of mirabegron following its discontinuation with successful treatment of overactive bladder (OAB).. In all, 374 OAB patients reporting an improvement in subjective symptoms after a minimum of 3 months treatment with mirabegron 25 mg, q.d., were screened. Those wanting to continue with the medication (n = 109) were excluded from the study. The remaining 265 patients discontinued mirabegron and their outcomes were evaluated at baseline (discontinuation) and 1, 3, 6, 9, and 12 months using the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), Urgency Severity Scale (USS), Patient's Perception of Bladder Condition (PPBC), and Global Response Assessment (GRA), as well as uroflowmetry and post-void residual (PVR).. After mirabegron discontinuation, 203 patients completed follow-up. The mean (±SD) duration from discontinuing medication to resumption of mirabegron was 2.25 ± 1.17 months (range 1-12 months). Compared with the 111 (54.7%) patients who did not resume mirabegron, the 92 (45.3%) patients who resumed mirabegron had a higher USS at time of discontinuation (1.18 ± 1.76 vs. 0.65 ± 1.33; P = 0.017). The USS was a strong predictor of mirabegron resumption (P = 0.02; odds ratio 1.315; 95% confidence interval 1.051-1.646).. Among OAB patients who were successfully treated with mirabegron for ≥3 months, nearly half requested resumption of mirabegron after discontinuation. A higher USS was found to predict retreatment after discontinuation of mirabegron in OAB patients.

Topics: Acetanilides; Aged; Female; Humans; Male; Quality of Life; Recurrence; Severity of Illness Index; Thiazoles; Urinary Bladder, Overactive; Urological Agents

To evaluate the effectiveness and persistence of mirabegron as a first-line treatment in patients with overactive bladder (OAB) in real-life practice.. We retrospectively analyzed patients with OAB who received mirabegron (50 mg) as a first-line treatment. According to treatment course, patients were divided into three groups, (a) mirabegron only (monotherapy group), (b) mirabegron and anticholinergics (add-on group), and (c) mirabegron replaced with another treatment (switch group). The patients' symptoms were documented with a voiding diary including an urgency scale and a patient perception of treatment benefit questionnaire (PPTB). Follow-up was at 4 weeks after initial treatment and then 2 months later, according to our routine protocol.. A total of 196 patients were included: 128 patients (65.3%) received monotherapy and 60 patients (30.6%) received add-on therapy. Eight patients discontinued mirabegron and switched to another treatment modality. The add-on group had more episodes of baseline urinary frequency, nocturia and urgency than the monotherapy group (P = 0.011, 0.001, and 0.006, respectively). In the monotherapy group, mean daily frequency, nocturia, urgency episodes, and urgency urinary incontinence were improved (P < 0.05) after mirabegron treatment. The persistence of mirabegron monotherapy was 68.0% at 3 months, 54.4% at 6 months, and 39.4% at 12 months. Treatment-naïve patients had better persistency than previously anticholinergics-treated patients.. Mirabegron is an effective first-line therapy for OAB, but has a persistence rate of 39.4% at 12 months. Patients with severe baseline OAB symptoms tended to require add-on therapy during follow-up.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Cholinergic Antagonists; Drug Substitution; Drug Therapy, Combination; Female; Humans; Lower Urinary Tract Symptoms; Male; Medication Adherence; Middle Aged; Retrospective Studies; Severity of Illness Index; Surveys and Questionnaires; Symptom Assessment; Thiazoles; Time Factors; Urinary Bladder, Overactive; Urological Agents

Overactive bladder (OAB) can frequently exert a negative effect on female sexual function. Mirabegron, a β3 receptor agonist, improves OAB symptoms, but there are very few information about its role on female sexual dysfunction (FSD). Aim of the study was to assess the impact of Mirabegron on FSD in women affected by OAB.. Fifty sexually active women suffering from idiopathic OAB were included in the study. Patients were assessed by means of a urogynecologic physical examination and were asked to complete the 3-day voiding diary, the International Consultation on Incontinence Questionnaire- Short Form (ICIQ-SF), the Female Sexual Function Index (FSFI) questionnaire and VAS, before and 12 weeks after treatment with Mirabegron. In addition, at the same time points, patients underwent uroflowmetry with the measurement of post- void residual volume (PVR).. At baseline all patients were affected by OAB symptoms, with 49/50 patients (98%) presenting with FSD. At 12- weeks follow- up, OAB symptoms improved significantly in all patients, with 59.5% of subjects achieving a complete urinary continence. FSFI Total Score significantly improved in 42/50 patients (84%) from 18.9 ± 4.3 to 21.8 ± 4.5 (p < 0.0001). Sixteen cases (32%) presented with no FSD. Also mean ± SD scores of ICIQ-SF and VAS significantly improved (from 17.1 ± 5 to 7.9 ± 4.8 and from 3.9 ± 1.2 to 6.9 ± 1.2 respectively, p < 0.000).. Mirabegron not only is able to control urinary symptoms in women with OAB, but also induces a significant improvement in their sexual life.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Female; Follow-Up Studies; Humans; Italy; Middle Aged; Prospective Studies; Sexual Behavior; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Thiazoles; Urinary Bladder, Overactive

To examine the efficacy and safety of non-ablative vaginal erbium:YAG laser (VEL) for the treatment of overactive bladder syndrome (OAB) compared with those of two other common pharmacotherapies, namely, anticholinergics and β3-adrenoceptor agonists.. Female subjects aged 60-69 years who presented with symptoms of OAB from 2015 to 2017 were assigned to three groups (n = 50) receiving treatment with an anticholinergic agent (4 mg fesoterodine), a β3-adrenoceptor agonist (25 mg mirabegron), or VEL (20 min/session of VEL performed thrice). The OAB symptom score (OABSS), Vaginal Health Index Scale (VHIS), and occurrence of adverse effects were examined prior to and at 1 year following treatment initiation.. The three groups showed significant improvement (p < 0.001) for all items of the OABSS questionnaire. Improved VHIS scores were observed only in the VEL group. Furthermore, after VEL treatment, a negative correlation was observed between questions 3 (urinary urgency) and 4 (urgency urinary incontinence) of the OABSS and VHIS. Regarding safety, no adverse events were observed in the VEL group. However, subjects in the other two groups complained of constipation, as indicated by the Constipation Assessment Scale scores, and mouth dryness. The therapeutic effects were inadequate for one and two subjects in the VEL and β3-adrenoceptor agonist groups, respectively.. VEL safely and effectively improved OABSS through a different mechanism than that involved in pharmacotherapy. We propose the use of VEL as a novel surgical treatment option in the field of urology.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Benzhydryl Compounds; Cholinergic Antagonists; Female; Humans; Lasers, Solid-State; Middle Aged; Prospective Studies; Syndrome; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urologic Surgical Procedures; Vagina

Topics: Acetanilides; Humans; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Humans; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive

Treatment of overactive bladder (OAB) with antimuscarinic agents has been shown to improve depression and/or anxiety symptoms.. The aim of this study was to evaluate the efficacy of mirabegron on OAB symptoms and its effects on depression and/or anxiety of treatment-naïve women with OAB.. Women treated with mirabegron were prospectively evaluated by the OAB symptom score and hospital anxiety and depression Scale before and at 4 and 8 weeks after treatment. Wilcoxon signed-rank and Spearman rank correlation coefficient were used for statistical analyses, and a p value of < 0.05 was considered as significant.. Of the 112 patients who were enrolled, 25.0% had been previously diagnosed as having clinical anxiety and 22.3% as having clinical depression. The OAB, anxiety, and depression symptom scores were significantly improved at both 4 and 8 weeks (p < 0.05). Anxiety, but not depression, symptoms were significantly correlated with OAB symptoms.. Improvement of OAB symptoms helps relieve anxiety, but not depression.

Topics: Acetanilides; Administration, Oral; Adult; Aged; Aged, 80 and over; Anxiety; Depression; Female; Humans; Middle Aged; Muscarinic Antagonists; Prospective Studies; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Mirabegron, a β. Participants (52 men, 118 women) with an initial mirabegron prescription were recruited nationwide from 79 pharmacies. Volunteers were interviewed at baseline and after 6 months. Subject and clinical characteristics, symptom severity, and quality of life (EQ-5D-5L) were assessed using a visual analogue scale.. Of 170 participants, 144 (84.7%) were reached after 6 months. The rate of persistent mirabegron use was 50.7%. Experiencing adverse effects (29.6%) was the most common reason for discontinuation of medication. A primary health care unit as a prescription site (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.03-4.9) was associated with increased risk for discontinuation. Mirabegron relieved symptoms in 45.2% and enhanced quality of life in 41.7% of the participants. Age <64 years was associated with better probability of symptom improvement (OR, 2.7; 95% CI, 1.1-6.8), whereas none of the other parameters assessed predicted change in quality of life.. In this Finnish population, 50.7% of the participants continued using mirabegron after 6 months. The prescription site seemed to be important for persistent use, which may be related to patient counseling. Younger patients were more likely to benefit from treatment with mirabegron.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Medication Adherence; Middle Aged; Quality of Life; Self Report; Thiazoles; Urinary Bladder, Overactive; Young Adult

To determine if findings at urodynamics prognosticate improvements in overactive bladder symptoms among women receiving mirabegron treatment.. Before treatment, women completed a urodynamic investigation, a micturition diary and the Urinary Distress Inventory (UDI) with the irritative subscale UDIOAB. After 6 months mirabegron treatment, patients were clinically evaluated and completed the UDI. Associations were tested using regression analyses and nonparametric statistics.. Testing urodynamic variables for association with treatment effects in multiple linear regression analysis showed that lower volumes at first sensation to void significantly correlated with greater improvement in the UDIOAB after 6 months mirabegron treatment (B = 0.026, 95% CI 0.002-0.049, p = 0.034). Improvements in UDIOAB showed no correlation with presence of nocturia (p = 0.65), previous use of anticholinergics (p = 1), menopausal status (p = 1), any detrusor overactivity during filling (p = 1), phasic detrusor contractions during filling (p = 1), or detrusor overactivity during inhibition (p = 1).. We found limited support for clinically relevant associations between findings at urodynamics and subsequent treatment outcomes for mirabegron in routine clinical practice. Our findings do not support the role of these investigations as predictors of outcomes in patients with overactive bladder symptoms.

Topics: Acetanilides; Adult; Aged; Diagnostic Techniques, Urological; Female; Humans; Middle Aged; Predictive Value of Tests; Prognosis; Thiazoles; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urination; Urodynamics; Urological Agents

Topics: Acetanilides; Humans; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Humans; Marketing; Thiazoles; Urinary Bladder, Overactive

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Antidepressive Agents; Benzilates; Benzofurans; Brazil; Clinical Decision-Making; Drug Therapy, Combination; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Pyrrolidines; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

5-Hydroxymethyl tolterodine (5-HMT; the active fesoterodine metabolite) is metabolized via the cytochrome P450 (CYP) 2D6 and CYP3A pathways. Mirabegron is a moderate CYP2D6 inhibitor and weak CYP3A inhibitor. Potential drug-drug interactions (DDIs) following coadministration of these 2 overactive bladder treatments were estimated using physiologically based pharmacokinetic models, developed and verified by comparing predicted and observed pharmacokinetic profiles from clinical studies. Models predicted and verified mirabegron and desipramine (CYP2D6 substrate) and 5-HMT and ketoconazole (strong CYP3A inhibitor) DDIs. Mirabegron model-predicted mean steady-state AUC and C

Topics: Acetanilides; Adult; Benzhydryl Compounds; Cresols; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Female; Humans; Ketoconazole; Male; Middle Aged; Rifampin; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Humans; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Aged, 80 and over; Benzhydryl Compounds; Benzofurans; Denmark; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Norway; Practice Patterns, Physicians'; Prospective Studies; Pyrrolidines; Registries; Solifenacin Succinate; Sweden; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

To describe quality of life outcomes in patients with overactive bladder aged ≥65 years receiving mirabegron, a β3-adrenoreceptor agonist (BELIEVE).. BELIEVE was a European, prospective, non-interventional, real-world study of 848 patients with overactive bladder prescribed mirabegron in clinical practice. Overactive bladder questionnaire subscales were prespecified primary end-points, analyzed in the full analysis set (patients completing the questionnaire at baseline and ≥1 follow-up visit) and per protocol set (patients still taking mirabegron at 10-12 months) using accepted standards for minimally important differences (10 points).. Nearly half of the patients in the full analysis set (380/796 [47.7%]) and per protocol set (224/452 [49.6%]) were aged ≥65 years. Similar proportions of patients aged ≥65 years (224/407; 55.0%) and <65 years (228/441; 51.7%) were taking mirabegron at 10-12 months. Mean symptom bother scores improved from baseline to month 10-12 in older patients (full analysis set 52.4 to 32.9; per protocol set 51.6 to 30.4) and younger patients (full analysis set 52.2 to 27.4; per protocol set 47.8 to 23.7). Proportions of older/younger patients with improvement in symptom bother were similar (full analysis set 52.1%/52.9%; per protocol set 70.1%/72.4%, respectively). Mean total quality of life scores improved in older patients (full analysis set 60.7-75.9; per protocol set 61.1-77.5) and younger patients (full analysis set 54.9 to 77.6; per protocol set 56.8 to 80.1). No unexpected safety issues were observed.. Patients aged ≥65 years receiving mirabegron in clinical practice reported clinically meaningful improvements in quality of life.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Adult; Age Factors; Aged; Aged, 80 and over; Europe; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Quality of Life; Surveys and Questionnaires; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Young Adult

Overactive bladder (OAB) is a syndrome with symptoms such as urinary frequency, urinary urgency and urge incontinence. The aim of this study is to assess the validity and reliability of the Turkish overactive bladder symptom score (OABSS) and to evaluate the results of mirabegron treatment with OABSS.. The study was carried out with 117 patients who applied to the urology outpatient clinic between June 2018-January 2019. OABSS Turkish validation was developed from the English version. Demographic data of the patients were recorded. The OABSS, overactive bladder questionnaire (OAB-v8) and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) were filled out by the patients. The patients were asked to fill in these questionnaires after 2 weeks. Patients receiving mirabegon treatment were evaluated with the same questionnaires and bladder diaries after 8 weeks.. A total of 117 OAB patients, including 82 OAB-wet and 35-OAB dry, were included in the study. The mean age of the patients was 46.79 ± 14.26 (18-78) years, and the mean duration of OAB complaint was 32.28 ± 32.21 months. The mean score of the OABSS is 9.9 ± 3.14. The results of the reliability assessment showed that the intraclass correlation coefficient of the total OABSS score was 0.71 (weighted coefficients of individual item points, 0.635-0.831), and the Cronbach α was 0.736. In the validity analysis, the OABSS total score was highly correlated with that belonging to other questionnaire forms (OAB-v8, ICIQ-SF and bladder diary). After the treatment with mirabegron, mean OABSS scores of the patients improved significantly from baseline to the 8th week (p < 0.001).. The Turkish version of the OABSS has been approved as a valid and reliable tool for evaluating OAB. Mirabegron used daily improved the symptoms of OAB in patients.

Topics: Acetanilides; Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Reproducibility of Results; Surveys and Questionnaires; Symptom Assessment; Thiazoles; Translations; Treatment Outcome; Turkey; Urinary Bladder, Overactive; Urological Agents; Young Adult

To understand differences in patient reported outcomes (PRO) between patients initiating mirabegron or an antimuscarinic using a validated PRO instrument, OAB-Satisfaction (OAB-S).. This prospective observational study used real-time prescription claims from Humana to identify Medicare patients initiating mirabegron or an antimuscarinic to participate in a series of three phone surveys over ninety days.. A total of 1897 mirabegron and 2444 randomly selected antimuscarinic initiators were identified; 174 mirabegron and 193 antimuscarinic initiators completed all three surveys. Among responders, mirabegron initiators were slightly older (76 vs 75 years, P = 0.032), included more males (32% vs 23%, P = 0.044), more likely to have prior OAB treatment (21% vs 13%, P = 0.048), and had greater medication burden (number of unique medications: 10.0 vs 8.7, P = 0.014). There were no between-group differences at any time or on any OAB-S scale. There were significant within-group differences at follow-up compared to baseline for OAB-S scales: "impact on daily living," with improvement over the 90-day survey period for both mirabegron (P = 0.008) and antimuscarinic (P < 0.001); "interruption of day-to-day life," with improvement for both mirabegron (P < 0.001) and antimuscarinic (P < 0.001); and improvement in "OAB control" for mirabegron (P < 0.001) and antimuscarinic (P < 0.001).. Mirabegron initiators tended to be older, had a greater number of unique medications and previously tried prescriptions to treat OAB; nonetheless, mirabegron, and antimuscarinic initiators reported similar trends in improvement in PROs over the first 90 days of treatment. Significant improvement in daily impact of OAB was observed after treatment initiation; however, no significant differences between groups were observed.

Topics: Acetanilides; Aged; Aged, 80 and over; Female; Humans; Male; Muscarinic Antagonists; Patient Reported Outcome Measures; Patient Satisfaction; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Observational studies can provide evidence about patient outcomes in routine clinical practice. This prospective, non-interventional study (BELIEVE) is the largest real-world European study to date to assess quality-of-life, treatment satisfaction, resource utilization, and persistence in patients with overactive bladder (OAB) who were prescribed mirabegron as part of routine clinical practice.. The primary objective was to evaluate change from baseline in quality-of-life based on overactive bladder questionnaire (OAB-q) sub-scales. Secondary objectives included evaluation of treatment persistence, patient satisfaction, healthcare resource utilization and adverse events (AEs). Follow-up was for 12 months with visit windows at 2-4 and 10-12 months. Median change from baseline in total OAB-q and its sub-scales (Health-related quality-of-life [HRQoL] and symptom bother scale) were assessed.. Overall, 862 patients were enrolled from eight European countries. In the Full Analysis Set (FAS), 73.7% were female, mean age was 61.2 years; 47.7% ≥65 years. At baseline, 41.3% had switched from other OAB treatments, 42.2% were treatment naïve, 10.1% were lapsed, and 6.4% were on combination treatment. Symptom bother and HRQoL total scores improved from baseline to 2-4 and 10-12 months. There was a notable improvement in dry rate, increasing from 34.9% at baseline to 43.7% at 10-12 months in the FAS, and a reduction in pad use. Persistence was high, with 53.8% of FAS patients remaining on mirabegron at 10-12 months. Overall, no unexpected safety issues were observed and AEs were consistent with the known safety profile of mirabegron.. Patients receiving mirabegron in a real-world setting reported meaningful improvements in QoL and health status, with a persistence rate of 53.8% at 12 months for the FAS. No unexpected safety issues were observed, and AEs were consistent with the known safety profile of mirabegron.

Topics: Acetanilides; Aged; Female; Humans; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Quality of Life; Surveys and Questionnaires; Thiazoles; Urinary Bladder, Overactive

The aim of this study was to compare the efficacy and tolerability of solifenacin and mirabegron in patients with overactive bladder (OAB) syndrome.. We carried out a retrospective analysis in 342 women affected by OAB syndrome; 168 were treated with solifenacin 5 mg/daily and 174 with mirabegron 50 mg/daily. A clinical evaluation, 3-day voiding diary, and urodynamic testing was performed. Patients completed the Overactive Bladder Questionnaire - Short Form, the King's Health Questionnaire, and the Patient Global Impression of Improvement questionnaire. The adverse effects were evaluated. The two groups were compared at baseline and at 12 weeks.. After 12 weeks, a significant reduction in the mean number/24 h of voids and urgent micturition episodes/24 h was observed in both groups. Detrusor overactivity decreased from 58.3% to 13.1% in the solifenacin group and from 58% to 11% in the mirabegron group. Twenty (12%) and 18 (10.7%) patients taking solifenacin reported constipation and dry mouth, respectively, versus four (2.3%) and five (2.9%) patients taking mirabegron, respectively, but there was no difference between the groups in the change in vital signs. The Overactive Bladder Questionnaire - Short Form and King's Health Questionnaire scores did not demonstrate significant differences and the abandonment rates in the solifenacin and mirabegron groups were 25.5% and 20%, respectively.. Solifenacin and mirabegron showed the same efficacy in the treatment of OAB but solifenacin had more adverse effects.

Topics: Acetanilides; Adult; Aged; Female; Humans; Middle Aged; Muscarinic Antagonists; Outcome Assessment, Health Care; Retrospective Studies; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive; Urological Agents

To compare the therapeutic efficacy and safety of mirabegron monotherapy in male patients with overactive bladder (OAB) with and without bladder outlet obstruction (BOO).. Male patients with OAB aged ≥20 years, with or without BOO, receiving mirabegron 25 mg monotherapy once daily, were prospectively enrolled. The treatment results were assessed using global response assessment, international prostate symptom score and subscores, overactive bladder symptom score, patient perception on intensity of urgency scale, patient perception of bladder condition, and quality of life index at 1 and 3 months after treatment.. Of the 289 enrolled patients (mean age, 71.2 years), 207 did not have BOO (71.6%) and 82 had BOO (28.4%). The baseline OAB symptoms were similar between patients with and without BOO. After mirabegron treatment, the satisfactory rate (global response assessment score ≧1) were similar between those without BOO (61.3%) and with BOO (57.1%). The improvement of quality of life index and patient perception of bladder condition was also found in both groups. However, only patients without BOO had significantly improved international prostate symptom score and subscores, overactive bladder symptom score, and patient perception on intensity of urgency scale. Although most adverse events (AEs) were mild, patients with BOO had significantly higher AEs rate (18.6%) than those without BOO (8.2%, P = .026).. Mirabegron monotherapy in male patients with OAB and BOO was safe. However, the storage symptoms improvement was less in patients with BOO and AEs rate was higher.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Humans; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Quality of Life; Severity of Illness Index; Thiazoles; Treatment Outcome; Urinary Bladder Neck Obstruction; Urinary Bladder, Overactive

To examine the long-term persistence rate with mirabegron in a real-world clinical setting.. We retrospectively collected the data of patients who were prescribed mirabegron. We investigated the persistence rate and the reason for the discontinuation. The analysis included patient's age, diagnosis, Overactive Bladder Symptom Score, prostatic volume, the prescription by specialists for lower urinary tract dysfunction, drug-naïve patients, replacement of antimuscarinics or add-on therapy to antimuscarinics.. A total of 556 patients were included. Among them, 401 patients (72%) had overactive bladder and the other 155 (28%) were categorized as having other storage symptoms. During the observation period, 170 patients (42%) with overactive bladder discontinued mirabegron. The reasons for discontinuation in patients with overactive bladder included unmet expectation of treatment (45 patients, 26%), any adverse events (38 patients, 22%) or symptom improvement (37 patients, 22%). The persistence or discontinuation was not related with age, Overactive Bladder Symptom Score, prostatic volume or the prescription by specialists, while older male patients tended to continue mirabegron. The 3-year persistence rates in female and male overactive bladder patients were 46% and 51%, respectively, and these were better than those in patients with storage symptoms without urgency. In female overactive bladder patients, the persistence rate with mirabegron used as add-on therapy to antimuscarinics was higher than that in the drug-naïve patients on the Kaplan-Meier curve.. The present study shows a relatively good long-term persistence rate with mirabegron in overactive bladder patients, notwithstanding the retrospective study in an academic hospital. The combined treatment with antimuscarinics could result in a good persistence rate with mirabegron.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Drug Therapy, Combination; Female; Humans; Japan; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Muscarinic Antagonists; Proportional Hazards Models; Retrospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Young Adult

To determine the impact of physicians' financial relationships with the pharmaceutical industry on prescribing marketed alpha-blockers and overactive bladder (OAB) medications. We also aim to examine if the number or total value of transactions is influential.. We linked the Open Payments Program database of industry payments to prescribers with Medicare Part D prescription data. We used binomial logistic regression to identify the association between receipt of industry payment and prescribing of marketed alpha-blockers (silodosin) and OAB medications (fesoterodine, solifenacin, and mirabegron). We also evaluated the impact of increasing total value and number of payments on prescribing of marketed drugs.. The receipt of industry payment was associated with increased odds of prescribing the marketed drug for all included drugs: silodosin (odds ratio [OR] 34.1), fesoterodine (OR 5.9), solifenacin (OR 2.7), and mirabegron (OR 6.8) (all P <.001). We also found that increasing value of total payment and increasing frequency of payments were both independently associated with increased odds of prescribing with a dose-response effect.. There is a consistent association between receipt of industry payment and prescribing marketed alpha-blockers and OAB medications. Both the total value and number of transactions were associated with prescribing.

Topics: Acetanilides; Adrenergic alpha-Antagonists; Benzhydryl Compounds; Databases as Topic; Drug Industry; Drug Prescriptions; Humans; Indoles; Medicare Part D; Practice Patterns, Physicians'; Solifenacin Succinate; Thiazoles; United States; Urinary Bladder, Overactive; Urological Agents; Urology

To examine early trends in the use of overactive bladder (OAB) agents across Canada, with a focus on initial uptake and reimbursement of two newer agents: fesoterodine, an anticholinergic, and mirabegron, a therapeutically novel beta-3 agonist.. We conducted a population-based cross-sectional study of outpatient prescriptions for long-acting oral OAB agents dispensed to individuals in Canada between May 2010 and April 2015 to examine the differences in the uptake of the newer agents and their reimbursement through cash, private, and public payers.. The national dispensing rate of OAB agents increased by 60% from May 2010 to April 2015 (from 924 to 1475 units per 10 000). We observed an increase in the dispensing rate of fesoterodine, solifenacin, and mirabegron, but a decrease in that of tolterodine and oxybutynin. Mirabegron was adopted rapidly after Health Canada approval, growing to a rate of 191 units per 10 000 by study completion, with its uptake being primarily funded through private payers (72.2%). Conversely, fesoterodine's uptake was minimal (8.3 units per 10 000) prior to its listing on public plans. This increased to 185 units per 10 000 by study completion, with the majority (65%) paid for by public insurers.. The differences in the uptake and reimbursement of two new OAB agents emphasize the impact of therapeutically novel agents on the prescription rates of older OAB agents with significant adverse effects. Further studies are needed to explain changes in the dispensing rates as more provinces list the newer drugs on their formulary.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Benzhydryl Compounds; Canada; Cholinergic Antagonists; Cross-Sectional Studies; Humans; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Humans; Muscarinic Antagonists; Network Meta-Analysis; Thiazoles; Urinary Bladder, Overactive

Pharmacotherapy of overactive bladder (OAB) typically involves treatment with an antimuscarinic or mirabegron, a β3-adrenoceptor agonist, but real-world evidence on their use, including treatment access, persistence, and switching, is limited. Here, we describe the design of a prospective, multicenter, non-interventional registry of patients beginning a new course of OAB pharmacological therapy in routine clinical practice.. Adults with an OAB diagnosis for at least 3 months who either initiated a new course of mirabegron or antimuscarinic, or who switched therapy were enrolled into PERSPECTIVE (a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder). The primary objective was to identify factors associated with improved OAB treatment effectiveness from a patient perspective. Secondary objectives were to compare persistence rates, reasons for discontinuation, and switching patterns between patients taking mirabegron or antimuscarinics. Healthcare centers and sites involving medical specialties who routinely participate in the care and treatment of patients with OAB (e.g., gynecology, urology, and primary care practices) were targeted for recruitment. Patient-reported outcomes (PROs), including quality of life, symptom bother, and treatment satisfaction from OAB-validated scales, were collected at baseline, months 1, 3, 6, and 12, and when patients switched or discontinued their current OAB medication.. PERSPECTIVE is the first real-world observational study in the United States and Canada on clinical and patient perspectives in OAB management. Recruitment was reflective of centers where patients are treated for OAB to maximize generalizability to the real-world population.. ClinicalTrials.gov, ID number NCT02386072 (date of registration March 6, 2015).

Topics: Acetanilides; Female; Follow-Up Studies; Humans; Male; Muscarinic Antagonists; Prospective Studies; Registries; Research Design; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Mirabegron is a relatively new drug to treat overactive bladder (OAB). The therapeutic doses are between 25 and 100 mg in clinical trials. We aimed to evaluate the efficacy and persistence of low-dose mirabegron (25 mg) in patients with OAB in daily urological practice.. The study was a retrospective consecutive cohort of 177 OAB patients (101 male and 76 female) treated with 25 mg of mirabegron mg since January 2016 to November 2016. The therapeutic outcomes were assessed at baseline, 4, 12, and 24 weeks.. Mirabegron usage was associated with a statistically significant decrease in Overactive Bladder Symptom Score, Urgency Severity Score, urge urinary incontinence, International Prostate Symptom Score (both storage and voiding symptom) at 4-week follow-up, and the therapeutic effects were further improved at 12- and 24-week follow-up. Among them, 118 patients (66.7%) and 84 patients (47.5%) were maintained on mirabegron therapy for more than 3 and 6 months, respectively. However, 29 patients (16%) had poor response with drug discontinuation within 3 months and 8 patients (4.5%) stopped medication due to adverse effects. The overall side effect was 10.2%, and the most common side effect was elevated blood pressure (2.8%) and increased post-void residual (2.8%). Between male and female patients, there was no statistical difference of symptom improvement and drug persistence rate.. Low-dose mirabegron (25 mg) improves clinical outcomes in two-thirds of OAB patients with good safety profile and high persistence in daily urological practice. The therapeutic effect is similar between the genders.

Topics: Acetanilides; Adult; Aged; Female; Humans; Hypertension; Male; Middle Aged; Patient Dropouts; Quality of Life; Retrospective Studies; Severity of Illness Index; Surveys and Questionnaires; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Benzhydryl Compounds; Canada; Humans; Thiazoles; Urinary Bladder, Overactive

The present study assessed the therapeutic efficacy and safety of mirabegron 25 mg in older patients aged ≥80 years with overactive bladder and multiple comorbidities.. Patients with overactive bladder were prospectively treated with 25 mg of mirabegron once daily. The patients were divided into a younger group (aged 40-60 years) and an older group (aged ≥80 years), and their underlying comorbidities were recorded. The primary efficacy end-point was the change in symptom score from baseline to the third month. Safety assessments included adverse events and post-void residual urine volume.. A total of 217 patients (younger, n = 62; older, n = 155) were included. The older patients had more comorbidities than the younger patients. Statistically significant improvements in the Quality of Life index and Patient Perception of Bladder Condition were noted in the younger patients from 1 month after treatment, whereas the International Prostate Symptom Score-Voiding subscore, International Prostate Symptom Score-Total, Quality of Life index, post-void residual urine volume and Patient Perception of Bladder Condition were all significantly decreased in the older patients after 3 months of treatment. The mean changes in the International Prostate Symptom Score-Voiding subscore, maximal flow rate, post-void residual urine volume, nocturia and Urgency Severity Score were significantly different between the two groups. The younger patients experienced more minor adverse events than the older patients (41.94% vs 24.62%) during treatment. Nevertheless, the adverse event rate was acceptably low in both groups.. Mirabegron 25 mg once daily is a safe and effective treatment for older patients with overactive bladder. Geriatr Gerontol Int 2018; 18: 1330-1333.

Topics: Acetanilides; Age Factors; Aged; Aged, 80 and over; Cohort Studies; Comorbidity; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multimorbidity; Patient Safety; Prospective Studies; Quality of Life; Risk Assessment; Sex Factors; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Humans; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive

The objective of the study was immunohistochemical evaluation of distribution of various NO synthase fractions in the structural elements of the bladder wall under stress urinary incontinence and its overactivity prior and post Mirabegron, Spasmex, Quercetin therapies and their combinations with Testosterone and Estradiol. Using the immunohistochemical method, we studied the expression of the main fractions of NO synthase in experimental models of hyperactive bladder (OAB) and stress urinary incontinence (SUI). We found that OAB and SUI were characterized by emergence of expression of the inducible fraction (iNOS) predominantly in the interstitial cells of the muscular layer of the bladder and reduced expression of endothelial (eNOS) and neuronal (nNOs) NO synthase fractions. In contrast to Spasmex, Mirabegron and Quercetin in combination with Testosterone and Estradiol contributed to stabilization of eNOS and nNOs expression already at early observation phases, and reduced the level of iNOS expression with its further disappearance in the later observation period.

Topics: Acetanilides; Animals; Benzilates; Drug Therapy, Combination; Estradiol; Female; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nortropanes; Quercetin; Rats; Testosterone; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence, Stress

This study aimed to assess the outcomes of mirabegron for the treatment of overactive bladder (OAB) symptoms in patients with Parkinson disease (PD).. A retrospective study was conducted including patients with PD who received mirabegron 50 mg once daily for OAB symptoms between 2012 and 2017. The primary endpoint was clinical success defined as any improvement in overactive bladder symptoms self-assessed by the patients 6 weeks after mirabegron initiation. Secondary endpoints included number of pads per day, number of nocturia episodes and adverse events.. Fifty patients (mean 74 years old) were included. Before being treated with mirabegron, 56% had failed prior anticholinergic therapy. After 6 weeks of mirabegron 50 mg, five patients (11.4%) had a complete resolution of their OAB symptoms; 25 patients (50%) reported improvement, 23 (46%) reported no change and 2(4%) reported worsening of their OAB symptoms. The number of pads per day decreased from 1.5 to 0.9 (p = 0.01) and so did the number of nocturia episodes (from 3 to 2.6/night; p = 0.02). Only 2 adverse events were reported during mirabegron treatment (4%): one dizziness and one diaphoresis, that disappeared after mirabegron discontinuation. After a median follow-up of 19 months, 23 patients (46%) persisted on mirabegron. Persistence rates were 51.5%, 44.6% and 36.4% at 1, 2 and 3 years respectively.. Mirabegron has an excellent safety profile and appears to be an effective treatment for overactive bladder symptoms in patients with PD. Further prospective randomized trials are needed to properly assess mirabegron in PD patients.

Topics: Acetanilides; Aged; Cohort Studies; Female; Humans; Male; Middle Aged; Parkinson Disease; Retrospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Succinate, an intermediate metabolite of the Krebs cycle, can alter the metabolomics response to certain drugs and controls an array of molecular responses in the urothelium through activation of its receptor, G-protein coupled receptor 91 (GPR91). Mirabegron, a

Topics: Acetanilides; Animals; Cyclic AMP; Female; Metabolic Syndrome; Muscle Relaxation; Muscle, Smooth; Myocytes, Smooth Muscle; Nitric Oxide; Nitric Oxide Synthase Type II; Rats; Receptors, Adrenergic, beta-3; Signal Transduction; Succinic Acid; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive; Urothelium

To assess the cost-effectiveness of mirabegron 50 mg relative to tolterodine extended release 4 mg for the treatment of overactive bladder if used as the first-line treatment in Japan.. A Markov model was developed to simulate the cost-effectiveness of the mirabegron first-line treatment (and tolterodine second-line) versus tolterodine first-line treatment (and mirabegron second-line) taken for 5 years from the randomized European-Australian study (SCORPIO trial) and single technology appraisal assessment report by the National Institute for Health and Care Excellence. The incremental cost-effectiveness ratio was calculated with utility value by quality-adjusted life year with cost using the medical fee and the drug price tariff in 2016. For the study of transition of treatment status, our analytical model was established. The transition probabilities of severity states were calculated based on the probabilities for the mean numbers of incontinence episodes/day and micturition episodes/day in mirabegron-treated and tolterodine-treated patients in the single technology appraisal assessment report.. The 5-year expected effect per patient was 3.860 quality-adjusted life years for first-line mirabegron and 3.839 quality-adjusted life years for first-line tolterodine. The 5-year expected cost per patient was ¥526 191 for first-line mirabegron, and ¥472 390 for first-line tolterodine. The incremental cost-effectiveness ratio was ¥2 565 927/quality-adjusted life year. This value was below the willingness-to-pay threshold of ¥5 million/quality-adjusted life year. In more severe states, the incremental cost-effectiveness ratio exceeded ¥5 million.. First-line mirabegron appears to be more cost-effective than first-line tolterodine. In patients with severe symptoms, first-line mirabegron is not economically preferable.

Topics: Acetanilides; Cost-Benefit Analysis; Delayed-Action Preparations; Drug Costs; Humans; Japan; Markov Chains; Muscarinic Antagonists; Quality of Life; Severity of Illness Index; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Persistence on-treatment with antimuscarinics in patients with overactive bladder (OAB) is reported to be sub-optimal. This retrospective, longitudinal, observational cohort study assessed treatment persistence with β. Adults who received mirabegron or an antimuscarinic in routine clinical practice (1 June-31 October 2014), were identified from anonymised prescription data within the Spanish Cegedim Electronic Medical Records database. The primary endpoint, treatment persistence (time to treatment discontinuation [TTD] and the proportion of patients remaining on-treatment after 12 months), was unadjusted for potential confounders. Multivariate Cox regression models of persistence, adjusted for baseline characteristics, were used to compare differences in treatment groups. Adjusted subgroup analyses (target OAB drug, age, treatment status and sex) and sensitivity analyses (extending the time used to define treatment discontinuation from 30 days [base-case] to 45, 60 or 90 days without prescription renewal) were also performed.. Overall, 1798 patients received mirabegron (N = 1169) or an antimuscarinic (N = 629); the mean age was 66.42 years. Median TTD was longer for mirabegron versus antimuscarinics (90 vs 56 days) and a higher proportion of patients who received mirabegron were persistent after 12 months (20.2% vs 10.2%); multivariate analyses indicated significantly greater persistence with mirabegron versus antimuscarinics (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.37-1.70; p < 0.001). Significant differences were also observed in subgroup analyses of mirabegron versus individual antimuscarinics (median TTD: 90 vs [range] 28-60 days; HR range: 1.21-2.17; p ≤ 0.013) and in all other subgroups assessed (p < 0.001). Sensitivity analysis showed that the median TTD for mirabegron increased by up to 31 days, and was significantly longer versus antimuscarinics across all adjusted periods (HR range: 1.43-1.53; all p < 0.001).. Patients with OAB in Spain who received mirabegron experienced longer persistence on-treatment than those who received antimuscarinics and the proportion of patients persistent on-treatment at 12 months with mirabegron was two-times higher versus antimuscarinics. These data may provide strategic insights for clinicians and policy makers involved in the management of OAB.

Topics: Acetanilides; Aged; Aged, 80 and over; Female; Humans; Linear Models; Longitudinal Studies; Male; Medication Adherence; Middle Aged; Muscarinic Antagonists; Proportional Hazards Models; Retrospective Studies; Spain; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Overactive bladder (OAB) is defined as urgency, with or without urge incontinence, usually with frequency and nocturia. Antimuscarinic drugs are often prescribed as a standard care; however, the treatment discontinuation due to the adverse events including dry mouth and constipation has been an issue. Taking these situations into account, we considered that a novel OAB drug having a different mechanism from antimuscarinics fills the unmet medical need. It has been known that, during bladder filling, activation of sympathetic nerves results in bladder smooth muscle relaxation via the β-adrenergic receptor (AR) stimulation. In 1999, three Japanese groups independently provided evidence for the existence of β

Topics: Acetanilides; Animals; Humans; Rats; Thiazoles; Urinary Bladder, Overactive; Urological Agents

For managing overactive bladder (OAB), mirabegron, a β3 adrenergic receptor agonist, is typically used as second-line pharmacotherapy after antimuscarinics. Therefore, patients initiating treatment with mirabegron and antimuscarinics may differ, potentially impacting associated clinical outcomes. When using observational data to evaluate real-world safety and effectiveness of OAB treatments, residual bias due to unmeasured confounding and/or confounding by indication are important considerations. Falsification analysis, in which clinically irrelevant endpoints are tested as a reference, can be used to assess residual bias. The objective in this study was to compare baseline cardiovascular risk among OAB patients by treatment, and assess the presence of residual bias via falsification analysis of OAB patients treated with mirabegron or antimuscarinics, to determine whether clinically relevant comparisons across groups would be feasible. Linked electronic health record and claims data (Optum/Humedica) for OAB patients in the United States from 2011-2015 were available, with index defined as first date of OAB treatment during this period. Unadjusted characteristics were compared across groups at index and propensity-matching conducted. Falsification endpoints (hepatitis C, shingles, community-acquired pneumonia) were compared between groups using odds ratios (ORs) and 95% confidence intervals (CI). The study identified 10,311 antimuscarinic- and 408 mirabegron-treated patients. Mirabegron patients were predominantly older males, with more comorbidities. The analytic sample included 1,188 antimuscarinic patients propensity-matched to 396 mirabegron patients; after matching, no significant baseline differences remained. Estimates of falsification ORs were 0.7 (CI:0.3-1.7) for shingles, 1.5 (CI:0.3-8.2) for hepatitis C, 0.8 (CI:0.4-1.8) and 0.9 (CI:0.6-1.4) for pneumonia. While propensity matching successfully balanced observed covariates, wide CIs prevented definitive conclusions regarding residual bias. Accordingly, further observational comparisons by treatment group were not pursued. In real-world analysis, bias-detection methods could not confirm that differences in cardiovascular risk in patients receiving mirabegron versus antimuscarinics were fully adjusted for, precluding clinically relevant comparisons across treatment groups.

Topics: Acetanilides; Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Comorbidity; Data Interpretation, Statistical; Databases, Factual; Electronic Health Records; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Propensity Score; Retrospective Studies; Risk Factors; Thiazoles; United States; Urinary Bladder, Overactive; Urological Agents; Young Adult

Topics: Acetanilides; Female; Humans; Prospective Studies; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Humans; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive

Overactive bladder is a composite of lower urinary tract storage symptoms. Pharmacological treatment is widely employed despite markedly modest efficacy data, adverse effects, and costs for the health system.. To determine the 12-month efficacy of an intervention delivered by GPs on mirabegron revision and, if appropriate, discontinuation of treatment.. Multicentre, quasi-experimental study in Barcelona (Catalonia), Spain.. Two groups composed of 17 intervention and 34 control practices were formed. The follow-up period was 12 months, from 1 January to 31 December 2017. A structured intervention was designed consisting of initiatives with GPs and urology/gynaecology specialists. The primary outcome was mirabegron use at 12 months.. Of the 1932 patients, a significant discontinuation in treatment was observed at 12 months' follow-up in the intervention group (IG) (. The structured intervention showed optimisation in the use of mirabegron. When considering discontinuation it is necessary to provide clear data on the benefits and/or risks for patients and their caregivers, as such information is a precondition for shared decision making.

Topics: Acetanilides; Aged; Aged, 80 and over; Controlled Before-After Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Primary Health Care; Spain; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To provide real-world data on Japanese patients with overactive bladder (OAB) initiating treatment with the β. Full medical histories, including prior/concomitant drug use, were collected before initiating mirabegron treatment. After 12 weeks mirabegron, physicians assessed ADR incidence and treatment effectiveness. Residual urine volume was assessed and patients completed the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score-Quality of Life (I-PSS QoL) surveys at Baseline and 12 weeks. Data were collected between April 2012 and July 2014.. Of 9795 OAB patients (46.8% male; 80.8% ≥65 years), 71.7% had coexisting disease [notably benign prostatic hyperplasia (BPH, 32.4%), hypertension (31.9%), and diabetes mellitus (9.4%)] and 53.4% reported concomitant drug use (27.8% α. In the clinical setting, mirabegron is well tolerated, with no unanticipated ADRs, and is an effective treatment for Japanese patients with OAB.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Diabetes Complications; Drug Administration Schedule; Female; Humans; Hypertension; Male; Middle Aged; Product Surveillance, Postmarketing; Prostatic Hyperplasia; Quality of Life; Severity of Illness Index; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Retention; Urological Agents

The objective of the present study was to evaluate comparative efficacy and tolerability of antimuscarinics and mirabegron as primary and salvage therapy in patients with overactive bladder (OAB).. Patients ≥50 years with OAB symptoms were enrolled. Patients were initially treated with antimuscrinics or mirabegron for 8 weeks. When patients were refractory or intolerant to an initial treatment, drugs were switched to the other. The initial and second-line efficacy was assessed at baseline, 4 and 8 weeks after the treatment having the following parameters of the International Prostatic Symptom Score (IPSS), quality of life (QOL) index, Overactive Bladder Symptom Score (OABSS) and post-void residual (PVR) urine volume. Dry mouth and constipation were evaluated using dry mouth scale and constipation assessment scale, respectively.. A total of 117 patients were enrolled. As an initial treatment, 60 patients were given antimuscarinics and 57 patients received mirabegron. Similar initial treatment efficacy was observed between the two drugs in the whole patients. However, mirabegron was more efficacious to men with OAB unresponsive to prior α1-blocker. Dry mouth and constipation were less burdensome in patients treated with mirabegron. Such differences in efficacy and tolerability were associated with significantly greater persistence of mirabegron. As a second-line setting, both drugs appear to be equally effective at least to relieve urgency symptoms remaining after an initial therapy.. The present study suggests that mirabegron seems to have priority as an initial therapy with a distinct efficacy/tolerability balance. Mirabegron also represents a reasonable alternative to antimuscarinics for patients who had insufficient efficacy and poor tolerability.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Analysis of Variance; Drug Substitution; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Prospective Studies; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Catheterization; Cohort Studies; Female; Humans; Incidence; Male; Middle Aged; Muscarinic Antagonists; Prostatic Diseases; Randomized Controlled Trials as Topic; Residual Volume; Risk; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Retention; Urodynamics; Urological Agents

Adherence and persistence rates of anticholinergic (ACH) therapies have been well described. To date, few studies describe these metrics for mirabegron in patients with overactive bladder.. This retrospective analysis of MarketScan. The mean age of mirabegron users (n = 4037) was 67 years and 43% were ACH naïve while the mean age of ACH users was 62 years (n = 67,943). Over the 12-month follow-up period, 44% of patients treated with mirabegron and 31% of patients treated with ACH were adherent to their indexed medications. Treatment failure was 81% for mirabegron and 88% for ACH. Most mirabegron treatment failures were because of treatment discontinuation (67%) versus switching to ACH therapy (14%). The ACH discontinuation rate was 84% and treatment switching rate was 4%. The mean (standard deviation) time to treatment failure was 143 (130) days for mirabegron and 69 (69) days for ACH. Adherence and persistence patterns were similar in the sensitivity analysis using a ≥ 45-day supply gap threshold.. This real-world study demonstrated low adherence and persistence to mirabegron similar to ACH therapies.

Topics: Acetanilides; Adult; Aged; Cholinergic Antagonists; Databases, Factual; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Patient Compliance; Retrospective Studies; Thiazoles; Treatment Refusal; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Thiazoles; Urinary Bladder, Overactive

We aimed to assess the patient-reported outcome (PRO) and efficacy of add-on low-dose antimuscarinic therapy in over-active bladder (OAB) patients with suboptimal response to 4-week treatment with beta 3 agonist monotherapy (mirabegron, 50 mg).. We enrolled OAB patients with 4-week mirabegron (50 mg) treatment if the patients' symptoms improved, but not to a satisfactory extent (patient perception of bladder condition [PPBC] ≥4). Enrolled patients had 8-week low-dose antimuscarinics add-on therapy (propiverine HCl, 10 mg). Patients recorded 3-day voiding diary at screening, enrollment (after 4 weeks of mirabegron monotherapy) and after 8 weeks of add-on therapy. We assessed the change of PRO (PPBC) as a primary end point and the efficacy of add-on therapy (change of frequency, urgency, urinary urgency incontinence [UUI] based on voiding diary) as a secondary end point.. Thirty patients (mean age, 62.3±12.8 years; mean symptom duration, 16.0±12.3 months) were finally enrolled in the study. The mean PPBC value was 4.3±0.4 after mirabegron monotherapy, and decreased to 3.2±1.0 after 8-week add-on therapy. The mean urinary frequency decreased from 10.1±3.1 to 8.8±3, the mean number of urgency episodes decreased from 3.6±1.6 to 1.8±1.2 and the number of urgency incontinence episodes decreased from 0.7±1.0 to 0.2±0.5 after add-on therapy. No patients had event of acute urinary retention and three patients complained of mild dry mouth after add-on therapy.. Add-on therapy of low-dose antimuscarinics exhibits good efficacy and safety in patients with suboptimal response after 4-week of mirabegron (50 mg) monotherapy.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

The American Urological Association (AUA) stands at the forefront of technology development and urological education for urologists and urological healthcare professionals worldwide. The 112th annual meeting brought together a wide range of researchers in the field of urology to access knowledge, up-to-date clinical guidelines and advances in research. The meeting consisted of plenary and moderated poster, podium and video sessions highlighting the latest research and advances in urological medicine. This report highlights some of the presentations on therapeutic developments for a range of urological conditions.

Topics: Acetanilides; Administration, Intranasal; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Clinical Trials, Phase III as Topic; Deamino Arginine Vasopressin; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Humans; Hydrogels; Mitomycin; Multicenter Studies as Topic; Nocturia; Randomized Controlled Trials as Topic; Solifenacin Succinate; Thiazoles; United States; Urinary Bladder Neoplasms; Urinary Bladder, Overactive; Urology

To compare healthcare costs and resource utilization in patients with overactive bladder (OAB) in the US who switch from mirabegron to onabotulinumtoxinA (onabotA) with those who persist on mirabegron.. A retrospective observational claims analysis of the OptumHealth Administrative Claims database conducted between April 1, 2012 and September 30, 2015 used medical and pharmacy claims to identify patients with at least one OAB diagnosis who switched from mirabegron to onabotA (onabotA group) or persisted on mirabegron for at least 180 days (mirabegron persisters). Propensity score weighting was used to balance baseline characteristics that were associated with increased healthcare expenditures across treatment groups. Multivariate analyses assessed the impact of switching and persistence on all-cause and OAB-related healthcare costs and resource utilization in the year following each patient's index date.. In total, 449 patients were included in this study: 54 patients were included in the onabotA group, and 395 patients were included in the mirabegron persister group. Compared with the mirabegron persister patients, the onabotA patients observed significantly higher OAB-related total costs ($5,504 vs $1,772, p < .001), OAB-related medical costs ($5,033 vs $351, p < .001), sacral neuromodulation costs ($865 vs $60, p = .017), and outpatient costs ($17,385 vs $9,035, p = .009), and more OAB-related medical visits (6.0 vs 1.9, p < .001). OnabotA patients had lower OAB-related prescription costs ($470 vs $1,421, p < .001) and fewer OAB-related pharmacy claims (1.6 vs 5.0, p <.001). There were no significant differences in all-cause total medical or prescription costs.. This study was a retrospective analysis using claims data that only included patients with commercial health coverage or Medicare supplemental coverage. Accuracy of the diagnosis codes and the generalizability of the results to other OAB populations are limited. The study was not designed to determine the impact of OAB treatments on the economic outcomes examined.. OAB patients who persisted on mirabegron treatment for at least 180 days had lower OAB-related healthcare costs and resource utilization compared with those who switched to onabotA.

Topics: Acetanilides; Adult; Aged; Botulinum Toxins, Type A; Female; Health Expenditures; Health Resources; Humans; Insurance Claim Review; Longitudinal Studies; Male; Middle Aged; Retrospective Studies; Thiazoles; United States; Urinary Bladder, Overactive; Urological Agents

To evaluate persistence and adherence to mirabegron and antimuscarinics in Japan using data from two administrative databases.. The present retrospective study evaluated insurance claims for employees and dependents aged ≤75 years, and pharmacy claims for outpatients. From October 2012 to September 2014, new users of mirabegron or five individual antimuscarinics indicated for overactive bladder in Japan (fesoterodine, imidafenacin, propiverine, solifenacin and tolterodine) were identified and followed for 1 year. Persistence with mirabegron and antimuscarinics were evaluated using Kaplan-Meier methods. Any associations between baseline characteristics (age, sex and previous medication use) and persistence were explored. Adherence was assessed using the medication possession ratio.. In total, 3970 and 16 648 patients were included from the insurance and pharmacy claims databases, respectively. Mirabegron treatment was associated with longer median persistence compared with antimuscarinics (insurance claims: 44 [95% confidence intervals 37-56] vs 21 [14-28] to 30 [30-33] days, pharmacy claims: 105 [96-113] vs 62 [56-77] to 84 [77-86] days). The results were consistent when patients were stratified by age, sex and previous medication. Persistence rate at 1 year was higher for mirabegron (insurance claims: 14.0% [11.5-16.8%] vs 5.4% [4.1-7.0%] to 9.1% [5.3-14.2%], pharmacy claims: 25.9% [24.6-27.3%] vs 16.3% [14.0-18.6%] to 21.3% [20.2-22.4%]). Compared with each antimuscarinic, a higher proportion of mirabegron-treated patients had medication possession ratios ≥0.8.. This large nationwide Japanese study shows that persistence and adherence are greater with mirabegron compared with five antimuscarinics.

Topics: Acetanilides; Adult; Female; Humans; Japan; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Muscarinic Antagonists; Retrospective Studies; Thiazoles; Urinary Bladder, Overactive

Persistence with antimuscarinic (AM) drugs prescribed for overactive bladder (OAB) is poor. This study aimed to compare persistence and adherence with the beta-3-adrenoceptor agonist mirabegron (MIR) vs AMs over 12 months.. This retrospective cohort analysis included patients aged ≥18 years who were prescribed MIR, or any AM. A 12-month look-back was used to assess inclusion eligibility. The primary end-point was persistence, defined as time to first discontinuation of index drug, during 1 year follow-up. The secondary end-point was adherence, estimated by medication possession ratio (MPR).. Inclusion criteria were met by 6189 patients. Those prescribed AMs were mostly treatment-naïve (range 72.9%-95.3%) vs 54.4% of MIR patients. There was greater persistence with MIR vs AM. The median number of days on therapy with MIR was 101, vs 27-56 for AMs. Patients receiving AMs were significantly more likely to discontinue than those receiving MIR (hazard ratio [HR] range 1.24-2.05, P < .01 for each AM vs MIR. In treatment-naïve patients, HRs ranged from 1.25 (solifenacin, P = .012) to 2.07 (oxybutynin IR, P < .001). In treatment-experienced patients, they ranged from 1.10 (fesoterodine, P = NS) to 2.12 (oxybutynin IR, P < .001). Adherence was greater with MIR (mean MPR 48.4%) than with AMs (range 27.6%-40.4%, P < .001). Treatment-experienced patients were significantly less likely to discontinue treatment (HR 0.87, P = .006).. MIR was associated with a significantly longer time to discontinuation, greater persistence and better adherence than AMs. However, there was a steep decline in persistence with all drugs after 1 month. This is unlikely to be wholly explained by anticholinergic adverse events, as it was also seen with MIR. The lower proportion of MIR patients who were treatment-naive reflects current prescribing guidelines whereby MIR is prescribed after an initial generic AM trial. The study was limited by the small number of MIR patients. Study identifier: ISN 178-MA-3059.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Cohort Studies; Female; Humans; Male; Medication Adherence; Middle Aged; Muscarinic Antagonists; Retrospective Studies; Thiazoles; United Kingdom; Urinary Bladder, Overactive

This technical update addendum reviews success rates and comparative evidence of the anticholinergic fesoterodine, as well as mechanism of action, safety profile, success rates, and comparative evidence of the β3 agonist mirabegron in the treatment of non-neurogenic overactive bladder syndrome (OAB). This adds to OAB pharmacotherapy recommendations initially published in 2012.. Residents and other trainees, primary care practitioners, gynaecologists, urologists, urogynaecologists, and other health care providers who assess, counsel, and treat women with OAB.. Adult women with symptomatic OAB.. This addition relates to fesoterodine, mirabegron, and anticholinergic-β3 agonist combination pharmacotherapy.. The outcomes of interest are clinical efficacy of fesoterodine compared with no treatment or other OAB therapies; mechanism of action and safety profile of mirabegron, clinical efficacy of mirabegron compared to no treatment or other OAB therapies; clinical efficacy of anticholinergic-β3 agonist combination pharmacotherapy for OAB.. PubMed, Medline, and the Cochrane Database were searched using the key words "fesoterodine" and "mirabegron." Results were restricted to English or French and human clinical and pharmacological research. Animal research and clinical studies including only male participants were excluded. Articles were included until the end of December 2016. Grey literature was not searched. Clinical practice guidelines, guidelines of specialty societies, and systematic reviews were included. RCTs and observational studies were included when evidence for the outcome of interest or in the target population was not available from systematic reviews. New studies not yet included in systematic reviews were also included. References of included articles were also searched to ensure comprehensive inclusion of relevant literature.. The content and recommendations were drafted and agreed upon by the principal author, as well as members of the Urogynaecology Committee. The Board of the SOGC approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework. The Summary of Findings is available upon request.. It is expected that this technical update will benefit patients with OAB by providing physicians and other interested health care providers with additional options for and knowledge of safe and effective OAB pharmacotherapy. The benefits clearly outweigh the potential harms or costs of implementation of this technical update, although there are no direct harms or costs identified. UPDATES: "Evidence will be reviewed 5 years after publication to decide whether all or part of the document should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations.". Not applicable.

Topics: Acetanilides; Benzhydryl Compounds; Drug Therapy, Combination; Female; Humans; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Benzhydryl Compounds; Contraindications, Drug; Drug Therapy, Combination; Female; Humans; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Cholinergic Antagonists; Drug Therapy, Combination; Follow-Up Studies; Humans; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics

Multiple sclerosis (MS) is the commonest progressive neurological disease affecting young people. With advancing disease, management of neurogenic detrusor overactivity (NDO) based on antimuscarinics may prove inadequate and if based on botulinum toxin, may necessitate clean intermittent self-catheterization. The aim of the study was to evaluate the effectiveness of combined mirabegron and desmopressin administration in the treatment of NDO in patients with MS.. Sixty patients diagnosed with MS and NDO were evaluated. All had received treatment with solifenacin 10 mg/daily for 3 months and were displeased with the results. Patients were divided in four groups. In Group A (n = 15) patients continued receiving solifenacin 10 mg/daily; in Group B (n = 15) patients received mirabegron 50 mg/daily; in Group C (n = 15) patients received desmopressin 120 mcg/daily and in Group D (n = 15) patients received mirabegron 50 mg/daily and desmopressin 120 mcg/daily. All patients were assessed with a 3 day bladder diary at the beginning and at the end of the treatment.. All patients in Groups A, B and C did not demonstrate statistically significant changes at the end of the treatment period in their 3 day bladder diary and in the presence of urinary infections. In Group D, a statistically significant improvement was noted in the mean change from baseline to end of treatment in micturition episodes (3.5 +/- 0.4 micturition/24h), in urgency episodes (2.3 +/- 0.2) and mean number of urinary incontinence (1.0 +/- 0.2 episodes/24h).. Treatment with mirabegron and desmopressin revealed both effectiveness and safety in patients with NDO and MS.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Antidiuretic Agents; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Muscarinic Antagonists; Retreatment; Solifenacin Succinate; Thiazoles; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence; Urination

To evaluate persistence rates of patients receiving mirabegron therapy for overactive bladder (OAB) within our institution over a 6 month period, identify determinants of early discontinuation of therapy, and assess overall patient satisfaction with treatment.. Hospital prescription data were analyzed in order to identify all patients who had been prescribed mirabegron in our institution. Case notes were retrospectively reviewed to obtain demographic data, previous treatments for OAB, reasons for discontinuation of previous treatments, and duration of treatment with mirabegron. Overall satisfaction with treatment was assessed using the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q).. One hundred and ninety-seven patients were prescribed mirabegron. Of these, 81% previously discontinued anticholinergic therapy, 14% had previously received intravesical botulinum toxin A therapy, and 19% were prescribed mirabegron first-line. At 3 months 69% persisted with treatment which fell to 48% by 6 months. The commonest reason for discontinuation was lack of efficacy, followed by adverse effects. Overall 32% of patients preferred mirabegron over previous treatments and only 39% were satisfied with mirabegron therapy.. Persistence rates with mirabegron in this group of patients for OAB are satisfactory. The commonest reasons for discontinuation are unmet treatment expectations and adverse effects. We had very few treatment-naïve patients and so further studies are required to assess mirabegron persistence rates with longer-term follow up, as first-line treatment and in different groups of OAB severity. Neurourol. Neurourol. Urodynam. 36:404-408, 2017. © 2015 Wiley Periodicals, Inc.

Topics: Acetanilides; Adolescent; Adult; Aged; Aged, 80 and over; Child; Female; Humans; Male; Middle Aged; Patient Satisfaction; Retrospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents; Young Adult

Mirabeg ron is a selective β3-adrenoceptor agonist approved for the treatment of overactive bladder (OAB). Four phase 1 studies were conducted in healthy subjects to evaluate the potential for pharmacokinetic interactions between mirabegron and metformin, warfarin, digoxin, or a combination oral contraceptive (COC).. Thirty-two male subjects received metformin (500 mg twice daily) or mirabegron (160 mg once daily) alone, in combination or with placebo. Twenty-four male and female subjects received single doses of warfarin (25 mg) alone and in combination with mirabegron (100 mg once daily). Twenty-five male and female subjects were administered digoxin (0.25 mg) alone and in combination with mirabegron (100 mg once daily). Thirty female subjects received low-dose COC containing ethinylestradiol (EE)/levonorgestrel (LNG) (30/150 µg once daily) in combination with mirabegron (100 mg once daily) or placebo. Pharmacokinetic parameters were determined by non-compartmental methods. Absence of a Pharmacokinetic interaction was concluded if the 90 % confidence intervals (CI) of geometric least-squares means ratio of area under the curve (AUC) and maximum concentration (C. Mirabegron increased digoxin AUC and C. No dose adjustment of either drug is required when mirabegron is administered concomitantly with metformin, warfarin or COC. Patients receiving mirabegron with digoxin may require additional monitoring of digoxin concentrations with dose adjustments where necessary, due to its narrow therapeutic index.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Area Under Curve; Contraceptives, Oral, Combined; Digoxin; Double-Blind Method; Drug Interactions; Female; Healthy Volunteers; Humans; Male; Metformin; Thiazoles; Urinary Bladder, Overactive; Warfarin

This study determined if combined treatment with the muscarinic receptor (MR) antagonist solifenacin and the β. Thirty-two female 10-week-old SHRs were fed an 8% NaCl-supplemented diet for 4 weeks. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then intravenously administered vehicle, 0.1 mg/kg solifenacin alone, 0.1 mg/kg mirabegron alone, or the combination of 0.1 mg/kg mirabegron and 0.1 mg/kg solifenacin (n = 8 each group). Five minutes later, the treated rats were exposed to low temperature (LT, 4 ± 2°C) for 40 min. Finally, the rats were returned to RT. After the cystometric investigations, the β. Just after transfer from RT to LT, vehicle-, solifenacin-, and mirabegron-treated SHRs exhibited detrusor overactivity that significantly decreased voiding interval and bladder capacity. However, treatment with the combination of solifenacin and mirabegron partially inhibited the cold stress-induced detrusor overactivity patterns. The decreases of voiding interval and bladder capacity in the combination-treated rats were significantly inhibited compared to other groups. Within the urinary bladders, there were no differences between expression levels of M. This study suggested that the combination of solifenacin and mirabegron act synergistically to inhibit the cold stress-induced detrusor overactivity in SHRs. Neurourol. Urodynam. 36:1026-1033, 2017. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Cold Temperature; Disease Models, Animal; Drug Therapy, Combination; Female; Muscarinic Antagonists; Rats; Rats, Inbred SHR; Solifenacin Succinate; Stress, Physiological; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive; Urological Agents

To evaluate the effects of the beta-3 adrenoceptor agonist, mirabegron in a mouse model of detrusor overactivity induced by obesity.. C57BL/6 male mice were fed with standard chow or high-fat diet for 12 weeks. Lean and obese mice were treated orally with mirabegron (10 mg/kg/day) from the last 2 weeks of diet. Cystometric evaluations, functional assays, protein expression for phosphodiesterase type 4 (PDE4), and cyclic adenosine monophosphate (cAMP) measurement were carried out.. In obese mice the body weight, epididymal fat mass, fasting glucose, and low-density lipoprotein (LDL) levels were higher (P < 0.001) than in the lean mice. A reduction of 34% and 54% and an increase of 35% in the epididimal fat, LDL, and HDL levels (P < 0.05), respectively, were observed in the obese group treated with mirabegron, whereas no changes were seen in the lipid profile from lean mice. Obese group showed irregular micturition pattern, characterized by significant increases in frequency and non-void contractions. Carbachol, potassium chloride, and electrical-field stimulation induced detrusor smooth muscle (DSM) contractions, which were greater in bladders from obese mice than from lean mice. Two-week treatment with mirabegron restored all the contractile response alterations in the DSM. Basal intracellular levels of cAMP were reduced (68%), whereas PDE4 protein expression was increased (54%) in bladder from obese mice. Mirabegron restored the cAMP levels in obese bladder, without changing the PDE4 expression.. Mirabegron was able to completely restore the urinary alterations seen in the bladder from obese mice.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Body Weight; Carbachol; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 4; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle Contraction; Muscle, Smooth; Obesity; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive; Urination

Mirabegron (β3 adrenoreceptor agonist) is a new molecule with a mechanism of action distinct from antimuscarinics. Combination therapy with solifenacin was recently studied in an adult population. We evaluated the efficacy and safety of mirabegron as add-on therapy to treat urinary incontinence in children with idiopathic overactive bladder refractory/intolerant to antimuscarinics.. A prospective off-label study using add-on regimens of mirabegron was conducted in pediatric patients presenting with no symptom improvement while undergoing intensive behavioral and medical therapies and/or significant side effects while undergoing antimuscarinic dose escalation. Our primary outcome was better reported efficacy than with the use of prior antimuscarinic monotherapy. Secondary end points were tolerability, safety and satisfaction. Efficacy and tolerability were assessed based on voiding diaries, post-void residuals, urine cultures, electrocardiograms and vital signs. Families were questioned regarding continence, side effects and compliance. Wilcoxon signed-rank test was used for statistical analysis.. A total of 35 patients were recruited at a median age of 10.3 years and were administered add-on mirabegron for a median of 16.4 months. Median bladder capacity improved from 50% to 74% expected bladder capacity (p <0.001). Continence improved in all patients, with 12 being completely dry. Post-void residual was increased in 2 patients and 1 urinary tract infection was reported. Seven patients reported mild or moderate side effects, with 2 withdrawals because of side effects (1 patient) and post-void residual (1).. Add-on mirabegron appears to be a safe alternative for children with refractory overactive bladder. Dual therapy is well tolerated and adjusted dose regimen appears safe in this first pediatric study.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Male; Muscarinic Antagonists; Prospective Studies; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive

No previous studies have investigated the efficacy of mirabegron 50 mg as the first-line therapy in OAB patients. Hence, the primary objective of this study was to evaluate the efficacy of mirabegron in treatment-naive patients in comparison with those who had discontinued antimuscarinic therapy because of insufficient efficacy.. All consecutive women who had pure OAB symptoms (including urgency with or without urgency incontinence and frequency) for at least 3 months were considered for this study. Women were divided into two groups: women without any previous pharmacological treatment for OAB (group 1) and women with a previous history of failed antimuscarinics therapy (group 2).. At 3-month follow-up, the objective results on the basis of the frequency-volume chart showed a significant improvement in both groups. Furthermore, a significant reduction in the Overactive Bladder Questionnaire Short Form (OABq-SF) score and in the Indevus Urgency Severity Scale (IUSS) questionnaire were reported in both groups. However, the improvement in objective and subjective outcomes was superior in group 1 to that in group 2.. Mirabegron is efficacious in improving OAB symptoms in both naïve patients and those who discontinued primary antimuscarinic therapy; however, its efficacy is superior when prescribed as first-line therapy.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Humans; Middle Aged; Prospective Studies; Thiazoles; Urinary Bladder, Overactive

The impact of formulary management strategies on utilization and expenditures in overactive bladder (OAB) treatment has not been extensively investigated. In 2013, step therapy (ST) policies for 2 branded OAB treatments, mirabegron and fesoterodine, were removed from Humana Medicare Advantage Prescription Drug (MAPD) plans and Medicare prescription drug plans (PDP), allowing for an examination of the effect of ST policies on OAB medication use patterns and costs.. To assess the impact of removal of formulary restriction policies for mirabegron and fesoterodine on medication utilization patterns and costs associated with OAB treatment in Medicare patients.. A retrospective cross-sectional study design was utilized. Subjects included individuals enrolled in Humana MAPD plans or PDPs, aged ≥ 65 years, with ≥ 1 prescription for an OAB medication in 2013. Patient demographic characteristics, OAB medication utilization, and pharmacy cost trends in 2013 were described. OAB medication use was calculated as the number of 30-day-supply equivalent medication claims and reported as a percentage of the total number of 30-day-supply equivalent claims across all OAB products. OAB medication expenditures were calculated as a percentage of the sum of pharmacy costs for OAB medications and reported separately for each month and drug during 2013. Temporal trends of OAB medication utilization and expenditures in 2013 were calculated using ordinary least squares regression.. Of 194,511 patients, trends in utilization of OAB medications indicated that on average, there was a statistically significant monthly increase in utilization of mirabegron (regression coefficient [B] = 274; P < 0.001; 95% CI: 218, 330), fesoterodine (B = 167; P < 0.001; 95% CI = 129, 205), oxybutynin extended release (ER; B = 357; P = 0.011; 95% CI = 99, 614), and trospium ER (B = 33; P = 0.001; 95% CI = 17, 50) and statistically significant decreases in utilization of solifenacin (B = -202; P = 0.048; 95% CI = -402, -2), tolterodine ER (B = -287; P = 0.002; 95% CI = -437, -137), darifenacin (B = -94; P < 0.001; 95% CI = -128, -61), and trospium immediate release (IR; B = -22; P = 0.001; 95% CI = -32, -12). Total OAB medication expenditures significantly increased an average of 0.12% for each month during the course of 2013 (B = 0.12; P = 0.026; 95% CI = 0.017, -0.223). While monthly oxybutynin IR utilization did not change significantly throughout 2013 (B = 228; P = 0.169; 95% CI = -114, -570), it demonstrated the largest average monthly expenditure increase (B = 0.082; P < 0.001; 95% CI = 0.056, 0.108). When removing oxybutynin IR costs from the total OAB medication costs, the trend in total OAB medication average monthly expenditures was not significant (B = 0.038; P = 0.365; 95% CI = -0.051, -0.126). An over 4-fold per-unit-cost increase for oxybutynin IR was noted.. Utilization of 2 branded OAB products increased in the months after ST removal with minimal cost impact. One of the possible reasons total OAB expenditures increased may have been due to the increased cost of the largest-volume generic product, oxybutynin IR.. This research was funded by Astellas Pharma Global Development and was conducted as part of the Astellas-Humana Research Collaboration. Ng, Kristy, Schermer, and Bradt are employees of Astellas. Astellas manufactures mirabegron (Myrbetriq) and solifenacin (VESIcare). Abbass, Caplan, Collins, and Suehs are employees of Comprehensive Health Insights, a subsidiary of Humana, which received funding from Astellas for this study. Suehs owns stock in Humana. Chan is an employee of Humana Pharmacy Solutions. Portions of this study were presented as a poster at Academy of Managed Care Pharmacy Nexus 2015; October 26-29, 2015; Orlando, Florida. Study concept and design were contributed by Ng, Chan, Suehs, and Abbass, along with Collins. Abbass took the lead in data collection, along with Collins and with assistance from Caplan, Chan, and Suehs. Data interpretation was provided by Kristy and Bradt, along with Abbass, Caplan, Ng, Suehs, Collins, and Chan. The manuscript was written primarily by Caplan, along with Schermer, Suehs, and Abbass, and revised by Caplan, Schermer, and Ng, along with the other authors.

Topics: Acetanilides; Aged; Benzhydryl Compounds; Cross-Sectional Studies; Drug Utilization; Female; Health Care Costs; Health Expenditures; Humans; Male; Managed Care Programs; Medicare; Muscarinic Antagonists; Retrospective Studies; Thiazoles; United States; Urinary Bladder, Overactive; Urological Agents

The objective of this project was to evaluate treatment persistence in patients being treated for overactive bladder syndrome (OAB) with mirabegron, employing clinical follow-up in a prospective, multicenter study.. This is an analysis of patients who started treatment with mirabegron between May and September 2014 and were evaluated 1year after treatment commenced. During this evaluation we determined how many patients stopped treatment and established their reasons for discontinuation.. 206 patients being treated for OAB with mirabegron were evaluated a year after starting treatment. It emerged that 60 patients (29.1%) had discontinued the treatment, citing the following reasons: 24/60 insufficient treatment efficacy, 26/60 other reasons, while 10 members of the group discontinued treatment because of side effects. 75 out of 206 patients were ≤60 years old and 28% terminated the study prematurely: 131 out of 206 were >60years old and 29.2% terminated the study prematurely. In the group of patients without previous OAB treatment 35.7% discontinued treatment with mirabegron, while 28.1% of patients with previous anticholinergic treatment discontinued treatment.. In our clinical prospective multicenter study, persistence in treatment with mirabegron reached a figure of 71%.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Medication Adherence; Middle Aged; Thiazoles; Urinary Bladder, Overactive; Young Adult

Persistence with antimuscarinic therapy in overactive bladder (OAB) is poor, but may be different for mirabegron, a β. To compare persistence and adherence with mirabegron versus tolterodine extended release (ER) and other antimuscarinics in routine clinical practice over a 12-mo period.. Retrospective, longitudinal, observational study of anonymised data from the UK Clinical Practice Research Datalink GOLD database. Eligibility: age ≥18 yr, ≥1 prescription for target OAB drug (between May 1, 2013 and June 29, 2014), and 12-mo continuous enrolment before and after the index prescription date.. Mirabegron, darifenacin, fesoterodine, flavoxate, oxybutynin ER or immediate-release (IR), propiverine, solifenacin, tolterodine ER or IR, and trospium chloride.. The primary endpoint was persistence (time to discontinuation). Secondary endpoints included 12-mo persistence rates and adherence (assessed using medication possession ratio, MPR). Cox proportional-hazards regression models and logistic regression models adjusted for potential confounding factors were used to compare cohorts. Analyses were repeated after 1:1 matching.. The study population included 21996 eligible patients. In the unmatched analysis, the median time-to-discontinuation was significantly longer for mirabegron (169 d, interquartile range [IQR] 41-not reached) compared to tolterodine ER (56 d, IQR 28-254; adjusted hazard ratio [HR] 1.55, 95% confidence interval 1.41-1.71; p<0.0001) and other antimuscarinics (range 30-78 d; adjusted HR range 1.24-2.26, p<0.0001 for all comparisons). The 12-mo persistence rates and MPR were also significantly greater with mirabegron than with all the antimuscarinics. Limitations include the retrospective design, use of prescription records to estimate outcomes, and inability to capture reasons for discontinuation.. Persistence and adherence were statistically significantly greater with mirabegron than with tolterodine ER and other antimuscarinics prescribed for OAB in the UK.. This study assessed persistence and adherence (or compliance) with medications prescribed for OAB in a large UK population. We found that patients prescribed mirabegron remained on treatment for longer and showed greater adherence than those prescribed traditional antimuscarinics.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Chi-Square Distribution; Databases, Factual; Drug Administration Schedule; Female; Humans; Kaplan-Meier Estimate; Logistic Models; Longitudinal Studies; Male; Medication Adherence; Middle Aged; Muscarinic Antagonists; Odds Ratio; Proportional Hazards Models; Retrospective Studies; Thiazoles; Time Factors; Treatment Outcome; United Kingdom; Urinary Bladder, Overactive; Urological Agents; Young Adult

Topics: Acetanilides; Double-Blind Method; Humans; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive

Overactive bladder syndrome (OAB) is a chronic and prevalent condition which has a negative impact on Quality of Life. The National Institute of Clinical Excellence issued two documents which give slightly varying algorithms of pharmacotherapy for OAB, offering mirabegron as a possible treatment in certain circumstances. In the absence of trials involving a direct comparison of therapies, an indirect comparison can provide useful information on the difference in treatment effects between competing interventions.. To compare effectiveness of available medical therapies for OAB using Bucher indirect treatment comparison (ITC) model.. A systematic literature search identified randomised controlled trials (RCT) assessing effectiveness of drugs for OAB versus placebo. Then indirect comparisons of the treatments effects were made, preserving the randomisation of the originally assigned patient groups, using Bucher method.. 25 RCTs met inclusion criteria. In keeping with ITC method validity, four assessments were undertaken of mirabegron against anticholinergics, which were number of incontinence episodes, micturition episodes, urgency episodes in 24 h and volume of micturition. This indirect treatment analysis suggests that mirabegron is as effective as anticholinergics in managing of OAB, except for solifenacin which appears to be superior.. These findings suggest that work looking into treatment choice should be individualized to patient characteristics rather than fitting patients to a treatment. Further work is required to identify what patient characteristics may be crucial and indicate that studies exploring the most effective sequence of managing treatment naïve patients and those with refractory disease.

Topics: Acetanilides; Cholinergic Antagonists; Humans; Quality of Life; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urination; Urological Agents

The β. An economic model with monthly cycles and a 1-year time horizon was developed to depict a treatment pathway for a hypothetical cohort of 100 patients with OAB. At model entry, patients receive mirabegron or an antimuscarinic. Patients who do not persist may switch treatment, undergo a minimally invasive procedure, or remain symptomatic (uncontrolled). The model includes direct costs (e.g. physician visits) and indirect costs (e.g. lost productivity). A one-way univariate sensitivity analysis assessed a ±20% variation in each of the key model inputs.. At 1 year, a greater proportion of patients persisted on treatment with mirabegron compared with antimuscarinics (33% vs 15-23%), and a smaller proportion switched treatment (17% vs 20-22%). The number of healthcare visits (292 vs 299-304), pads used (74,098 vs 77,878-81,669), and work hours lost (4,497 vs 5,372-6,249) were all lower for mirabegron vs antimuscarinics. The estimated total annual cost of treatment per patient with mirabegron was $2,127.46 Canadian dollars (CAD) ($5.82 CAD/day) compared with $2,150.20-$2,496.69 CAD ($5.89-$6.84 CAD/day) for antimuscarinics. The one-way sensitivity analysis indicated the results are robust.. Improved persistence observed in routine clinical practice with mirabegron appears to translate into benefits of reduced healthcare resource use, and lower direct and indirect costs of treatment compared with antimuscarinics. Overall, these data suggest that mirabegron may offer clinical and economic benefits for the management of patients with OAB in Canada.

Topics: Acetanilides; Canada; Humans; Medication Adherence; Models, Econometric; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive; Urological Agents

The discovery of vibegron, a potent and selective human β3-AR agonist for the treatment of overactive bladder (OAB), is described. An early-generation clinical β3-AR agonist MK-0634 (3) exhibited efficacy in humans for the treatment of OAB, but development was discontinued due to unacceptable structure-based toxicity in preclinical species. Optimization of a series of second-generation pyrrolidine-derived β3-AR agonists included reducing the risk for phospholipidosis, the risk of formation of disproportionate human metabolites, and the risk of formation of high levels of circulating metabolites in preclinical species. These efforts resulted in the discovery of vibegron, which possesses improved druglike properties and an overall superior preclinical profile compared to MK-0634. Structure-activity relationships leading to the discovery of vibegron and a summary of its preclinical profile are described.

Topics: Adrenergic beta-3 Receptor Agonists; Animals; CHO Cells; Cricetinae; Cricetulus; Drug Discovery; Female; Humans; Lipidoses; Microsomes, Liver; Models, Molecular; Pyrimidinones; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta; Serotonin Plasma Membrane Transport Proteins; Structure-Activity Relationship; Urinary Bladder; Urinary Bladder, Overactive; Urination; X-Ray Diffraction

The aim of this study was to evaluate for any association between pretreatment cystometry results and outcome of treatment with mirabegron in women with overactive bladder (OAB) symptoms.. This was a prospective observational study of women with OAB symptoms that proved refractory to conservative management. All women underwent filling and voiding subtraction cystometry prior to further treatment. Women were treated with mirabegron 50 mg once daily, and outcomes were evaluated after 6 weeks' treatment. The primary outcome measure was change in symptoms as indicated by response to the Patient Global Impression of Improvement (PGI-I) scale. The presence of detrusor overactivity (DO), the highest detrusor pressure recorded during the filling phase, the presence of urodynamic stress incontinence (USI), cystometric capacity, voided volume, maximum flow rate and detrusor pressure at maximum flow were all compared between responders and nonresponders.. The study population consisted of 169 women; response rate to mirabegron was 69.8 %. There was no association between the presence of DO or maximum detrusor pressure during filling and USI, cystometric capacity, maximum flow rate and detrusor pressure at maximum flow and treatment response. In a subgroup with OAB symptoms refractory to previous treatment with antimuscarinics, there was an association between the presence of DO and a positive treatment response (p = 0.02).. Overall, there is no association between urodynamic findings and response to treatment with mirabegron. This may reflect the fact that mirabegron's mode of action mechanisms are not measurable using cystometry. In women with refractory symptoms, however, the presence of DO is associated with a positive response to treatment.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Diagnostic Techniques, Urological; Female; Humans; Middle Aged; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

It is a retrospective chart analysis.. In patients with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI), neurogenic detrusor overactivity (NDO) can cause both deterioration of the upper urinary tract and urinary incontinence. Antimuscarinic treatment is frequently discontinued due to side effects or lack of efficacy, whereas injection of onabotulinumtoxin into the detrusor is a minimally invasive procedure with risks of urinary retention, infection and haematuria. Mirabegron, a new β-3 agonist, is a potential new agent for treatment of NDO. Aim of the study was to evaluate the efficacy of mirabegron in SCI patients with NLUTD.. Swiss Paraplegic Center, Nottwil, Switzerland.. A retrospective chart analysis of SCI patient treated with mirabegron.. Fifteen patients with NDO were treated with mirabegron for a period of at least 6 weeks. Significant reduction of the frequency of bladder evacuation per 24 h (8.1 vs 6.4, P=0.003), and of incontinence episodes per 24 h (2.9 vs 1.3, P=0.027) was observed. Furthermore, we observed improvements in bladder capacity (from 365  to 419 ml), compliance (from 28 to 45 ml cm(-1) H(2)0) and detrusor pressure during storage phase (45.8  vs 30 cm H(2)0). At follow-up, 9/15 patients were satisfied with the therapy, 4/15 reported side effects (3 × aggravation of urinary incontinence, 1 × constipation).. Mirabegron may evolve as an alternative in the treatment of NDO. We observed improvements in urodynamic and clinical parameters. Due to the limited number of patients and the retrospective nature of the study, prospective, placebo-controlled studies are necessary.

Topics: Acetanilides; Adult; Female; Follow-Up Studies; Humans; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Spinal Cord Injuries; Statistics, Nonparametric; Switzerland; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Urological Agents

Conclusive data comparing treatment efficacy of OAB pharmacotherapy in normal weight versus obese patients are not available. Obesity represents a risk factor for OAB/LUTS. We hypothesized that the effect of treatment with mirabegron might be diminished in obese patients.. One hundred sixty nine women were prescribed mirabegron, 50mg/day. Subjective and objective parameters were compared prior to and following three months of treatment. The study population was stratified into three groups according to a patients' BMI (A-normal weight, B-overweight, C-obese). We compared the change in parameters before and after treatment within each group. Subsequently the differences between groups were correlated. The same analysis was performed separately in patients who failed anticholinergic therapy (n=85). A paired t-test was used to compare the parameters before and after the procedure within groups, and a two-sample t-test was applied to conduct a comparison between groups. A p value of <0.05 was considered statistically significant.. Significant improvement (p<0.001) within all groups was observed in all parameters, with an exception in the number of severe urgency episodes per 24h (p=0.291) in Group B. We did not observe any statistically significant difference between groups A, B and C. The same trend has been observed in subgroup of patients, who did not respond previous antimuscarinic treatment.. This study provides evidence in support of previously documented data indicating good efficacy of mirabegron in the treatment of OAB. The data obtained do not confirm our hypothesis that the body weight influences the treatment outcome of mirabegron.

Topics: Acetanilides; Aged; Body Mass Index; Female; Humans; Middle Aged; Risk Factors; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Most published data on mirabegron relates to short-term clinical trials and suggest that it might be effective in controlling OAB and have low side effects. This study aimed to identify persistence with mirabegron, changes in symptoms and quality of life, and predictors of perseverance over 1 year.. The study was a large, prospective case series of 354 patients who were prescribed mirabegron for OAB between February 2013 and July 2014. At 1 year, patients filled out patient global impression of improvement, the International Consultation on Incontinence female lower urinary tract symptoms questionnaire (ICIQ-FLUTS) and PFDI questionnaires. The reasons for discontinuing treatment were identified.. Outcomes were available for 88 % of the cohort. Twenty five percent continued mirabegron therapy at 1 year with 26 % "very much better" and 37 % "much better". ICIQ-FLUTS (17.2-13.4; p = 0.002) and urinary distress inventory (UDI) (59.2-44.3; p < 0.001) scores demonstrated significant improvements from baseline (pre-treatment) compared with 1 year. The ICIQ-FLUTS "filling score" increased from 3.55 at 6 weeks to 5.27 at 1 year (p = 0.02) despite continuing mirabegron therapy. The most common causes of discontinuation were lack of efficacy (26 %) and side effects (10 %). Thirty-seven percent of the cohort was taking mirabegron in combination with an anticholinergic. Patients who were treatment naïve were more likely to discontinue mirabegron than those who had previously taken anticholinergics (p = 0.02).. Over two thirds of patients discontinue mirabegron therapy within 1 year. A significant proportion of patients were on combined therapy to control symptoms. The initial improvement in symptom scores seems to deteriorate. The improvements in quality of life are sustained in patients who persist with therapy.

Topics: Acetanilides; Adult; Aged; Cholinergic Antagonists; Drug Therapy, Combination; Female; Humans; Medication Adherence; Middle Aged; Prospective Studies; Quality of Life; Surveys and Questionnaires; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Antimuscarinics are the pharmacologic mainstay of overactive bladder (OAB) management, but side effects limit their use. Mirabegron, a new molecule with a distinct mechanism of action (β3-adrenoreceptor agonist), was recently approved as monotherapy for idiopathic OAB in adults but has not been studied in the pediatric population.. To evaluate the efficacy and safety of mirabegron to treat urinary incontinence in children with idiopathic OAB who were refractory to and/or intolerant of antimuscarinics.. A prospective off-label study using mirabegron was conducted. Pediatric patients without symptom improvement under behavioral and medical therapies and/or with significant side effects with at least two different antimuscarinic agents were recruited.. Our primary outcome was better reported efficacy than with the use of prior anticholinergic medication. Secondary end points were tolerability, safety, and satisfaction. Efficacy and tolerability were assessed with voiding diaries, postvoid residuals, urine cultures, electrocardiogram, and vital signs. Families were questioned for continence, side effects, compliance, and Patient Perception of Bladder Condition (PPBC) questionnaire. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis.. A total of 58 patients were recruited at a median age of 10.1 yr and were on mirabegron for a median of 11.5 mo. Median bladder capacity improved from 150ml to 200ml (p<0.001). Continence improved in 52 of 58, with 13 being completely dry. Median PPBC improved from 4.0 to 2.0 (p<0.001). Eight patients reported mild or moderate side effects. Absence of a placebo group is a limitation of the study.. Mirabegron, a novel first-in-class therapy, appeared as a safe and effective alternative for children with idiopathic OAB refractory to antimuscarinics.. We evaluated the efficacy and safety of mirabegron to treat incontinence in pediatric patients. Continence, median voided volumes, and quality of life were improved after the introduction of mirabegron, and few side effects were reported.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Child; Female; Humans; Male; Muscarinic Antagonists; Off-Label Use; Patient Satisfaction; Pilot Projects; Prospective Studies; Retreatment; Surveys and Questionnaires; Thiazoles; Treatment Failure; Urinary Bladder, Overactive; Urinary Incontinence

Mirabegron is the first β3-adrenoceptor selective agonist approved for the treatment of OAB. Many randomised controlled trials report outcomes that are difficult to interpret in usual clinical practice. The aim of our study is to evaluate the efficacy and tolerability of mirabegron as treatment option for OAB in an unselected patient population in daily clinical practice and to identify if any patient characteristics predicted patients response to therapy.. A prospective consecutive cohort of patients was studied between February 2013 and July 2014. Patients were prescribed Mirabegron 50mg once daily for 6 weeks. They were assessed at the initial appointment and at 6 weeks using validated questionnaires. The primary outcome measure was defined using the Patient Global Impression of Improvement Scale (PGI-I).. 317 women were prescribed mirabegron and 244 (77%) completed 6 weeks of drug therapy. Of those completing the course, 27 (11%) described themselves as "very much better" and a further 56 (23%) much better. There was significant symptom improvement based on the ICIQ-FLUTS long form scores from 19.7 to 16.2 (p<0.001) and urinary distress inventory from 68.6 to 61.3 (p<0.005). Twenty-three (8.6%) patients discontinued mirabegron prematurely due to side-effects. Thirty one (10%) did not attend follow up and 19 (6%) decided against taking the medication and did not use their prescription.. Mirabegron is a treatment option for patients with overactive bladder. Treatment benefits are modest but the discontinuation rate for side effects are low.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Female; Humans; Middle Aged; Prospective Studies; Surveys and Questionnaires; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To evaluate the cost-effectiveness of first-line treatment of Overactive Bladder (OAB) with fesoterodine relative to mirabegron, from the Spanish National Health System (NHS) perspective.. A decision tree model was developed to represent a typical clinical process of 52-week of treatment for an OAB patient with urge urinary incontinence (UUI) initiating first-line therapy with fesoterodine 4mg, including optional titration to 8mg, vs.mirabegron 50mg. Efficacy data were obtained from a Bayesian indirect treatment meta-analysis. Patients with UUI of less than one episode/day were defined as treatment responder and persistence was assessed at weeks 4, 12 and 24. At week 12, non-responders discontinued treatment permanently. Quality-adjusted life years (QALYs) were calculated based on time spent in responder and non-responder states. OAB-related drug and medical care costs including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections and depression) were modeled and expressed in €2015.. At week 52, the percentage of responders was 20.8% for patients starting on fesoterodine 4mg who optionally titrated to 8mg and 19.4% for patients treated with mirabegron. QALYs were slightly higher with fesoterodine than mirabegron (0.7703vs. 0.7668, difference=0.0035). Fesoterodine treatment also had slightly higher total costs than mirabegron (3,296€vs. 3,217, difference=79€), resulting in a cost of 22,523/QALY€ gained for fesoterodine versus mirabegron. Probabilistic sensitivity analysis confirmed the slight advantage of fesoterodine with a 61.1% probability of being cost-effective at the 30,000€ willingness-to-pay for 1QALY threshold.. Given the relatively small 1-year cost difference between the two treatments, fesoterodine can be considered a cost-effective option relative to mirabegron for the first-line management of OAB with UUI in Spain.

Topics: Acetanilides; Benzhydryl Compounds; Cost-Benefit Analysis; Delivery of Health Care; Female; Humans; Male; Middle Aged; Spain; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence, Urge

Topics: Acetanilides; Humans; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Topics: Acetanilides; Aged; Female; Humans; Male; Muscarinic Antagonists; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

To determine risks associated with prescribing mirabegron, the first-in-class β3-adrenoreceptor agonist, to non-selected female patients with overactive bladder.. Routine female patients seeking treatment for overactive bladder (n=221) in a urology/gynecology outpatient clinic. Data on adverse events, cardiovascular outcomes, condition specific symptoms and drug discontinuation was collected at two months follow-up (FU). Non-parametric statistics was used as appropriate. Odds ratios (ORs) with 95% confidence intervals (CIs) for outcome association analyses using logistic regression.. 16 patients (7.2%) discontinued treatment because of side effects. There were no significant associations between cardiovascular adverse events and pre-existing cardiovascular disease (OR 0.3, 95% CI 0.3-2.6), or pre-existing ECG abnormalities (OR 2.3, 95% CI 0.3-16.3). At FU ECGs there were no de novo cases of tachyarrhythmias and no significant difference in mean QTc between baseline (403ms, SD 21.7) and the 2 months follow-up ECG (403ms, SD 20.3) (p=0.75). There was a significant decrease in the mean systolic blood pressure (p=0.03) but no significant change in mean diastolic pressure (p=0.8) or heart rates (p=0.2) from baseline to FU. Overactive bladder specific symptoms and quality of life improved significantly (p<0.001 respectively).. Mirabegron treatment is associated with a satisfactory cardiovascular safety profile, as well as, significant symptomatic improvement also in a heterogeneous population of non-selected women with overactive bladder presenting in everyday clinical practice.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Cardiovascular Diseases; Cohort Studies; Drug Monitoring; Female; Follow-Up Studies; Humans; Medication Adherence; Middle Aged; Outpatient Clinics, Hospital; Prospective Studies; Quality of Life; Risk; Self Report; Severity of Illness Index; Sweden; Thiazoles; Urinary Bladder, Overactive; Urological Agents

The first class of oral pharmacologic treatments for overactive bladder (OAB) are antimuscarinics that are associated with poor persistence, anticholinergic adverse events, and increased anticholinergic burden (ACB) with risk of cognitive impairment. Mirabegron, a β3-adrenoceptor agonist, is an oral treatment that does not contribute to ACB and has early evidence of improved persistence. The objective of the analysis was to assess the cost-effectiveness of mirabegron for OAB vs six antimuscarinics in the US.. A Markov state-transition model assessed US commercial health-plan and Medicare Advantage perspectives over a 3-year time horizon in an OAB patient population. Transition probabilities between five micturition and five incontinence severity states were derived from a network meta-analysis of 44 trials of oral OAB treatments. Therapy beginning with an oral OAB agent could discontinue or switch to another oral agent and could be followed by tibial nerve stimulation, sacral neuromodulation, or onabotulinumtoxinA. The primary outcome was cost per quality-adjusted life year (QALY). Utilities were mapped from incontinence and micturition frequencies as well as demographics. Based on analysis of data from a large healthcare system, elevated ACB was associated with increased healthcare utilization and probability of cognitive impairment.. From both commercial and Medicare Advantage perspectives, mirabegron was the most clinically effective treatment, while oxybutynin was the least expensive. Tolterodine immediate release (IR) was also on the cost-effectiveness frontier. The analysis estimated costs per QALY of $59,690 and $66,347 for mirabegron from commercial health plan and Medicare Advantage perspectives, respectively, compared to tolterodine IR. Other antimuscarinics were dominated.. This analysis estimated that mirabegron is a cost-effective treatment for OAB from US commercial health plan and Medicare Advantage perspectives, due to fewer projected adverse events and comorbidities, and data suggesting better persistence.

Topics: Acetanilides; Cost-Benefit Analysis; Economics, Pharmaceutical; Female; Humans; Male; Markov Chains; Medicare Part C; Muscarinic Antagonists; Thiazoles; United States; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

Mirabegron is a β3-adrenoreceptor agonist developed for treatment of overactive bladder (OAB). α1-Adrenergic receptor blockers are effective for lower urinary tract symptoms (LUTS) in male patients. However, the efficacy of mirabegron additional treatment in elderly male patients with persistent male LUTS, especially in OAB after monotherapy with α1-adrenergic blockers, is not fully understood.. This study was conducted in male LUTS patients who were ≥ 65 years of age and had persistent OAB symptoms, regardless of whether they took an α1-adrenergic receptor blocker orally. Before and 12 weeks after mirabegron additional therapy (50 mg once daily), we evaluated the efficacy of this treatment using the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score (IPSS), and changes in the maximum flow rate (Qmax) and post-void residual urine volume (PVR). We evaluated patients overall and divided into two groups by age: young-old (from 65 to 74 years old) and old-old (from 75 to 84 years old).. Fifty men were enrolled in this study. Mirabegron additional therapy improved the total OABSS, total IPSS, and IPSS-quality of life (QOL) score. The voided volume (VV) and Qmax improved after treatment in patients overall. However, there was no significant change in PVR. The total OABSS, total IPSS, and IPSS-QOL score significantly improved in both of the young-old and old-old groups. However, a significant increasing of VV was detected in the young-old group. There were no significant differences in the Qmax or PVR in either group.. Mirabegron additional therapy was effective for male patients whose persistent LUTS and particularly OAB was not controlled with α1-adrenergic receptor blocker monotherapy, and mirabegron did not have negative effects on voiding function. Additionally, mirabegron additional therapy was considered effective regardless of patient age.. Trial registration number (TRN) trial registration number (TRN) and date of registration: ISRCTN16759097 in July 8, 2016.

Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Aged; Aged, 80 and over; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

The aim of this study was to evaluate if levels of gonadotropic and sex steroidal hormones influence the efficacy of mirabegron in the treatment of overactive bladder.. We included 58 female participants who received treatment with mirabegron 50 mg once daily and provided a blood sample for hormone profiling before treatment was initiated. Serum hormone concentrations for estradiol, progesterone, testosterone, FSH, LH, TSH, and T4 were analyzed. Urinary Distress Inventory (UDI), (overactive bladder domain: UDIOAB), and the short form Pelvic Floor Impact Questionnaire (PFIQ-7) were used to assess subjective outcomes.. There were significant overall improvements in UDI, UDIOAB, and the PFIQ from baseline to the 2 months of follow-up (P = 0.001, 0.001, and 0.008, respectively). The magnitude of the mean difference of improvements was similar between pre- and postmenopausal women. Estrogen levels were nonsignificantly lower in participants who experienced an improvement in UDI and UDIOAB at 2 months of follow-up as compared with those that did not (P = 0.7). There were no other clinically relevant differences in hormone levels in relation to improvements in UDI, UDIOAB, or PFIQ. In logistic regression analysis there were no associations between UDIOAB outcomes and age, previous use of anticholinergic drugs, parity, menopause, and local estrogen treatment.. Estradiol, gonadotropic hormones, thyroid hormones, and testosterone levels did not influence the clinical effects of mirabegron in women with overactive bladder. Menopause status should not be a determinant for mirabegron treatment.

Topics: Acetanilides; Aged; Dose-Response Relationship, Drug; Estradiol; Female; Follow-Up Studies; Gonadotropins; Humans; Logistic Models; Middle Aged; Prospective Studies; Testosterone; Thiazoles; Thyroid Hormones; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Double-Blind Method; Humans; Muscarinic Antagonists; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Oral pharmacological treatment for overactive bladder (OAB) consists of antimuscarinics and the beta-3 adrenergic agonist mirabegron. Antimuscarinic adverse events (AEs) such as dry mouth, constipation, and blurry vision can result in frequent treatment discontinuation rates, leaving part of the OAB population untreated. Antimuscarinics also contribute to a patient's anticholinergic cognitive burden (ACB), so the Beers Criteria recommends cautious use of antimuscarinics in elderly patients who take multiple anticholinergic medications or have cognitive impairment. Since mirabegron does not affect the cholinergic pathways, it is unlikely to contribute to a patient's ACB.. To estimate the health care costs associated with the pharmacological treatment of OAB with mirabegron and antimuscarinics from U.S. commercial payer and Medicare Advantage perspectives, using a budget impact model.. For this budget impact model, 2 analyses were performed. The primary analysis estimated the budgetary impact of increasing the use of mirabegron in a closed patient cohort treated with oral pharmacological treatments. The secondary analysis modeled the economic impact in an open cohort by allowing untreated patients to begin treatment with mirabegron after potential contraindication, intolerance, or lack of effectiveness of antimuscarinics. The analyses were performed over a 3-year time horizon. The economic impact of increased mirabegron use was quantified using direct medical costs, including prescription costs and health resource utilization (HRU) costs. Costs of comorbidities included pharmacy and medical costs of treating OAB-related urinary tract infections (UTI), skin rashes, and depression. An analysis of a large single-site integrated health network database was commissioned to quantify ACB-related HRU in terms of the increases in yearly outpatient and emergency department visits. Based on this analysis, the model associated each unit increase in ACB score with increased HRU and probability of mild cognitive impairment. Clinical outcomes of increased use of mirabegron were presented as the number of AEs and comorbidity episodes that could be avoided. One-way sensitivity analyses were performed to quantify the expected budget impact over the range of uncertainty for the key input variables.. Primary analysis calculated the impact of increasing the use of mirabegron from 4.5% to 5.3%, 7.1%, and 9.4% in years 1, 2, and 3, respectively, among oral pharmacological OAB treatments that included generic and branded antimuscarinics: oxybutynin, tolterodine, trospium, darifenacin, fesoterodine, and solifenacin. For a 1 million-member U.S. commercial payer plan, the total prescription costs increased, and the total medical costs decreased during the 3-year time horizon, yielding increases of $0.005, $0.016, and $0.031 from current per member per month (PMPM) costs and $0.90, $2.92, and $5.53 from current per treated member per month (PTMPM) costs, an average of less than 2% of current OAB treatment costs. For the Medicare Advantage plan, the resulting incremental PMPM costs were $0.010, $0.034, and $0.065, and the incremental PTMPM costs were $0.93, $3.04, and $5.76; all were less than 4% of the current cost. The secondary analysis estimated the budgetary effects of reducing the untreated population by 1% annually by initiating treatment with mirabegron. For a commercial payer, this resulted in PMPM cost increases of $0.156, $0.311, and $0.467 from the current value, while the incremental PTMPM cost increased by $6.17, $11.67, and $16.61. For the Medicare Advantage plan, the incremental increases in PMPM costs were $0.277, $0.553, and $0.830, and in PTMPM costs were $6.42, $12.15, and $17.29. Clinically, treating more OAB patients resulted in fewer OAB-related comorbidities from both health plan perspectives, since most events associated with nontreatment could be avoided. In the Medicare Advantage population of the secondary analysis, the total numbers of avoided events were predicted as 452 UTIs, 2,598 depression diagnoses, and 3,020 skin rashes during the time horizon of the model.. Mirabegron addresses an unmet need for therapy for certain OAB patients, for whom antimuscarinics are not recommended because of a risk of cognitive impairment and who are intolerant to the anticholinergic AEs. Using mirabegron involves moderate additional economic cost to a commercial or Medicare Advantage health plan for which medical cost savings can offset a substantial part of increased pharmacy costs.. Funding for this study was provided by Astellas. Perk, Wielage, T. Klein, and R. Klein are employed by Medical Decision Modeling, a contract research company that was paid to perform the described outcomes research and build the model contained in this study. Campbell and Perkins are employed by the Regenstrief Institute, which conducted a database analysis for this research. Campbell reports consultancy fees from Astellas, as well as pending grants from Merck, Sharpe, and Dohme Corp. Posta, Yuran, and Ng are employed by Astellas Pharma Global Development, the developer of mirabegron. Study concept and design were contributed by Perk, Wielage, R. Klein, and Ng. Campbell, T. Klein, and Perkins took the lead in data collection, assisted by Perk, Wielage, and Ng. Data interpretation was performed by Posta and Yuran, along with Perk, Wielage, R. Klein, Ng, Campbell, and Perkins. The manuscript was written by Perk and R. Klein, along with Wielage, T. Klein, Posta, Yuran, and Ng, and revised by all the authors.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Budgets; Health Care Costs; Humans; Insurance, Health; Medicare Part C; Middle Aged; Muscarinic Antagonists; Thiazoles; Treatment Outcome; United States; Urinary Bladder, Overactive; Urological Agents

To investigate urodynamic efficacy and safety of mirabegron add-on treatment with tamsulosin for Japanese male patients with overactive bladder (OAB).. A prospective study was conducted in 26 consecutive male patients with OAB who had been taking tamsulosin. OAB was diagnosed by overactive bladder symptom score (OABSS). Before and 8 weeks after mirabegron add-on treatment with preceding tamsulosin, we assessed OABSS, International Prostate Symptom Score (IPSS), free uroflowmetry (UFM), filling cystometry and pressure-flow study (PFS).. Mean age and prostate volume of the study patients were 75 ± 7 years and 32 ± 19 mL, respectively. Mirabegron significantly improved OABSS (from 8.5 ± 2.3 to 4.7 ± 2.5, P < 0.001). On free UFM, mirabegron significantly increased voided volume (from 135 ± 47 to 182 ± 102 mL, P = 0.01), maximum (from 10.7 ± 3.7 to 13.5 ± 6.4 mL/sec, P < 0.01) and average flow rate (from 5.5 ± 1.9 to 7.1 ± 3.3 mL/sec, P < 0.01), while postvoid residual urine volume did not change significantly (from 47 ± 38 to 63 ± 61 mL, P = 0.23). Before mirabegron, 24 patients (92%) had detrusor overactivity (DO). After mirabegron add-on, maximum cystometric capacity significantly increased from 170 ± 98 to 212 ± 95 mL (P = 0.01) and DO disappeared in six patients (25%). In the other 18 patients with persistent DO, amplitude of involuntary contraction decreased and bladder volume at first involuntary contraction increased with statistical significance. On PFS, detrusor pressure at maximum flow rate (from 79 ± 31 to 68 ± 19 cmH2 O, P = 0.10) or bladder contractility index (from 126 ± 39 to 120 ± 27, P = 0.45) did not change significantly.. Mirabegron add-on treatment with tamsulosin has efficacy and safety because it improves storage symptom without impairment of bladder contractility during voiding in male patients with OAB.

Topics: Acetanilides; Adrenergic beta-Agonists; Aged; Aged, 80 and over; Drug Therapy, Combination; Humans; Male; Middle Aged; Patient Safety; Prospective Studies; Sulfonamides; Tamsulosin; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urination; Urodynamics; Urological Agents

Mirabegron, which was the first β3-adrenoceptor agonist introduced for use in clinical practice, has been extensively evaluated in overactive bladder (OAB) patients in several phase II and III studies. However, most of the enrolled patients were treatment naive or had experienced a wash-out period before the introduction of mirabegron. No study has reported the treatment results of a direct switch from antimuscarinics to mirabegron, which may more commonly occur in clinical practice. This is an observational study to assess the therapeutic efficacy and safety of directly switching from antimuscarinics to mirabegron in patients with OAB receiving stable antimuscarinic treatment. Moreover, we sought to identify the patients who benefited more from the change.Patients aged ≥20 years with OAB receiving stable antimuscarinics for >3 months were enrolled. Antimuscarinics were discontinued in all patients and mirabegron 25 mg, once daily was initiated. Primary end-point was global response assessment (GRA) at 1 month after medication switching. Baseline parameters and parameters changed 1 month after medication switching were compared between patients with GRA ≥ 1 and GRA < 1.Of the 282 enrolled patients (209 men, 73 women; mean age, 74.4 years), 55.3% had better (GRA ≥ 1), 31.2% had similar (GRA = 0), and 10.3% had worse (GRA < 0) outcomes. The overall adverse events (AE) rate decreased from 24.1% to 12.8%. In overall patients, there was no significant improvement of OAB symptoms, but postvoid residual (PVR) urine decreased and voiding symptoms and quality of life index improved significantly. Patients with GRA ≥ 1 had significantly improved both storage and voiding symptoms. A total of 195 patients (69.1%) can maintain mirabegron without adding or resuming antimuscarinics for more than 3 months. Logistic regression analysis indicated that higher baseline OAB symptoms scores were predictor of satisfactory outcome.More than 50% patients exhibited better outcomes after switching from antimuscarinics to mirabegron. Significantly lower AE rates and decreased PVR were noted. Higher baseline OAB symptom scores may predict a better outcome.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Drug Substitution; Female; Humans; Male; Muscarinic Antagonists; Patient Satisfaction; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Aged; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Prospective Studies; Prostatic Hyperplasia; Receptors, Adrenergic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

The present paper presents, for the first time in Russia, a comparative pharmacoeconomic analysis of using mirabegron (Betmiga) to treat overactive bladder (OAB).. Three medical technologies were evaluated: treatment of OAB with mirabegron 50 mg/day, solifenacin 5 mg/day and solifenacin 10 mg/day. In addition, the strategies of mirabegron and botulinum toxin type A were analyzed as a result of simulating the second-line treatment.. When modeling for 1-year horizon, the lowest cost was found in mirabegron strategy, which was 16% lower than with solifenacin. When comparing the second line strategies using mirabegron and botulinum toxin type A, costs of mirabegron group were 61% lower. According to the selected performance criteria, mirabegron was more effective in comparison with other strategies. The findings of the budget impact analysis revealed that using mirabegron was preferable compared with solifenacin as the first line treatment, and compared with botulinum toxin type A as the second-line treatment. The analysis of cost-effectiveness and availability of technology showed growth when using mirabegron strategy; there was an increase in the efficiency of mirabegron strategy relative to solifenacin strategy, accompanied by cost reduction and, as a consequence, reducing the burden on the budget.. Thus, using mirabegron to treat OAB both as the first and the second line treatment is absolutely cost-effective and profitable medical technology.

Topics: Acetanilides; Costs and Cost Analysis; Delivery of Health Care; Humans; Models, Economic; Russia; Thiazoles; Urinary Bladder, Overactive

Mirabegron is a new beta 3 agonist for the treatment of overactive bladder (OAB). Although there are extensive data from randomised controlled trials, there is little real world evidence about its effectiveness and side effects. We conducted a prospective cohort study to evaluate the effectiveness of mirabegron as third-line treatment in patients with refractory OAB who did not benefit from antimuscarinic therapy and bladder drill.. The study was a prospective consecutive cohort of 67 women treated with mirabegron 50 mg. All the patients had symptoms of urgency with or without urgency incontinence and had failed to improve with bladder drill and at least one antimuscarinic medication. The outcomes were assessed after 6 weeks using the International Consultation of Incontinence Modular Questionnaire Short Form (ICIQ-SF), Patient Global Impression of Improvement (PGI-I) scale and Kings Health Questionnaire (KHQ).. The mean number of previous antimuscarinics was 2.81 (range 1-6). Forty out of 67 patients (60 %) described an improvement in their OAB. Responders demonstrated a significant improvement in 5 out of 10 domains of the KHQ. Similarly, the ICI-Q score improved from a mean of 12.7 (±5.3) to 9.2 (±5.3; p ≤ 0.008). Seven women (10 %) stopped mirabegron because of side effects.. This post-marketing surveillance study confirms that mirabegron improves clinical and quality of life outcomes in patients with OAB. The rate of side effects was low. This study supports mirabegron use as a third-line treatment for overactive bladder.

Topics: Acetanilides; Acetylcholine Release Inhibitors; Administration, Intravesical; Adrenergic beta-3 Receptor Agonists; Aged; Botulinum Toxins, Type A; Female; Humans; Middle Aged; Product Surveillance, Postmarketing; Prospective Studies; Retreatment; Severity of Illness Index; Thiazoles; Urinary Bladder, Overactive

To evaluate the costs and outcomes associated with different sequences of oral anti-muscarinic agents and the selective β(3)-adrenoceptor agonist, mirabegron, for the treatment of overactive bladder (OAB).. A Markov model with monthly cycle length and time horizon up to 3 years was designed to compare two different sequences of up to three lines of oral therapy for OAB. Patients who discontinued one oral medication could switch to another oral medication or could discontinue treatment. Patients whose symptoms were not controlled were considered for botulinum toxin or sacral nerve stimulation. Outcomes were measured by (a) number of patients with controlled symptoms (no incontinence episodes and <8 micturitions per 24 h); (b) patients with no incontinence episodes per 24 hours; and (c) patients with <8 micturitions per 24 h.. Including a third-line oral medication before considering other treatment options improved all patient outcomes, irrespective of the specific drugs used. A three-line sequence including two generic (oxybutynin first line and tolterodine extended-release second line) and one branded drug (solifenacin 5 mg third line) resulted in inferior patient outcomes at costs similar to a sequence of branded drugs (mirabegron first line, solifenacin 5 mg second line, solifenacin 10 mg third line): controlled patients (generic 29.6/1000 vs branded 38.7/1000); patients with no incontinence episodes (103.6/1000 vs 123.7/1000); patients with <8 micturitions (228.7/1000 vs 262.1/1000). Annual treatment costs per patient were similar (generic £1299 vs branded £1385).. In the treatment of OAB, low-cost generic treatments are not necessarily more cost-effective than branded drugs, primarily because a better efficacy and tolerability balance improves both symptom control and persistence.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Cost-Benefit Analysis; Health Services; Humans; Markov Chains; Muscarinic Antagonists; National Health Programs; Thiazoles; United Kingdom; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Acetylcholine Release Inhibitors; Adrenergic beta-3 Receptor Agonists; Botulinum Toxins, Type A; Cholinergic Antagonists; Humans; Thiazoles; Treatment Failure; Urinary Bladder, Overactive

Mirabegron is a new selective β3-adrenoreceptor agonist licensed for the treatment of overactive bladder (OAB). In clinical trials, mirabegron is well-tolerated with a low side-effect profile. There is little data available on the risks in a non-selected population. The presence of β-adrenoreceptors in cardiac and vascular tissue leads to the possibility of the development of adverse cardiovascular events. We conducted a consecutive cohort study to assess the risk of developing palpitations, the severity of the condition and to investigate any underlying risk factors that predispose patients with OAB to develop palpitations whilst taking mirabegron.. A consecutive cohort of patients with OAB was studied between February 2013 and June 2014. Patients were prescribed mirabegron 50mg daily and outcomes assessed at 6 weeks. Patients with known cardiac arrhythmias were excluded. In patients who developed palpitations, a detailed account of their symptoms and medical history were documented and a 12-lead electrocardiogram (ECG) was performed to assess heart rate, QT interval and the presence of any persisting arrhythmia was conducted.. A total of 279 patients were started on mirabegron. Eight patients (2.9%) reported palpitations whilst taking the drug. Two patients with a history of palpitations with no history of prolonged QT interval or arrhythmia on ECG developed worsening palpitations. The QTc was prolonged in two patients at 0.458 and 0.441s (QTc <420). Three patients developed chest pain or tightness. The palpitations resolved once therapy was stopped and did not result in serious adverse events such as hospitalisation.. Palpitations in an unselected population have a similar incidence to that demonstrated in previous drug trials. Palpitations may be associated with a worsening of cardiovascular dysfunction.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Cohort Studies; Electrocardiography; Female; Heart Rate; Humans; Middle Aged; Risk Factors; Thiazoles; Urinary Bladder, Overactive

To evaluate the clinical response and adverse events (AEs) of solifenacin (SOL) or mirabegron (MIR) in benign prostatic hyperplasia patients with persistent overactive bladder (OAB) symptoms after dutasteride (DUT) treatment.. Fifty cases with residual OAB symptom score (OABSS) ≥ 5 and OABSS Q3 ≥ 2 after at least 6 months treatment of DUT were included in this study. Patients were administered 5 mg/d of SOL (N = 25) or 50 mg/d of MIR (N = 25), and International Prostate Symptom Score (IPSS) and OABSS were prospectively collected at 4 and 12 weeks. The safety was evaluated by changes in postvoided residual urine volume and the incidence of AEs.. After DUT administration, the mean prostate volume, IPSS, and OABSS were 39.0 mL, 17.6, and 8.1, respectively. SOL 5 mg significantly reduced the IPSS, OABSS, and OABSS Q3 at 4 and at 12 weeks (-3.1, -2.7, -1.3; P <.05); however, 4 patients could not continue the SOL treatment owing to AEs. All patients could continue the 12 weeks of MIR treatment, and MIR 50 mg reduced IPSS and OABSS at 4 weeks and reduced IPSS, OABSS, and the OABSS Q3 (-3.0, -2.5, -0.9; P <.05) at 12 weeks. Postvoided residual urine volume increased by ≥ 100 mL after treatment in 2 cases in the SOL group but not in any patient in the MIR group.. Additional SOL or MIR might result in amelioration of the persistent OAB symptom after DUT treatment in patients with an enlarged prostate.

Topics: 5-alpha Reductase Inhibitors; Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Aged, 80 and over; Azasteroids; Dutasteride; Humans; Male; Middle Aged; Muscarinic Antagonists; Prospective Studies; Prostatic Hyperplasia; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Thiazoles; Urinary Bladder, Overactive

Mirabegron is used for the treatment of symptoms associated with overactive bladder syndrome. It selectively stimulates the β3 -adrenoreceptor, which relaxes the detrusor muscle. This improves urine storage by distension of the bladder body.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Neuromuscular Agents; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Cholinergic Antagonists; Comorbidity; Female; Humans; Medication Adherence; Randomized Controlled Trials as Topic; Thiazoles; Urinary Bladder, Overactive; Urological Agents; Women's Health

The objective of this monitoring was to evaluate persistence in the treatment of patients with overactive bladder syndrome (OAB) using mirabegron.. Prospective clinical study.. 10 gynecological and urological departments in CZE.. This is an analysis of a prospective, multicenter monitoring which started in May 2014 and will continue for 1 year. This monitoring included patients 18 years old who have had symptoms of OAB for minimum 3 months. The patient check-up was performed 6 months (±2 weeks) after the first visit. The dosage of mirabegron was 50 mg per day. For the evaluation the treatment efficacy we employed the TS-VAS and PPBC. During the check-up it was ascertained how many patients discontinued the treatment with mirabegron, and reasons for this interruption were established. The statistics were calculated using the software SPSS 20.0.. A prospective monitoring was performed on 206 patients. Their mean age was 62.8 years (range 23-89); mean body mass index for the whole group of patients was 27.3. At the check-up 6 months post-initiation of treatment it emerged that 55/206 (27%) patiens had discontinued the treatment. The reasons for discontinuation of treatment were: 24/55 (43%) insufficient treatment efficacy, 29/55 (53%) other reasons (the main reasons here were hospitalisation, surgery, gravidity) and 2/55 discontinued therapy because of side effects. The side effects were tachycardia, eye irritation, lower abdominal pain and vasculitis, and they were mild in nature. The termination of the study was 7/28 (25%) in the group of patients without previous treatment before mirabegron. Discontinuation of the treatment in the group of patients with previous anticholinergic treatment was 48/178 (27%). At the evaluation of the efficacy of the treatment during the check-up 6 months after initiation of treatment the mean TS-VAS was 77.5, a decrease of the scale of bothers evaluated by PPBC before treatment from a mean value of 3.56 to a value of 1.77.. Our hypothesis, that persistence in treat-ment with mirabegron would be relatively high due to reduced side effects and better cure effect, was confirmed, and this is the reason for higher rates of persistence in the treatment at 6 months check-up (73%).

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Body Mass Index; Cholinergic Antagonists; Female; Humans; Male; Middle Aged; Patient Compliance; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Patient Preference; Randomized Controlled Trials as Topic; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents; Xerostomia

Mirabegron, a first-in-class selective oral β3-adrenoceptor agonist, has similar efficacy to most antimuscarinic agents and a lower incidence of dry mouth in patients with overactive bladder (OAB).. To evaluate the cost-effectiveness of mirabegron 50 mg compared with oral antimuscarinic agents in adults with OAB from a UK National Health Service perspective.. A Markov model including health states for symptom severity, treatment status, and adverse events was developed. Cycle length was 1 month, and the time horizon was 5 years. Antimuscarinic comparators were tolterodine extended release, solifenacin, fesoterodine, oxybutynin extended release and immediate release (IR), darifenacin, and trospium chloride modified release. Transition probabilities for symptom severity levels and adverse events were estimated from a mirabegron trial and a mixed treatment comparison. Estimates for other inputs were obtained from published literature or expert opinion. Quality-adjusted life-years (QALYs) and total health care costs, including costs of drug acquisition, physician visits, incontinence pad use, and botox injections, were modeled. Deterministic and probabilistic sensitivity analyses were performed.. Base-case incremental cost-effectiveness ratios ranged from £367 (vs. solifenacin 10 mg) to £15,593 (vs. oxybutynin IR 10 mg) per QALY gained. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of £20,000/QALY gained, the probability of mirabegron 50 mg being cost-effective ranged from 70.2% versus oxybutynin IR 10 mg to 97.8% versus darifenacin 15 mg. A limitation of our analysis is the uncertainty due to the lack of direct comparisons of mirabegron with other agents; a mixed treatment comparison using rigorous methodology provided the data for the analysis, but the studies involved showed heterogeneity.. Mirabegron 50 mg appears to be cost-effective compared with standard oral antimuscarinic agents for the treatment of adults with OAB from a UK National Health Service perspective.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Bayes Theorem; Comparative Effectiveness Research; Computer Simulation; Cost-Benefit Analysis; Decision Support Techniques; Drug Costs; Health Resources; Humans; Markov Chains; Models, Economic; Muscarinic Antagonists; Patient Selection; Quality of Life; Quality-Adjusted Life Years; Severity of Illness Index; State Medicine; Thiazoles; Time Factors; Treatment Outcome; United Kingdom; Urinary Bladder; Urinary Bladder, Overactive

Antimuscarinic medications have long been the mainstay of drug treatment for overactive bladder. This article describes mirabegron, one of a new class of agents that relaxes the detrusor muscle directly via a beta3 adrenoceptor agonist. Mirabegron's efficacy on frequency, urgency, and urge incontinence was tested in several trials before its wide clinical introduction. However, caution is still needed as data are lacking on the drug's efficacy and safety in frail older adults and for long-term therapy.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Cytochrome P-450 CYP2D6 Inhibitors; Drug Interactions; Humans; Hypertension; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Bariatric Surgery; Cystitis, Interstitial; Female; Gynecology; Humans; Muscarinic Antagonists; Obesity; Pelvic Floor Disorders; Thiazoles; Urinary Bladder, Overactive; Urology

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Female; Humans; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Female; Humans; Male; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Drug Interactions; Humans; Receptors, Adrenergic, beta-3; Thiazoles; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urination; Urodynamics

Five new drugs that are used for medical problems often experienced by the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

Topics: Acetanilides; Aged; Bronchodilator Agents; Constipation; Drug Approval; Glaucoma; Humans; Peptides; Prostaglandins F; Thiazoles; United States; Urinary Bladder, Overactive

Mirabegron, a weak-basic compound, is a potent and selective β3-adrenoceptor agonist for the treatment of overactive bladder. Mirabegron extended release formulation shows dose-dependent oral bioavailability in humans, which is likely attributable to saturation of intestinal efflux abilities leading to higher absorption with higher doses. This study evaluated the membrane permeability of mirabegron and investigated the involvement of human intestinal transport proteins in the membrane permeation of mirabegron. Transcellular transport and cellular/vesicular uptake assays were performed using Caco-2 cells and/or human intestinal efflux (P-glycoprotein [P-gp], breast cancer resistance protein [BCRP], and multidrug resistance associated protein 2 [MRP2]) and influx (peptide transporter 1 [PEPT1], OATP1A2, and OATP2B1) transporter-expressing cells, vesicles, or Xenopus laevis oocytes. The absorptive permeability coefficients of mirabegron in Caco-2 cells (1.68-1.83 × 10(-6) cm/s) at the apical and basal pH of 6.5 and 7.4, respectively, were slightly higher than those of nadolol (0.97-1.41 × 10(-6) cm/s), a low permeability reference standard, but lower than those of metoprolol and propranolol (both ranged from 8.49 to 11.6 × 10(-6) cm/s), low/high permeability boundary reference standards. Increasing buffer pH at the apical side from 5.5 to 8.0 gradually increased the absorptive permeation of mirabegron from 0.226 to 1.66 × 10(-6) cm/s, but was still less than the value in the opposite direction (11.0-14.2 × 10(-6) cm/s). The time- and concentration-dependent transport of mirabegron was observed in P-gp-expressing cells and OATP1A2-expressing oocytes with apparent Km values of 294 and 8.59 μM, respectively. In contrast, no clear BCRP-, MRP2-, PEPT1-, or OATP2B1-mediated uptake of mirabegron was observed in their expressing vesicles or cells. These findings suggest that mirabegron has low-to-moderate membrane permeability and P-gp is likely to be involved in its efflux into the lumen in the intestinal absorption process. The results also suggest that mirabegron could possibly be transported by intestinal influx transporters as well as simple diffusion.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Biological Availability; Biological Transport, Active; Caco-2 Cells; Cell Membrane Permeability; Female; HEK293 Cells; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; LLC-PK1 Cells; Neoplasm Proteins; Oocytes; Organic Anion Transporters; Peptide Transporter 1; Recombinant Proteins; Swine; Symporters; Thiazoles; Urinary Bladder, Overactive; Xenopus laevis

Analysis of EQ-5D data often focuses on changes in utility, ignoring valuable information from other parts of the instrument. The objective was to explore how the utility index, EQ-5D profile, and EQ-VAS captured change in clinical trials of mirabegron, a new treatment for overactive bladder (OAB).. Data were pooled from three phase III clinical trials that investigated the efficacy and safety of mirabegron vs placebo. Tolterodine ER 4 mg was included as an active control in one study: (1) placebo, mirabegron 50 mg and 100 mg, and tolterodine 4 mg ER; (2) placebo, mirabegron 50 mg and 100 mg; (3) placebo, and mirabegron 25 mg and 50 mg. Data were collected at baseline, week 4, 8, and 12.. Analyses were performed on full analysis and modified intention to treat (ITT) data sets using UK utilities. Analysis controlled for relevant patient characteristics. Analysis of Covariance identified changes from baseline at each time point in utilities and EQ-VAS. Areas Under the Curve were estimated to summarize inter-temporal differences in effect. EQ-5D profile data were analysed using the Paretian Classification of Health Change.. In modified ITT analyses, mirabegron 50 mg was superior to tolterodine 4 mg in changes from baseline utilities after 12 weeks (p < 0.05); similarly, AUC results showed mirabegron 50 mg to be superior to tolterodine (p < 0.05) and placebo (p < 0.05) with the benefit already apparent at 4 weeks (p < 0.05). EQ-VAS more consistently indicated superior outcomes: all three mirabegron doses showed statistically significant greater effectiveness compared to tolterodine at 12 weeks. Individual EQ-5D dimensions and the overall profile showed no significant differences between study arms.. Mirabegron showed quicker and superior improvement in HR-QoL compared to tolterodine 4 mg ER. A limitation of the study is that EQ-5D was a secondary outcome in the pivotal trials, which were not powered to measure differences on EQ-5D.

Topics: Acetanilides; Analysis of Variance; Benzhydryl Compounds; Clinical Trials, Phase III as Topic; Cresols; Data Interpretation, Statistical; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Psychometrics; Quality-Adjusted Life Years; Sickness Impact Profile; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Female; Humans; Male; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Afferent Pathways; Biomarkers; Botulinum Toxins; Carbolines; Humans; Lower Urinary Tract Symptoms; Phosphodiesterase 5 Inhibitors; Signal Transduction; Tadalafil; Thiazoles; Urinary Bladder, Overactive; Urothelium

The β3-adrenoceptor (AR) agonist mirabegron has been introduced as a treatment for the overactive bladder. Its effects on the function of the ischemic bladder are not known.. To investigate the effect of mirabegron in a rat model of chronic ischemia-related bladder dysfunction.. Male Sprague-Dawley rats were divided into three groups: control (n=10), arterial endothelial injury (AI; n=16), and AI with mirabegron treatment (AI-mirabegron; n=10). AI and AI-mirabegron groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet following AI. AI-mirabegron rats received mirabegron (10mg/kg/d) orally for 8 wk. The control group received a regular diet.. After 8 wk, urodynamic investigation was performed in awake animals. Pharmacologic in vitro studies and histologic examination of the iliac arteries and bladders were performed.. Iliac arteries from both AI and AI-mirabegron rats displayed neointimal formation and luminal occlusion. Micturition interval (MI), bladder capacity (Bcap), and voided volume (VV) in the AI group were significantly less than in the control group (p<0.01). In the AI-mirabegron group, MI, Bcap, and VV were significantly larger than in the AI group (p<0.05) but significantly less than in the control group (p<0.05). Contractile responses of bladder strips to potassium chloride, electrical field stimulation, and carbachol were significantly lower after AI than in controls; responses in preparations from AI-mirabegron-treated animals were similar to those of controls. The AI group showed a significantly higher percentage of collagen (28.6 ± 1.57%) compared with the controls (8.65 ± 0.67%) and AI-mirabegron-treated animals (17.2 ± 2.32%). The mirabegron dose used in this study may potentially limit the translational value of the results.. In the chronically ischemic rat bladder, treatment with mirabegron seems to protect bladder function and morphology, resulting in reduced bladder hyperactivity. If the results are valid for humans, they support β3-AR agonism as a potential treatment of chronic ischemia-related bladder dysfunction.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Cholesterol, Dietary; Chronic Disease; Collagen; Disease Models, Animal; Dose-Response Relationship, Drug; Iliac Artery; Ischemia; Male; Neointima; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-3; Thiazoles; Time Factors; Urinary Bladder; Urinary Bladder, Overactive; Urination; Urodynamics; Vascular System Injuries

Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in men. Patients with BPH often present with a combination of obstructive and overactive bladder (OAB) symptoms. It is postulated that bladder outlet obstruction (BOO) from BPH results in concomitant OAB symptoms through ischemic induced variations in the response to neurotransmitters of both the detrusor and the urothelium. This altered response leads to the pathologic activation of the micturition reflex, generating sensory dysfunction and involuntary bladder contractions. Alpha-1 adrenoceptor antagonists (alpha-blockers) and 5-alpha reductase inhibitors (5-ARIs) are commonly used to treat the BOO caused by BPH. Anticholinergic agents are frequently used to treat concurrently OAB symptoms caused by the BOO. Unfortunately, anticholinergic medications demonstrate bothersome side effects and a theoretical risk of urinary retention. Basic science and clinical research has led to the development of a new class of pharmaceuticals for the treatment of overactive bladder with diminished risk of urinary retention and lacking many anticholinergic side effects. This novel compound, mirabegron (Mybertriq, Astellas Pharma US, Inc.), is a β₃-adrenoceptor agonist and represents a promising new class of oral agents designed for the treatment of OAB symptoms, with minimal effect on voiding.

Topics: 5-alpha Reductase Inhibitors; Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Humans; Lower Urinary Tract Symptoms; Male; Nocturia; Prostatic Hyperplasia; Prostatism; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Urinary incontinence, the involuntary leakage of urine, can result from abnormalities of the urinary tract or may be caused by other conditions and is sub-divided into a number of classifications including stress incontinence and urge urinary incontinence.(1) Urge urinary incontinence (UUI) is involuntary urine leakage accompanied by urgency of micturition.(2) Overactive bladder (OAB) syndrome is defined as urgency occurring with or without UUI and usually occurs with frequency and nocturia.(1) Wet OAB is associated with UUI, while dry OAB is not associated with incontinence. Current drug therapy for OAB involves the use of an antimuscarinic drug, of which there are a number available, such as oxybutynin, darifenacin, solifenacin and tolterodine.(1,3) ▾Mirabegron is the first of a new class of drug, beta-3-adrenoreceptor agonists, licensed for symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in adult patients with OAB syndrome.(4) Here we review the evidence for mirabegron.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Female; Humans; Male; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence, Urge

In the present study, we investigated the efficacy of mirabegron, a β3-adrenergic agonist, in patients aged ＞70 years who did not respond to treatment with an anticholinergic agent. From February 2012 to May 2012, we examined 37 patients who did not respond to treatment with an anticholinergic agent. We assessed the overactive bladder symptom score (OABSS), thirst, and constipation at baseline, as well as at 3 and 6 months from the start of drug administration. Theme an age of the female patients was 79.9±6.08 years. The OABSS indicated significant improvement in nocturia and urge incontinence at 3 and 6 months. Furthermore, mirabegron significantly relieved thirst (in 95.2% of cases) and constipation (in 87.5% of cases). Thus, mirabegron is considered useful for female patients aged ＞70 years who did not respond to treatment with an anticholinergic agent.

Topics: Acetanilides; Adrenergic beta-2 Receptor Agonists; Age Factors; Aged; Aged, 80 and over; Cholinergic Antagonists; Drug Substitution; Female; Humans; Muscarinic Antagonists; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Benzhydryl Compounds; Cresols; Female; Humans; Male; Muscarinic Antagonists; Phenylpropanolamine; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

To investigate the pharmacological properties of mirabegron in in vitro and in vivo, the effects on cAMP accumulation in Chinese hamster ovary (CHO) cells expressing rat β-adrenoceptors, the relaxant activity in isolated rat bladder smooth muscle, and the voiding effects in cerebral infarcted rats were evaluated. Mirabegron increased cAMP accumulation with EC(50) value and intrinsic activity of 19 nmol/L and 1.0, respectively, in CHO cells expressing rat β(3)-adrenoceptors. The EC(50) values and the intrinsic activities of mirabegron were 610 nmol/L and 0.6 for rat β(1)-adrenoceptors and were sumless and 0.1 for β(2)-adrenoceptors, respectively. Mirabegron showed concentration-dependent relaxant and full agonistic effects in rat bladder strips under passive tension with EC(50) value of 290 nmol/L. The concentration-response curve of mirabegron was affected neither by the β(1)-adrenoceptor selective antagonist CGP-20712A nor by the β(2)-adrenoceptor selective antagonist ICI-118,551. In in vivo studies with cerebral infarcted rats, a significant decrease in the volume voided per micturition compared with sham-operated rats was observed. Mirabegron dose-dependently increased the volume voided per micturition. In conclusion, we have extended the selectivity profile of mirabegron to rats and demonstrated that it is effective via stimulation of β(3)-adrenoceptors in a rat cerebral infarction model of detrusor overactivity.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Cerebral Infarction; CHO Cells; Cricetinae; Cricetulus; Cyclic AMP; Dose-Response Relationship, Drug; Humans; Male; Muscle, Smooth; Rats; Rats, Wistar; Receptors, Adrenergic, beta-3; Thiazoles; Transfection; Urinary Bladder; Urinary Bladder, Overactive

β(3)-Adrenoceptors are major players in detrusor relaxation and have been suggested as a new putative target for the treatment of overactive bladder syndrome. We determined the effects of mirabegron (YM178), a novel β(3)-adrenoceptor agonist, on carbachol-induced tone in isolated human detrusor preparations from patients with bladder outflow obstruction (BOO) with and without detrusor overactivity (DO), and from patients with normal bladder function. We compared the effects to those of isoprenaline, a non-selective β-adrenoceptor agonist. Detrusor specimens were obtained from patients with benign prostatic hyperplasia undergoing cystoscopy and from patients undergoing radical prostatectomy/cystectomy (in total 33 donors). Detrusor contractility was evaluated by organ bath studies and strips were incubated with carbachol (1μM) to induce and enhance tension. Both mirabegron and isoprenaline reduced carbachol-induced tone in tissues from all groups. Isoprenaline decreased tension with higher potency than mirabegron in normal, BOO and BOO+DO detrusor strips with pIC(50) values of 7.49 ± 0.16 vs. 6.23 ± 0.26 (P=0.0002), 6.89 ± 0.34 vs. 6.04 ± 0.31 (P=0.01), and 6.57 ± 0.20 vs. 5.41 ± 0.08 (P<0.0001, n=4), respectively. The maximal relaxant effect of isoprenaline and mirabegron in the normal, BOO and BOO+DO detrusor was 37.7 ± 14.4% and 36.1 ± 23.3%, 14.4 ± 12.2% vs. 33.4 ± 21.0% and 18.3 ± 10.0% vs. 28.3 ± 12.2% (n=4, P>0.05), respectively. Mirabegron and isoprenaline reduced carbachol-induced tone in both normal bladders and obstructed bladder with and without DO. Isoprenaline had higher potency than mirabegron, but the efficacy of mirabegron effect was the same as that of isoprenaline.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Agonists; Aged; Aged, 80 and over; Carbachol; Humans; In Vitro Techniques; Inhibitory Concentration 50; Isoproterenol; Male; Middle Aged; Muscle Contraction; Thiazoles; Urinary Bladder; Urinary Bladder Neck Obstruction; Urinary Bladder, Overactive

Overactive bladder (OAB) syndrome is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urge urinary incontinence, in the absence of urinary tract infection or other obvious pathology. Mirabegron (YM-178, Betanis®) is a novel, once-daily, orally active, first-in-class selective β(3)-adrenoceptor agonist that improves symptoms associated with OAB by enhancing storage function and relaxing the urinary bladder. Mirabegron has been approved in Japan for the indication of urgency, urinary frequency and urge urinary incontinence associated with OAB, and was recently submitted for approval to U.S. and European authorities for the same indication. In phase III clinical trials performed in Europe, the U.S. and Australia, mirabegron at doses of 50 or 100 mg for 12 weeks significantly decreased the mean number of incontinence episodes and micturition episodes per 24 hours, and was safe and well tolerated. Mirabegron may be an alternative in patients with OAB who are poor responders to antimuscarinic agents or intolerant of their adverse effects.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Interactions; Humans; Thiazoles; Urinary Bladder, Overactive

Experimental urethral obstruction in rats alters micturition patterns with non-voiding activity (NVA) during filling cystometry, showing similarity to that observed in human detrusor overactivity. Several drug classes with therapeutic potential in overactive bladder in humans have been tested in this model in rats, rabbits or guinea pigs, but no detailed analysis of drug effects on cystometric patterns has been published. The present study uses a rat model of overactivity with partial bladder outflow obstruction (BOO) in combination with the procedures to analyse NVA to study the effects of the anticholinergic drug tolterodine and the novel β(3)-adrenoceptor agonist mirabegron. The current data for the first time show that NVA in rats with BOO is sensitive to both the muscarinergic antagonist tolterodine and the β(3)-adrenoceptor agonist mirabegron, but with clear differences between the two drugs: during progression of bladder filling, tolterodine affected both the amplitude and frequency of NVA whereas mirabegron affected primarily the frequency. In addition, tolterodine dose-dependently reduced voiding contractions, while mirabegron did not. A model is proposed to account for these observations where both agents act on a 'pacemaker-like' mechanism which is sensitive to cholinergic excitatory and beta-adrenergic inhibitory inputs. Such concepts could provide insights into the nature of overactive bladder and the site of action of key therapeutic drugs.. To investigate the hypothesis that tolterodine and the β(3)-adrenoceptor agonist mirabegron exert their actions on the motor component of the motor/sensory system in the bladder wall: non-voiding activity (NVA).. The present study used standard cystometric techniques and a conscious rat model of partial bladder outflow obstruction (BOO). A single dose of either tolterodine (0.01, 0.1 0.3 or 1.0 mg/kg) or mirabegron (0.03, 0.1, 0.3, 1.0 or 3.0 mg/kg) was given i.v. to each animal.. In the dose ranges used, tolterodine reduced the voiding contraction amplitude, whereas mirabegron did not. Non-voiding activity consisted of small (<0.6 mmHg) and large (>0.6 mmHg) transients. As a fill progressed, both tolterodine and mirabegron reduced the cumulative activity of the large non-voiding contractions, but had little effect on the small transients. Tolterodine affected both the amplitude and frequency of NVA, whereas mirabegron affected primarily the frequency.. Non-voiding activity is sensitive to muscarinergic antagonists and β(3)-adrenoceptor agonists, but there are clear differences between the two drugs. A model is proposed to account for these observations where both agents act on a 'pacemaker-like' mechanism with cholinergic excitatory and adrenergic inhibitory inputs. Such concepts may provide insights into the nature of overactive bladder and the site of action of key therapeutic drugs.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Benzhydryl Compounds; Cresols; Dose-Response Relationship, Drug; Female; Infusions, Intravenous; Muscarinic Antagonists; Phenylpropanolamine; Rats; Rats, Sprague-Dawley; Thiazoles; Tolterodine Tartrate; Urinary Bladder Neck Obstruction; Urinary Bladder, Overactive; Urination

Topics: Acetanilides; Adrenergic beta-Agonists; Drug Approval; Humans; Receptors, Adrenergic, beta-3; Thiazoles; United States; United States Food and Drug Administration; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Drug Interactions; Humans; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Adenine; Anti-Retroviral Agents; Carbamates; Constipation; Deoxycytidine; Drug Combinations; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Organophosphonates; Peptides; Quinolones; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Drug Therapy, Combination; Humans; Thiazoles; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Aprepitant; Female; Humans; Morpholines; Pyrazoles; Receptors, Neurokinin-1; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics