pyrimidinones and Urinary-Bladder--Overactive

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

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

Vibegron is a new β3-adrenergic receptor agonist which has been demonstrated for the treatment of overactive bladder (OAB). We carried out meta-analysis to evaluate the efficiency of vibegron vs antimuscarinic monotherapy for treating OAB.. Randomized controlled trials (RCTs) of Vibegron vs antimuscarinic monotherapy for OAB were searched systematically by using EMBASE, MEDLINE, and the Cochrane Controlled Trials Register. The RevMan version 5.3.0. was used to analysis the data.. Three RCTs involving a total of 1751 patients were studied in the Systematic review and Meta-analysis. Efficacy end points: the mean number of micturitions episodes/d (P = .16); the mean number of urgency episodes/d (P = .05); mean number of urgency incontinence episodes/d (P = .11) and mean number of incontinence episodes/d (P = .14) indicated that vibegron and antimuscarinic had no significant differences in terms of OAB treatment. Mean volume voided/micturition showed a distinct difference in the two groups (P = .009). With regard to dry mouth and drug related treatment-emergent adverse event (TEAE), vibegron showed better tolerance than antimuscarinic. Serious adverse event (SAE) and discontinuations due to adverse event (AE) did not show a significant difference between the two groups.. The therapeutic effect of vibegron is similar to that of antimuscarinic, but vibegron does not increase the risk of AE.

Topics: Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive

Vibegron is a new kind of β3-adrenergic receptor agonist. We performed a systematic review and pooled analysis to assess the efficacy, safety, and tolerability of Vibegron for treating overactive bladder (OAB).. MEDLINE, the Cochrane Controlled Trial Register and EMBASE were used to pick out randomized controlled trials (RCTs) of Vibegron in treating OAB. The reference lists of the retrieved articles were also studied. We used RevMan version 5.3.0. to analyze the data.. Three high-quality RCTs involving a total of 2120 OAB patients were adopted in the systematic review and pooled analysis. The mean number of micturitions episodes/d (mean difference [MD] = -0.77; 95% confidence interval [CI] = -1.0 to -0.55; P < .00001); the mean number of urgency episodes/d (MD = -0.77; 95% CI = -1.03 to -0.52; P < .00001); mean number of urgency incontinence episodes/d (MD = -0.50; 95% CI = -0.64 to -0.35; P < .00001); mean number of incontinence episodes/d (MD = -0.45; 95% CI = -0.66 to -0.25; P < .0001); and mean volume voided/micturition (MD = 22.22; 95% CI = 17.36 to 27.07, P < .00001) showed that Vibegron was more efficacy in treating OAB than placebo. Dry mouth, drug-related treatment-emergent adverse event (TEAE), serious adverse event (SAE), and discontinuations due to adverse event (AE) suggested that Vibegron was well tolerated.. Our systematic review and pooled analysis demonstrate that Vibegron 75 mg or 100 mg/d statistically significant improved OAB symptoms. The treatment was well-tolerated, with a favorable safety profile.

Topics: Adrenergic beta-3 Receptor Agonists; Double-Blind Method; Humans; Pyrimidinones; Pyrrolidines; Randomized Controlled Trials as Topic; Treatment Outcome; Urinary Bladder, Overactive; Urination

The efficacy and safety of vibegron, which is a novel β3-adrenoceptor agonist, need to be systematically evaluated in the treatment of overactive bladder (OAB) patients. This study aimed to assess, using meta-analytic methods, the efficacy and safety of vibegron for OAB compared with placebo or antimuscarinics, considering all available data from comparative studies.. A systematic search was performed on MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials database to identify studies from their date of inception before 15 March 2020. Meta-analysis was performed based on eligible studies.. Six studies derived from four clinical trials with 4314 randomized patients were finally included in our analysis. We found that vibegron 50 mg and 100 mg were both significantly more efficacious than placebo for all efficacy outcomes. Furthermore, no significant differences were found between vibegron 50 mg or 100 mg and placebo for all the AEs assessed. In addition, the efficacy between vibegron 50 mg or 100 mg and antimuscarinics were comparable except for voided volume. Moreover, vibegron was associated with a decreased risk of dry mouth and an increased risk of nasopharyngitis versus antimuscarinics. Our study also demonstrated that the vibegron 50 mg and 100 mg were equally effective and safe across all the efficacy and AEs' outcomes.. Vibegron is effective and safe for treating patients with OAB. Based on the current evidence, we recommended that the initial use of vibegron 50 mg was the optimal algorithm in the pharmacologic management of OAB.

Topics: Algorithms; Humans; Pyrimidinones; Pyrrolidines; 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

The international phase 3 EMPOWUR trial demonstrated efficacy and safety of vibegron, a newer β 3 -adrenergic receptor agonist, in adults with overactive bladder (OAB). Women are disproportionately affected by OAB, especially those with bothersome symptoms, such as urge urinary incontinence (UUI).. This subgroup analysis from EMPOWUR assessed efficacy and safety of vibegron in women.. In EMPOWUR, patients with OAB were randomized 5:5:4 to 12 weeks of treatment with once-daily vibegron 75 mg, placebo, or tolterodine 4-mg extended release. Efficacy end points included change from baseline at week 12 in mean daily number of micturitions, UUI episodes, and urgency episodes. Safety was assessed through adverse events (AEs).. Of the patients included in the analysis, 1286 (84.9%) were women (vibegron, n = 463; placebo, n = 459; tolterodine, n = 364). At week 12, women receiving vibegron showed significant reductions (95% confidence intervals of least squares mean differences does not include 0) from baseline versus placebo in mean daily micturitions, UUI episodes, and urgency episodes, with least squares mean differences (95% confidence intervals) of -0.5 (-0.8 to -0.2), -0.7 (-1.0 to -0.4), and -0.8 (-1.3 to -0.4), respectively. Treatment-emergent AE incidence was similar with vibegron (39%) and placebo (35%); the most common AE with incidence higher with vibegron (4.3%) than placebo (2.6%) was headache.. In this subgroup analysis, women receiving vibegron showed significant reductions in key efficacy end points versus placebo and favorable safety profile, consistent with the overall results from EMPOWUR, suggesting that vibegron is efficacious and safe for the treatment of OAB in this patient population.

Topics: Adult; Female; Humans; Male; Pyrimidinones; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge

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

To characterize the blood pressure (BP) profile of the new β3-adrenergic receptor agonist, vibegron, in patients with overactive bladder.. Patients were randomized to once-daily vibegron 75 mg or placebo for 28 days and underwent ambulatory BP monitoring. The primary endpoint was change from baseline (CFB) to day 28 in mean daytime ambulatory systolic BP (SBP). Secondary endpoints were CFB in mean 24-h SBP and in mean daytime and mean 24-h ambulatory diastolic BP (DBP) and heart rate (HR). Safety was assessed through adverse event reporting.. Of 214 patients randomized, 96 receiving vibegron and 101 receiving placebo had evaluable baseline and day 28 measurements. Overall, 39.6 and 30.7% of patients receiving vibegron and placebo, respectively, had preexisting hypertension. The least squares mean difference (LSMD; 90% confidence interval) between vibegron and placebo in CFB in mean daytime SBP was 0.8 (-0.9, 2.5) mmHg. LSMD in CFB in mean daytime DBP and HR was 0.0 mmHg and 0.9 bpm, respectively. No significant differences between treatments were seen in CFB in mean 24-h SBP (LSMD, 0.6 mmHg), DBP (-0.2 mmHg) or HR (1.0 bpm). The most common treatment-emergent adverse event was hypertension, with rates comparable between groups [vibegron: n = 5 (4.7%); placebo: n = 4 (3.7%)]. One patient receiving vibegron took a prohibited medication (phentermine) known to increase BP.. Once-daily vibegron had no statistically significant or clinically relevant effects on BP or HR.

Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Humans; Hypertension; Pyrimidinones; Pyrrolidines; Treatment Outcome; Urinary Bladder, Overactive

Reductions in bothersome symptoms of overactive bladder (OAB) demonstrate improvement in clinical trials, but patient perception of meaningfulness of such improvement is lacking. In the 12-week phase 3 EMPOWUR trial, vibegron significantly reduced average daily number of micturitions, urgency episodes, and urge urinary incontinence (UUI) episodes vs placebo (P < 0.01 each). This analysis assessed meaningfulness of reductions in clinical endpoints observed in EMPOWUR using patient perception of improvement.. An anchor-based approach using Patient Global Impression of Change (PGI-C) applied to phase 2 data allowed predefining phase 3 responder definitions. To confirm in phase 3, median change from baseline at week 12 in average daily number of micturitions, urgency episodes, and UUI episodes was generated for each PGI-C category and pooled across treatments. Based on predefined meaningful responder definitions, percentages of patients achieving ≥ 15% reduction in micturitions (post hoc), ≥ 50% reduction in urgency episodes (predefined), and ≥ 75% (predefined) and ≥ 90% (post hoc) reduction in UUI episodes were determined for patients receiving vibegron or placebo.. Across treatments, for micturitions, urgency episodes, and UUI episodes, median change from baseline to week 12 increased with greater subjective improvement based on PGI-C scores, and median reductions pooled across treatment groups were higher than the responder definitions that patients perceived as improved. Significantly more patients receiving vibegron vs placebo achieved ≥ 15% reduction in micturitions (56.3% vs 44.6%, respectively), ≥ 50% reduction in urgency episodes (39.5% vs 32.8%), ≥ 75% reduction in UUI episodes (49.3% vs 32.8%), and ≥ 90% reduction in UUI episodes (35.2% vs 23.5%) at week 12 (P < 0.05 each).. Significantly more patients treated with vibegron vs placebo in EMPOWUR achieved meaningful reductions in micturitions, urgency episodes, and UUI episodes that were associated with patient-perceived improvement. Results of these analyses support the meaningfulness of reductions in clinical endpoints observed in the 12-week EMPOWUR trial.. ClinicalTrials.gov identifier, NCT03492281.

Topics: Double-Blind Method; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder (OAB) is characterized by urgency and frequency with (OAB wet) or without (OAB dry) urge urinary incontinence (UUI). In the phase 3 EMPOWUR trial, vibegron-a selective. Patients were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, for 12 weeks. Baseline criteria for OAB dry included an average of ≥8 micturitions, ≥3 urgency episodes, and <1 UUI episode per diary day and for OAB wet included an average of ≥8 micturitions and ≥1 UUI episode per diary day. Change from baseline in mean daily number of urgency episodes and micturitions was assessed in both populations.. Of the 1463 patients included in the full analysis set, 336 (23%) had OAB dry (vibegron,. In this subgroup analysis from the EMPOWUR trial, vibegron was associated with significant reductions compared with placebo in urgency episodes and micturitions in both the OAB dry and wet populations, suggesting that vibegron is similarly efficacious for these endpoints in patients with and without UUI. This trial is registered with NCT03492281.

Topics: Double-Blind Method; Humans; Pyrimidinones; Pyrrolidines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge

Oral pharmacotherapy for overactive bladder, a condition that increases with age, includes anticholinergics and β

Topics: Aged; Humans; Pyrimidinones; Pyrrolidines; Tablets; Urinary Bladder, Overactive

Quality of life (QOL) can be significantly impacted by symptoms of overactive bladder (OAB). Vibegron is a highly selective β. Patients were randomly assigned 5:5:4 to receive vibegron 75 mg, placebo or tolterodine 4 mg extended release, respectively, for 12 weeks. Patients completed the OAB questionnaire (OAB-q) at baseline and at week 12 and the patient global impression (PGI) scales for severity, control, frequency and leakage at baseline and at weeks 4, 8 and 12. Change from baseline at week 12 and responder rates (OAB-q: patients achieving a ≥10-point improvement; PGI: patients reporting best possible response) were assessed. Vibegron was compared with placebo, and no comparisons were made between vibegron and tolterodine.. Of the 1518 patients randomised, 1463 (placebo, n = 520; vibegron, n = 526; tolterodine, n = 417) had evaluable data for efficacy measures and were included in the analysis. Mean baseline OAB-q and PGI scores were comparable among treatment groups. At week 12, patients receiving vibegron had greater improvements from baseline in OAB-q subscores of coping, concern, sleep, health-related QOL total and symptom bother (P < .01 each) compared with patients receiving placebo; a greater proportion of patients receiving vibegron vs placebo were responders in the OAB-q coping (P < .05) and symptom bother scores (P < .0001). Compared with placebo, a greater proportion of patients who received vibegron achieved the best response on all PGI end-points at week 12 (P < .05 each) and were classified as responders (P < .05 each).. In the 12-week EMPOWUR trial, treatment with vibegron was associated with significantly greater and clinically meaningful improvement in OAB-q and PGI scores compared with placebo, consistent with improvements in OAB symptoms.. ClinicalTrials.gov identifier number NCT03492281.

Topics: Double-Blind Method; Humans; Muscarinic Antagonists; Patient Reported Outcome Measures; Pyrimidinones; Pyrrolidines; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

The long-term safety, tolerability and efficacy of vibegron in adults with overactive bladder were evaluated in the 40-week phase 3 EMPOWUR extension study.. Patients who completed 12 weeks of once-daily vibegron 75 mg or tolterodine 4 mg extended release in EMPOWUR continued double-blind treatment; patients who completed 12 weeks of placebo were randomly assigned 1:1 to receive double-blind vibegron or tolterodine. The primary outcome was safety, measured by incidence of adverse events. Secondary outcomes included change from baseline at week 52 in average daily number of micturitions and urgency episodes (all patients), and urge and total urinary incontinence episodes (patients with overactive bladder wet) based on 7-day diary data.. Of 506 patients randomized 505 received ≥1 dose of medication, and 430 (85%) completed the study. A total of 12 patients (2.4%) discontinued owing to adverse events. The most common adverse events with vibegron/tolterodine (>5% in either group) were hypertension (8.8%/8.6%), urinary tract infection (6.6%/7.3%), headache (5.5%/3.9%), nasopharyngitis (4.8%/5.2%) and dry mouth (1.8%/5.2%). Improvements in efficacy end points were maintained for patients receiving vibegron for 52 weeks; least squares mean change from baseline to week 52 in micturitions was ‒2.4 for vibegron vs ‒2.0 for tolterodine; in urge urinary incontinence episodes ‒2.2 vs ‒1.7 (p <0.05); in urgency episodes ‒3.4 vs ‒3.2; and in total incontinence episodes ‒2.5 vs ‒1.9 (p <0.05). Among patients with overactive bladder wet 61.0% receiving vibegron experienced ≥75% reduction in urge urinary incontinence episodes after 52 weeks of treatment vs 54.4% with tolterodine, while 40.8% vs 34.2% experienced a 100% reduction.. Vibegron demonstrated favorable long-term safety, tolerability and efficacy in patients with overactive bladder, consistent with results of the 12-week study.

Topics: Aged; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder (OAB) is common among older adults. The efficacy and safety of vibegron for the treatment of OAB were demonstrated in the international, phase III EMPOWUR trial. This subpopulation analysis from EMPOWUR assessed the efficacy and safety of vibegron in patients aged ≥ 65 and ≥ 75 years.. In EMPOWUR, patients with OAB were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, once daily for 12 weeks. Coprimary efficacy endpoints were change from baseline at week 12 in average daily number of micturitions and urge urinary incontinence (UUI) episodes; a key secondary efficacy endpoint was change from baseline at week 12 in average daily number of urgency episodes. Safety was assessed through adverse events (AEs). Efficacy analyses compared vibegron with placebo; no efficacy comparisons were made between vibegron and tolterodine.. Of the 1463 patients with evaluable efficacy data, 628 patients were aged ≥ 65 years, and 179 were aged ≥ 75 years. After 12 weeks, patients treated with once-daily vibegron 75 mg in both age subgroups showed significant improvements from baseline versus placebo in all three symptoms of OAB: daily micturitions (≥ 65 years, P < 0.0001; ≥75 years, P < 0.05), UUI episodes (≥ 65 years, P < 0.001; ≥ 75 years, P < 0.0001), and urgency episodes (≥ 65 years, P < 0.01; ≥ 75 years, P < 0.01). Significant reductions from baseline versus placebo in daily micturitions, UUI episodes, and urgency episodes were observed beginning at week 2 for patients aged ≥ 65 years treated with vibegron. In patients aged ≥ 65 years, 50.0% of those receiving vibegron versus 29.8% receiving placebo experienced a ≥ 75% reduction in UUI episodes at week 12 (P < 0.0001). Rates of cardiovascular-associated AEs were low for patients receiving vibegron (<2% of patients in either age subgroup) and similar to rates in patients receiving placebo. In patients aged ≥ 65 years, hypertension was reported by 1.2%, 3.1%, and 2.9% of patients receiving vibegron, placebo, and tolterodine, respectively; in patients aged ≥ 75 years, hypertension was reported by 1.3%, 3.3%, and 2.1%, respectively.. In this subpopulation analysis of patients with OAB aged ≥ 65 and ≥ 75 years from the EMPOWUR study, once-daily vibegron 75 mg showed rapid onset and robust efficacy versus placebo and was generally safe and well tolerated, consistent with results from the overall population.. ClinicalTrials.gov identifier NCT03492281; registered April 10, 2018.

Topics: Aged; Double-Blind Method; Humans; Pyrimidinones; Pyrrolidines; Treatment Outcome; Urinary Bladder, Overactive

To investigate the efficacy and safety of vibegron add-on therapy in men with persistent storage symptoms receiving α-1 blockers or PDE5 inhibitor for benign prostatic hyperplasia and then determine the independent factors affecting the efficacy of vibegron.. Vibegron 50 mg was administered for 12 weeks to 42 patients (72.0 ± 8.2 years) with persistent storage symptoms who had taken α-1 blockers (22 patients) or PDE5 inhibitor (20 patients). The primary endpoint was change in the overactive Bladder (OAB) Symptom Score from baseline to end of treatment. The secondary endpoints were changes in each question of several questionnaires, maximum flow rate and residual urine volume. Finally, independent factors affecting the efficacy of vibegron were investigated.. Total OAB Symptom Score was significantly decreased (6.21 ± 3.12 vs 4.38 ± 2.46; P < .001). Although each score of several questionnaires, especially for storage symptoms, improved significantly, no significant improvement was found in stress incontinence, straining, bladder pain and urethral pain in the Core Lower Urinary Tract Symptom score. Maximum flow rate and residual urine volume did not change, and no patient discontinued vibegron because of adverse events. Multiple regression analysis showed that OAB Symptom Score, Core Lower Urinary Tract Symptom score, prostate volume and monotherapy with α-1 blocker were independent factors affecting the efficacy of vibegron.. Add-on therapy of vibegron to monotherapy with α-1 blockers or PDE5 inhibitor for patients with benign prostatic hyperplasia and persistent storage symptoms was effective and safe.

Topics: Adrenergic alpha-Antagonists; Aged; Drug Therapy, Combination; Humans; Male; Phosphodiesterase 5 Inhibitors; Prospective Studies; Prostatic Hyperplasia; Pyrimidinones; Pyrrolidines; Urinary Bladder, Overactive; Urodynamics

To examine the safety and efficacy of vibegron, a new β3-adrenoceptor agonist, in patients aged ≥65 years, with a focus on the effects on cardiovascular system and overactive bladder (OAB) symptoms.. A post-hoc subgroup analysis was performed of a randomized, placebo-controlled, double-blind comparative phase 3 study of vibegron, including those assigned to receive either vibegron 50 mg (V50), vibegron 100 mg (V100), or placebo for 12 weeks. Subjects were stratified into two subgroups based on age: a <65-year subgroup and a ≥65-year subgroup. Safety (changes in systolic and diastolic blood pressure, pulse rate, and residual urine volume) and efficacy (changes in the numbers of micturitions, urgency episodes, urgency urinary incontinence [UUI] episodes, and the voided volume/micturition) were assessed in the subgroups treated with vibegron vs. placebo.. There were no significant differences in the cardiovascular outcomes (blood pressure and pulse rate), nor in the changes in residual urine volume, between the V50/100 and placebo groups in the <65-year or ≥65-year subgroup after 12-week treatment. Adverse events were slightly increased in the ≥65-year subgroup. In the efficacy analysis, V50/100 demonstrated similar efficacy in the <65-year and ≥65-year subgroups; an increasing trend in the voided volume/micturition was observed in subjects aged ≥65 years compared to subjects aged <65 years.. Vibegron was suggested to be similarly effective in patients ≥65 and <65 years and to have minimal influence on cardiovascular parameters.

Topics: Adrenergic beta-3 Receptor Agonists; Aged; Cardiovascular System; Double-Blind Method; Humans; Middle Aged; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Receptors, Adrenergic; Treatment Outcome; Urinary Bladder, Overactive

To evaluate the efficacy of a novel and selective β3-adrenoreceptor agonist vibegron on urgency urinary incontinence (UUI) in patients with overactive bladder (OAB).. A post hoc analysis was performed in patients with UUI (>0 episodes/day) who were assigned to receive vibegron or placebo in a vibegron phase 3 study. Patients were subclassified into mild/moderate (>0 to <3 UUI episodes/day) or severe UUI (≥3 UUI episodes/day) subgroup. Changes from baseline in number of UUI episodes/day, in number of urgency episodes/day, and in voided volume/micturition were compared between the groups. The percentage of patients who became UUI-free ('diary-dry' rate) and the response rate (percentage of patients with scores 1 [feeling much better] or 2 [feeling better] assessed by the Patient Global Impression scale [PGI]) were evaluated.. Changes in numbers of UUI episodes at week 12 in the vibegron 50 mg, vibegron 100 mg and placebo groups, respectively, were -1.35, -1.47 and -1.08 in all patients, -1.04, -1.13 and -0.89 in the mild/moderate UUI subgroup, and -2.95, -3.28 and -2.10 in the severe UUI subgroup. The changes were significant in the vibegron 50 and 100 mg groups vs placebo regardless of symptom severity. Change in number of urgency episodes/day was significant in the vibegron 100 mg group vs placebo in all patients and in both severity subgroups. In the vibegron 50 mg group, a significant change vs placebo was observed in all patients and in the mild/moderate UUI subgroup. Change in voided volume/micturition was significantly greater in the vibegron 50 and 100 mg groups vs placebo in all patients, as well as in the both severity subgroups. Diary-dry rates in the vibegron 50 and 100 mg groups were significantly greater vs placebo in all patients and in the mild/moderate UUI subgroup. In the severe UUI subgroup, however, a significant difference was observed only in the vibegron 50 mg group. Response rates assessed by the PGI were significantly higher in the vibegron groups vs placebo in all patients and in the both severity subgroups. Vibegron administration, OAB duration ≤37 months, mean number of micturitions/day at baseline <12.0 and mean number of UUI episodes/day at baseline <3.0 were identified as factors significantly associated with normalization of UUI.. Vibegron, a novel β3-adrenoreceptor agonist, significantly reduced the number of UUI episodes/day and significantly increased the voided volume/micturition in patients with OAB including those with severe UUI, with the response rate exceeding 50%. These results suggest that vibegron can be an effective therapeutic option for OAB patients with UUI.

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

We assessed efficacy, safety and tolerability of vibegron, a novel, potent, highly selective β. Adult patients with overactive bladder with 8.0 or more micturitions per day were randomized 5:5:4 to 75 mg vibegron, placebo or extended-release 4 mg extended-release tolterodine. Up to 25% of patients could have dry overactive bladder (less than 1.0 urge incontinence episode per day). Patients completed 7-day voiding diaries at baseline and weeks 2, 4, 8 and 12.. Of 1,518 randomized patients 90.4% completed the trial. At 12 weeks micturitions decreased by an adjusted mean of 1.8 episodes per day for vibegron vs 1.3 for placebo (p <0.001, co-primary end point) and 1.6 for tolterodine. Among incontinent patients urge incontinence episodes decreased by an adjusted mean 2.0 episodes per day for vibegron vs 1.4 for placebo (p <0.0001, co-primary end point) and 1.8 for tolterodine. Moreover, vibegron was statistically significantly superior to placebo for key secondary measures of number of urgency episodes, volume per micturition and proportion of incontinent patients with a 75% or greater reduction in urge incontinence episodes (all p <0.01). Among vibegron treated patients 1.7% discontinued treatment because of adverse events vs 1.1% for placebo and 3.3% for tolterodine. Incidence of hypertension was 1.7% for vibegron and for placebo.. Once daily 75 mg vibegron provided statistically significant reductions in micturitions, urgency episodes and urge incontinence, and increased the volume per micturition. Treatment was well tolerated with a favorable safety profile.

Topics: Adrenergic beta-3 Receptor Agonists; Adult; Aged; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Internationality; Male; Middle Aged; Pyrimidinones; Pyrrolidines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urological Agents

To investigate the efficacy of vibegron on nocturia in patients with overactive bladder.. Among the Japanese overactive bladder patients enrolled in the placebo-controlled, multicenter, randomized, double-blind phase 3 study of vibegron, a total of 669 patients with nocturia (≥1 nocturnal void) were included. Changes from baseline in micturition parameters were compared for vibegron treatment (50 and 100 mg/day) versus placebo. Correlations of hours of undisturbed sleep with the frequency of nocturnal voiding and the volume of the first nocturnal voiding were examined. Demographics and baseline characteristics contributing to reduction in the frequency of nocturnal voiding were also analyzed.. At week 12, the frequency of nocturnal voiding was reduced from baseline by 0.74 and 0.78, respectively, for the vibegron 50 and 100 mg groups; the reductions were significant when compared with the placebo group (P < 0.05 and P < 0.001, respectively). The mean volume of nocturnal voids and the volume of the first nocturnal voiding were significantly greater in the vibegron groups than in the placebo group. The vibegron groups showed significant correlations of hours of undisturbed sleep with the changes in the frequency of nocturnal voiding and in the volume of the first nocturnal voiding. Vibegron treatment, no previous treatment with anticholinergics, ≥12 voids per day and hours of undisturbed sleep <180 min significantly contributed to a reduction in the frequency of nocturnal voiding.. Vibegron is a useful therapeutic option for improving nocturia in patients with overactive bladder.

Topics: Adrenergic beta-3 Receptor Agonists; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Nocturia; Placebos; Pyrimidinones; Pyrrolidines; Quality of Life; Treatment Outcome; Urinary Bladder, Overactive

Antimuscarinics have shown modest efficacy with unwanted side effects in patients with overactive bladder (OAB). Efficacy of vibegron, a new β3-adrenergic receptor agonist, for OAB is unknown.. To evaluate the efficacy of once-daily oral vibegron in OAB patients (primary), and its safety, tolerability, and efficacy when administered alone or concomitantly with tolterodine (secondary).. International, phase IIb, randomized, double-blind, placebo- and active comparator-controlled, two-part superiority trial (2011-2013) in OAB-wet or OAB-dry patients aged 18-75 yr (NCT01314872).. Part 1: once-daily oral vibegron monotherapy (3 [V3], 15 [V15], 50 [V50], or 100 [V100] mg), tolterodine extended release 4mg (TER4), or placebo for 8 wk, or combination V50/TER4 for 4 wk and then V50 for 4 wk; part 2: V100/TER4, V100, TER4, or placebo for 4 wk.. Average daily micturitions at week 8 of part 1 (primary); urge incontinence episodes, total incontinence episodes, and urgency episodes (secondary).. Overall, 1395 patients were randomized. From baseline to week 8, V50 and V100 significantly decreased average daily micturitions (least square mean difference [95% confidence interval], -0.64 [-1.11, -0.18]; p=0.007 and -0.91 [-1.37, -0.44]; p<0.001, respectively) and the number of urge incontinence episodes (-0.72 [-1.11, -0.33] and -0.71 [-1.10, -0.32], respectively; both p<0.001) versus placebo. All vibegron doses were well tolerated. The incidence of dry mouth was higher with TER4 than with vibegron monotherapy. Results are limited by the relatively short treatment duration.. Once-daily V50 and V100 improved OAB symptoms; vibegron was well tolerated as monotherapy and concomitantly with tolterodine. Further development is warranted.. Antimuscarinics, commonly used to treat overactive bladder, produce modest efficacy and unwanted side effects. In this study, a different type of drug (vibegron) was efficacious and safe, alone or with an antimuscarinic (tolterodine).

Topics: Administration, Oral; Adolescent; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Recovery of Function; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urination; Young Adult

Vibegron is a novel, potent, and selective β. To evaluate the efficacy and safety of vibegron versus placebo in Japanese OAB patients.. Patients with OAB entered a 2-wk placebo run-in phase. Once eligibility (≥8 micturition/d and either ≥1 urgency episodes/d or ≥1 urgency incontinence episodes/d) was confirmed, patients entered a 12-wk double-blind treatment phase. The anticholinergic imidafenacin was used as an active reference.. A total of 1232 patients were randomly assigned to one of the four 12-wk treatment groups: vibegron (50mg or 100mg once daily), placebo, or imidafenacin (0.1mg twice daily).. The primary endpoint was change in the mean number of micturitions/d at wk 12 from baseline. The secondary endpoints were changes from baselines in OAB symptom variables (daily episodes of urgency, urgency incontinence, incontinence, and nocturia, and voided volume/micturition). Quality of life (QoL) and safety were assessed. A constrained longitudinal data analysis model was used for analysis of efficacy.. Patients taking vibegron 50mg and 100mg orally for 12 wk had significant improvements over the placebo in the primary and secondary endpoints. The proportions of patients with normalization of micturition, resolution of urgency, urgency incontinence, and incontinence were significantly greater than placebo. Vibegron significantly improved QoL, with high patient satisfaction. Incidences of drug-related adverse events with vibegron 50mg and 100mg were 7.6%, 5.4%, similar to placebo (5.1%), and less than imidafenacin (10.3%). Treatment was for just 12 wk and a long-term study is needed.. The 12-wk treatment with vibegron is effective and well tolerated in patients with OAB.. This randomized study demonstrated that vibegron is clinically useful for treatment of patients with OAB. Trial registration ​JapicCTI-152936. http://www.clinicaltrials.jp/user/cteDetail.jsp.

Topics: Adrenergic beta-3 Receptor Agonists; Adult; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Imidazoles; Japan; Male; Middle Aged; Pyrimidinones; Pyrrolidines; Quality of Life; Reference Values; Risk Assessment; Severity of Illness Index; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics

To evaluate the long-term safety and efficacy of vibegron 50 mg and 100 mg, a novel β. This was a 1-year, multicenter, open-label, non-controlled study. After a 1-week observation phase, patients were treated with vibegron for 52 weeks. When the efficacy was insufficient after an 8-week treatment with 50 mg, the dose was increased to 100 mg and maintained for an additional 44 weeks.. Among a total of 169 patients receiving one or more doses of vibegron, 118 (69.8%) received vibegron 50 mg for 52 weeks, and the dose was increased to 100 mg in 51 (30.2%) patients. The incidence of drug-related adverse events was 18.1% (21/116) in the vibegron 50 mg group and 11.8% (6/51) in the vibegron 100 mg group. Most frequent drug-related adverse events were dry mouth (3.0%), residual urine volume increased (3.0%), constipation (2.4%) and cystitis (1.8%). Statistically significant changes in overactive bladder symptom variables (daily means of micturitions, urgency episodes, urgency incontinence episodes, incontinence episodes and night-time frequency) from baseline were observed at week 4 and maintained until week 52. The condition of patients who did not respond well to vibegron 50 mg was much improved by increasing the dose to 100 mg. Vibegron improved the quality of life, and the proportion of patients' satisfaction after the treatment with vibegron was high.. Long-term (52-week) treatment with vibegron is safe, well-tolerated and effective in patients with overactive bladder.

Topics: Adrenergic beta-3 Receptor Agonists; Aged; Constipation; Cystitis; Dose-Response Relationship, Drug; Female; Humans; Incidence; Japan; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Pyrimidinones; Pyrrolidines; Quality of Life; Treatment Outcome; Urinary Bladder, Overactive; Xerostomia

To evaluate the efficacy and safety of the phosphodiesterase type 5 inhibitor, UK-369,003 modified release (MR), for the treatment of storage lower urinary tract symptoms (LUTS) in men with and without erectile dysfunction (ED).. This was a multicentre, double-blind, placebo-controlled, parallel-group study conducted across 50 centres in North and South America, Europe and Australia. In all, 310 men aged ≥ 18 years with a clinical diagnosis of overactive bladder (OAB; voiding frequency ≥ 8 times/24 h, urgency episode frequency once or more per 24 h and a mean voided volume of <300 mL) and maximum urinary flow rate of >5 mL/s in a voided volume of >150 mL were stratified into two groups (with or without ED) and randomized to one of five treatment groups (10, 25, 50 or 100 mg UK-369,003; or placebo once a day) for 12 weeks. The primary study endpoints were those derived from the bladder diary that recorded the number of voluntary urinary voids, volume of urine per void, leaks and urgency episodes over a 72-h period, before baseline and again at 2, 4 and 12 weeks. Secondary efficacy measures included the International Prostate Symptom Score (total and storage and voiding subscores), International Index of Erectile Function-Erectile Function domain (IIEF-EF), questions 5 and 6 of the Quality of Erection Questionnaire (QEQ), the Overactive Bladder Questionnaire Short Form, the Patient Perception of Bladder Condition, the International Consultation on Incontinence Questionnaire-Male LUTS, and the patient-reported treatment impact questionnaire.. Overall, there were no clinically relevant treatment differences in voiding frequency, mean voided volume, urgency episode frequency, or nocturia frequency for any dose of UK-369,003 MR compared with placebo. In the subset of patients with ED there were improvements in the IIEF-EF and QEQ scores in all UK-369,003 treatment groups compared with placebo.. These data provide no evidence of efficacy for UK-369,003 in the treatment of storage LUTS in men (based on classic OAB eligibility criteria). However, although the endpoints on these classic OAB efficacy variables were negative, there is evidence to suggest a greater preference, satisfaction and willingness to use UK-369,003 again for all treatment groups compared with placebo.

Topics: Epidemiologic Methods; Erectile Dysfunction; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Prostatism; Pyrimidinones; Quality of Life; Sulfonamides; Treatment Outcome; Urinary Bladder, Overactive

Sparse published reports exist nowadays on vibegron and pediatric overactive bladder, so its usefulness of this agent remains unclear. The purpose of this study was to clarify the effectiveness of vibegron for pediatric cases of daytime urinary incontinence (DUI), including refractory cases.. Participants comprised 57 patients treated with vibegron for DUI from March 2019 to April 2022. To investigate treatment outcomes and risk factors for pediatric patients with refractory DUI, the following factors were evaluated: age at initiatial administration; frequency of DUI; duration of vibegron treatment; presence of neurodevelopmental disorders (NDDs); presence of constipation; and anticholinergic medications before and after initiation of treatment.. Patients included 38 boys and 19 girls with a median age at initial administration of 111 months (range: 64-202 months) and a median administration term of 6 months (range: 1-33 months). With treatment for 6 months, the response rate (complete response + partial response) was 68.3%. A total of 24 cases with NDD showed a 72.0% response rate at 6 months. As for the relationship between anticholinergic agents and vibegron, 15 cases were treated with vibegron as the first choice without anticholinergics (First-choice cases), and 33 cases were treated with vibegron alone after switching from anticholinergics (Switch cases). Vibegron was used in combination with anticholinergic agents in 9 cases (Add-on cases). Response rates at 6 months were 85.0% in First-choice cases, 66.3% in Switch cases, and 40.7% in Add-on cases. Univariate analyses failed to identify any significant risk factors for refractory cases.. Vibegron was effective in pediatric cases of DUI, with efficacy demonstrated within a short time in many cases. Vibegron is expected to play a significant role in the treatment of DUI in pediatric cases.

Topics: Child; Cholinergic Antagonists; Diurnal Enuresis; Female; Humans; Male; Pyrimidinones; Urinary Bladder, Overactive

To evaluate the efficacy and safety of vibegron in patients with overactive bladder (OAB) in real-world clinical practice in Japan.. This multicenter, prospective, non-controlled study consecutively enrolled patients with OAB determined by an OAB symptom score (OABSS) of three points or more and a question 3 (urgency) score of two points or more. A total of 212 patients from 43 institutions were recruited from January 2019 through March 2020. Vibegron, 50 mg, was administrated daily for 8 weeks as first-line monotherapy (first-line group, FL), monotherapy switching from antimuscarinics (post-antimuscarinic group, PA) or mirabegron (post-mirabegron group, PM) and combination therapy with antimuscarinics (add-on group). The OABSS was collected at baseline and every 2 weeks. Adverse events were recorded at every visit.. Of the 212 patients registered, 188 (male 76, female 112) were eligible for analysis (124 in the FL group, 27 in PA, 29 in PM, and eight in the add-on group). The add-on group was excluded from further analysis due to its small number. The OABSS (mean ± SD) showed significant improvement in all groups (FL; 8.8 ± 2.5, 3.8 ± 2.8, PM; 9.4 ± 2.2, 4.5 ± 4.0, PM; 8.9 ± 2.5, 4.7 ± 3.3 at 0 and 8 weeks, respectively). The overall incidence of adverse events was 25%. No grade 3 or higher adverse events were observed.. In the real-world clinical setting, vibegron is effective and well-tolerated by OAB patients, including those switching therapy from antimuscarinics and mirabegron.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Female; Humans; Japan; Male; Muscarinic Antagonists; Prospective Studies; Pyrimidinones; Pyrrolidines; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

A Retrospective study.. To investigate the effects of vibegron on urodynamic parameters of individuals with spinal cord injury (SCI).. The National Hospital Organization, Murayama Medical Center, Japan.. Vibegron administration increased the maximum cystometric capacity (MCC) (median, from 185.0 to 340.0 mL, P = 0.001), bladder compliance (median, from 8.3 to 20.0 mL/cmH. Vibegron therapy improved the bladder capacity and bladder compliance of individuals with NLUTD and SCI.

Topics: Humans; Pyrimidinones; Pyrrolidines; Retrospective Studies; Spinal Cord Injuries; Urinary Bladder; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

Overactive bladder (OAB) is associated with considerable clinical and economic burden. Treatment of patients with OAB using anticholinergics is limited by tolerability issues and increased anticholinergic burden, which is associated with increased risk of dementia and falls/fractures. This analysis assessed the budget impact of introducing the β. A budget impact model (BIM) with a 5-year time horizon was developed using a top-down, prevalence-based approach and projected market shares for 1-million-member US commercial and Medicare plans. The BIM included vibegron, mirabegron, and anticholinergics, incorporating changes in clinical outcomes (efficacy, drug-drug interactions, anticholinergic burden (ACB), OAB-related comorbidities, and adverse events (AEs)). Costs per member per month (PMPM) and per treated member per month (PTMPM) were determined. One-way sensitivity analyses quantified the impact of changes in key variables.. The introduction of vibegron was associated with a modest increase in PMPM cost over 5 years of $0.12 (range for years 1‒5, $0.01‒$0.26) for commercial payors and $0.24 ($0.01‒$0.52) for Medicare (PTMPM cost: $2.70 ($0.17‒$4.85) and $3.15 ($0.19‒$5.82), respectively). Costs were partially offset by savings related to decreased third-line treatment use, yearly decreases in AE and comorbidity incidence, reduced drug-drug interactions, and reduced ACB associated with vibegron introduction. PMPM costs were most sensitive to vibegron market share assumptions, OAB prevalence, and vibegron persistence at 1 month for private payors and Medicare and additionally vibegron persistence at 12 months for Medicare.. Vibegron may address unmet needs in treating OAB and is a useful addition to health plans while minimizing risks of anticholinergic AEs, ACB, and drug-drug interactions, which may partially offset increased pharmacy costs.. Adults with overactive bladder (OAB) experience frequent and sudden urges to urinate. OAB affects more than 100 million men and women in the USA. In 2020, the projected cost of OAB was $82.6 billion. One of the standard treatments for OAB includes a class of drugs called anticholinergics. Anticholinergic drugs can cause side effects such as dry mouth and constipation. Over time, taking a lot of anticholinergic drugs may lead to increased risk of cognitive impairment or dementia. Vibegron is from a different class of drug for the treatment of OAB known as β

Topics: Adrenergic Agonists; Aged; Cholinergic Antagonists; Humans; Medicare; Pyrimidinones; Pyrrolidines; United States; Urinary Bladder, Overactive

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

To examine the effects of vibegron, a selective β. Muscarinic receptors in the rat bladder and other tissues were examined by a radioligand binding assay using [N-methyl-. Vibegron (0.1-100 μmol/L) inhibited specific [N-methyl-. This is the first study to suggest that vibegron binds to muscarinic receptors in the rat bladder and other tissues, with a potentially higher affinity for the M

Topics: Animals; Humans; Pyrimidinones; Pyrrolidines; Rats; Receptors, Muscarinic; Urinary Bladder; Urinary Bladder, Overactive

Myelomeningocele, which causes a neurogenic bladder, is usually treated with anticholinergics in children with neurogenic detrusor overactivity (NDO); however, anticholinergics cause side effects such as dry mouth, constipation, attention deficit, and inadequate reduction in detrusor leak point pressure. Vibegron, a novel selective beta-3 adrenoreceptor agonist, is a well-established alternative to anticholinergics in adults with an overactive bladder. It remains unknown whether this agent can be used for pediatric patients. We report the case of a girl with anticholinergic-resistant NDO due to tethered cord syndrome after myelomeningocele repair, who was treated with vibegron.. A 4-year-old Filipino girl had increased frequency of daytime urinary incontinence and foul-smelling urine since the age of 3. Clinical examination revealed constipation, and urinalysis revealed bacteriuria. Voiding cystourethrography revealed an enlarged and trabeculated bladder without vesicoureteral reflux. On the urodynamic study (UDS), she was found to have detrusor overactivity (DO) and low bladder compliance. She could not void and was diagnosed with overflow incontinence. Clean intermittent catheterization (CIC) and orally administered propiverine (0.8 mg/kg/day) were initiated, and urinary incontinence was resolved. She underwent a UDS annually; the UDS at 6 years of age still revealed DO and low bladder compliance in spite of receiving propiverine. The treatment was switched from propiverine to vibegron (1.4 mg/kg/day). On the UDS after a 5-week treatment schedule of vibegron, the DO disappeared and the bladder compliance improved. CIC and orally administered vibegron have been continued for 7 months so far, and she has had no urinary tract infection with no drug-related adverse events.. Vibegron was effective and well tolerated in the treatment of a pediatric patient with NDO. Vibegron improved the urodynamic parameters for anticholinergic-resistant neurogenic bladder. This agent can be a beneficial and preferable alternative therapeutic agent to anticholinergics in patients with anticholinergic-resistant NDO.

Topics: Adult; Child; Child, Preschool; Cholinergic Antagonists; Female; Humans; Pyrimidinones; Pyrrolidines; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics

Topics: Adrenergic beta-3 Receptor Agonists; Humans; Pyrimidinones; Pyrrolidines; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive

Topics: Algorithms; Humans; Meat; Pyrimidinones; Pyrrolidines; Urinary Bladder, Overactive

Overactive bladder (OAB) is an extremely common condition in adults of both sexes. It is characterized by an urgent need to micturate often accompanied by incontinence. The condition may also increase the number of micturitions in a 24-hour period as well as nocturia. The syndrome is not due to a urinary infection or other obvious pathology. In terms of drug treatment of OAB, there are two main approaches. One is the use of anticholinergic drugs that reduce the effect of the parasympathetic nervous system on the bladder. The other involves the use of drugs that are agonists at β

Topics: Acetanilides; Adrenergic Agonists; Adrenergic beta-3 Receptor Agonists; Adult; Female; Humans; Male; Pyrimidinones; Pyrrolidines; Treatment Outcome; Urinary Bladder, Overactive

Topics: Double-Blind Method; Humans; Pyrimidinones; Pyrrolidines; Urinary Bladder, Overactive

Topics: Double-Blind Method; Humans; Pyrimidinones; Pyrrolidines; Urinary Bladder, Overactive

Topics: Humans; Pyrimidinones; Pyrrolidines; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive; Urodynamics

Topics: Adrenergic Agonists; Double-Blind Method; Humans; Pyrimidinones; Pyrrolidines; Tolterodine Tartrate; Urinary Bladder, Overactive

Topics: Adrenergic beta-3 Receptor Agonists; Double-Blind Method; Humans; Nocturia; Pyrimidinones; Pyrrolidines; Urinary Bladder, Overactive

Topics: Adrenergic beta-3 Receptor Agonists; Double-Blind Method; Humans; Pyrimidinones; Pyrrolidines; Urinary Bladder, Overactive

Topics: Adrenergic beta-3 Receptor Agonists; Humans; Prospective Studies; Pyrimidinones; Pyrrolidines; Urinary Bladder, Overactive

Topics: Adrenergic beta-3 Receptor Agonists; Humans; Prospective Studies; Pyrimidinones; Pyrrolidines; Urinary Bladder, Overactive

Vibegron is a selective beta 3 adrenergic receptor (β

Topics: Adrenergic beta-3 Receptor Agonists; Drug Approval; Female; Humans; Japan; Male; Middle Aged; Pyrimidinones; Pyrrolidines; Urinary Bladder, Overactive

Topics: Adrenergic beta-3 Receptor Agonists; Animals; Drug Interactions; Female; Humans; Macaca mulatta; Male; Muscarinic Antagonists; Muscle, Smooth; Protein Transport; Pyrimidinones; Pyrrolidines; Rats; Receptors, Adrenergic, beta-3; Species Specificity; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics

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

To evaluate the effects of orally administered YM976, a specific inhibitor of type 4 phosphodiesterase (PDE4), on bladder activity in a rat model with hydrochloric acid (HCl)-induced cystitis (IC), hypothesizing that a PDE4 inhibitor might suppress bladder overactivity and bladder pain responses in bladder-hypersensitive disorders such as IC.. Wistar rats with HCl-induced IC were treated with YM976 or vehicle and their voiding observed and assessed by cystometry. The severity of bladder inflammation (BI) was quantified using the BI index (BII), which comprises three factors (oedema, leukocyte infiltration and haemorrhage). Nociceptive neural activity was also examined using an immunohistochemical study of spinal c-fos expression.. YM976 significantly reduced the number of voids, and the volume per void was significantly higher than in control (vehicle) group. Cystometry showed a significant increase in bladder capacity, voided volume and voiding efficiency, and a decrease in the amplitude of voiding pressure in rats treated with YM976. All BII scores were significantly lower in the YM976 than in the control group. c-fos expression in the spine was less in the YM976 than in the control group.. Oral administration of YM976 significantly improved the voiding behaviour and histological damage in rats with IC induced by HCl. These results indicate that PDE4 inhibitor might be effective in relieving bladder symptoms with IC.

Topics: Animals; Cystitis, Interstitial; Female; Hydrochloric Acid; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Pyridines; Pyrimidinones; Rats; Rats, Wistar; Urinary Bladder, Overactive; Urodynamics