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2.
Urol Pract ; 11(2): 392-393, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38215019
3.
J Comp Eff Res ; 12(9): CER, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37586052

RESUMEN

What is this summary about? This is a plain language summary of an article published in the journal Advances in Therapy. In 2020, the US Food and Drug Administration (also called the FDA) approved a medicine called vibegron to treat overactive bladder, also called OAB. The key results used to approve vibegron were from the EMPOWUR study. In the EMPOWUR study, participants who took vibegron had fewer urination episodes, urgency episodes, and bladder leaks each day than those who took a pill containing no medicine, called a placebo. At the end of the study, participants also rated how much their overactive bladder symptoms changed overall during EMPOWUR by responding to a survey. Many participants rated their overactive bladder symptoms as improved overall. This study asked if improvements in the number of urination episodes, urgency episodes, and bladder leaks caused by urgency were associated with feeling better overall. This study also looked at how many participants in the EMPOWUR study had improvements in the number of urination episodes, urgency episodes, and bladder leaks that were big enough to matter. A separate group of people with overactive bladder were asked about the magnitude of improvements that would be important to them. This group had not participated in the EMPOWUR study. What were the results? EMPOWUR participants who reported that taking medicine resulted in their overactive bladder symptoms getting better overall also generally reported fewer daily urinations, urgency episodes, and bladder leaks after treatment. Many had changes in their symptoms that were meaningful. Meaningful was defined for each symptom as: at least 15% fewer urinations, 50% fewer urgency episodes, and 75% fewer bladder leaks. Participants who received vibegron had meaningful reductions in the daily number of episodes of urination, urgency, and bladder leaks more often than those who received the placebo (pill with no active medicine). People with overactive bladder who did not participate in the study were interviewed and said that improvements to those symptoms, similar to those seen in the EMPOWUR study, would be important to them. What do the results mean? This study suggests that the results we measured in the EMPOWUR study may also reflect changes in overactive bladder symptoms that are big enough to be important to people with overactive bladder. Many participants who took vibegron in the EMPOWUR study felt that it helped to improve their individual overactive bladder symptoms. This may also help improve quality of life of participants. Clinical Trial Registration: NCT03492281 (ClinicalTrials.gov).


Asunto(s)
Vejiga Urinaria Hiperactiva , Humanos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Calidad de Vida , Resultado del Tratamiento , Micción
4.
J Comp Eff Res ; 12(9): CER, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37586057

RESUMEN

What is this summary about? This is a plain language summary of an article originally published in the Journal of Urology. Overactive bladder (also called OAB) has been treated with the same type of medicine for more than 40 years. Vibegron is in a newer class of medicine for treating overactive bladder called beta-3 adrenergic receptor agonists. The EMPOWUR study was a phase 3 clinical trial that looked at whether vibegron was safe and improved symptoms in people with overactive bladder. Vibegron was approved by the US Food and Drug Administration (also called the FDA) based in part on the results of this study. What were the results? Participants of the EMPOWUR study who took vibegron showed an improvement in their overactive bladder symptoms. These symptoms include the number of urinations (peeing), the urgent need to urinate, and accidental urination (bladder leaks). After 12 weeks, participants who took vibegron had significantly greater improvements than participants who took placebo. What do the results mean? This study suggests that vibegron could safely improve symptoms in people with overactive bladder. Clinical Trial Registration: NCT03492281 (ClinicalTrials.gov).


Asunto(s)
Vejiga Urinaria Hiperactiva , Humanos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Resultado del Tratamiento , Agonistas de Receptores Adrenérgicos beta 3/uso terapéutico , Método Doble Ciego
5.
J Med Primatol ; 52(4): 283-285, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37248799

RESUMEN

A cynomolgus macaque presented with right hindlimb lameness as well as crepitus and decreased passive range of motion of the right coxal joint. Radiography and histopathology were consistent with avascular necrosis of the femoral head. This case is the first published report of this condition in a cynomolgus macaque.


Asunto(s)
Necrosis de la Cabeza Femoral , Animales , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Necrosis de la Cabeza Femoral/veterinaria , Necrosis de la Cabeza Femoral/patología , Macaca fascicularis , Radiografía , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/patología
6.
Urol Pract ; 10(2): 160, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37103422
7.
Urol Pract ; 10(3): 252, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37103507
8.
Int J Clin Pract ; 2022: 6475014, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35685566

RESUMEN

Background: 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 ß 3-adrenergic receptor agonist for the treatment of OAB-significantly improved daily number of urgency episodes and micturitions vs. placebo (P < 0.01). These post hoc analyses aimed to compare the efficacy of vibegron vs. placebo in OAB dry and wet populations. Methods: 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. Results: Of the 1463 patients included in the full analysis set, 336 (23%) had OAB dry (vibegron, N = 123; placebo, N = 115; and tolterodine, N = 98), and 1127 (77%) had OAB wet (vibegron, N = 403; placebo, N = 405; and tolterodine, N = 319). Vibegron was associated with significant reductions (95% CIs of the least squares mean differences [LSMD] does not include 0) from baseline at week 12 vs. placebo in mean daily urgency episodes for the dry (LSMD [95% CI], ‒1.0 [‒2.0, ‒0.1]) and wet (‒0.6 [‒1.0, ‒0.1]) populations. Vibegron was associated with significant reductions from baseline at week 12 vs. placebo in mean daily micturitions for the dry (LSMD [95% CI], ‒0.8 [‒1.5, ‒ 0.1]) and wet (‒0.5 [‒0.8, ‒0.1]) populations. There were no significant differences in either outcome between tolterodine and placebo for either the dry or wet populations in this study. Conclusions: 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.


Asunto(s)
Vejiga Urinaria Hiperactiva , Método Doble Ciego , Humanos , Pirimidinonas , Pirrolidinas , Tartrato de Tolterodina/uso terapéutico , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/complicaciones , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Incontinencia Urinaria de Urgencia
9.
Ther Clin Risk Manag ; 18: 171-182, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35264853

RESUMEN

Pharmacologic treatment for overactive bladder (OAB), which is characterized by bothersome symptoms such as urgency and urge urinary incontinence (UUI), includes anticholinergics and ß3-adrenergic receptor agonists. Anticholinergics are associated with adverse effects including dry mouth, constipation, cognitive impairment, and increased risk of dementia. Therefore, the drug class of ß3-adrenergic receptor agonists may represent an effective, safe treatment option. Vibegron, a ß3-adrenergic receptor agonist, was approved for use in Japan (2018) and the United States (2020). Over the past 3 years, 2 phase 3 trials (EMPOWUR, EMPOWUR extension) have been conducted with once-daily vibegron 75 mg for the treatment of OAB, and additional secondary and subgroup analyses have detailed the efficacy and safety of vibegron. In the international phase 3 EMPOWUR trial, treatment with vibegron was associated with significant improvements compared with placebo in efficacy outcomes of micturition frequency, UUI episodes, urgency episodes, and volume voided as early as week 2 that were sustained throughout the 12-week trial. The 40-week EMPOWUR extension study, following the 12-week treatment period, demonstrated sustained efficacy in patients receiving vibegron for 52 weeks. Treatment with vibegron was also associated with improvements in patient-reported measures of quality of life. Across studies, vibegron was generally safe and well tolerated. A separate, dedicated ambulatory blood pressure monitoring study showed that treatment with vibegron was not associated with clinically meaningful effects on blood pressure or heart rate. Across all studies, vibegron was efficacious, safe, and well tolerated and thus represents a valuable treatment option for patients with OAB. Here, nearly 1 year after US approval, we review the published data on efficacy and safety of vibegron 75 mg for the treatment of OAB.

10.
Am J Cancer Res ; 12(1): 445-450, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35141028

RESUMEN

Apalutamide, an androgen receptor signaling inhibitor, in combination with androgen-deprivation therapy (ADT), is approved for treatment of patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer, based on the data from the phase 3 SPARTAN and TITAN studies respectively. Apalutamide is an inducer of cytochrome P450 enzymes and P-glycoprotein, which are involved in the metabolism of oral anticoagulants (OACs) and may thus have potential drug-drug interactions when co-administered with OACs. Concomitant use of certain OACs such as apixaban, rivaroxaban, edoxaban, dabigatran, and warfarin was allowed in the SPARTAN and TITAN studies. A post-hoc analysis was conducted to evaluate the incidence of treatment-emergent thrombotic and embolic adverse events (AEs) in patients receiving concomitant OACs with apalutamide + ADT or placebo + ADT in both the studies. Anticoagulants were identified by WHO Drug Anatomical Therapeutic Chemical level 4 classifications. Thrombotic and embolic AEs were coded using the Medical Dictionary for Regulatory Activities Version 22.1. Data were analyzed from patients receiving concurrent OACs among all treated patients in SPARTAN (apalutamide + ADT: 95/803 [11.8%]; placebo + ADT: 48/398 [12.1%]) and TITAN (apalutamide + ADT: 31/524 [5.9%]; placebo + ADT: 28/527 [5.3%]). No consequential differences were observed in the occurrence of thrombotic and embolic events between apalutamide + ADT and placebo + ADT groups receiving concomitant OACs in SPARTAN (11.6% vs 12.5%) or TITAN (19.4% vs 21.4%). Grade 3/4 thrombotic and embolic AEs observed in patients receiving concomitant OACs with apalutamide + ADT or placebo + ADT were 6 (6.3%) vs 5 (10.4%) in SPARTAN and 3 (9.7%) vs 1 (3.6%) in TITAN. This analysis suggests that when necessary, concomitant OACs can be used with apalutamide with appropriate monitoring.

11.
Adv Ther ; 39(2): 959-970, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34921665

RESUMEN

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier, NCT03492281.


Asunto(s)
Vejiga Urinaria Hiperactiva , Método Doble Ciego , Humanos , Antagonistas Muscarínicos/uso terapéutico , Pirimidinonas/uso terapéutico , Pirrolidinas , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/tratamiento farmacológico
12.
J Urol ; 205(5): 1429, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33687277
13.
Drugs Aging ; 38(2): 137-146, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33469832

RESUMEN

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03492281; registered April 10, 2018.


Asunto(s)
Vejiga Urinaria Hiperactiva , Anciano , Método Doble Ciego , Humanos , Pirimidinonas , Pirrolidinas , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/tratamiento farmacológico
14.
Int J Clin Pract ; 75(5): e13937, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33332699

RESUMEN

BACKGROUND: Quality of life (QOL) can be significantly impacted by symptoms of overactive bladder (OAB). Vibegron is a highly selective ß3 -adrenergic receptor agonist that showed efficacy in treatment of symptoms of OAB in the randomised, double-blind, placebo- and active-controlled phase 3 EMPOWUR trial. Here we report patient-reported QOL outcomes from the EMPOWUR trial. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier number NCT03492281.


Asunto(s)
Calidad de Vida , Vejiga Urinaria Hiperactiva , Método Doble Ciego , Humanos , Antagonistas Muscarínicos/uso terapéutico , Medición de Resultados Informados por el Paciente , Pirimidinonas , Pirrolidinas , Tartrato de Tolterodina/uso terapéutico , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/tratamiento farmacológico
15.
J Urol ; 205(5): 1421-1429, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33356445

RESUMEN

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Vibegron demonstrated favorable long-term safety, tolerability and efficacy in patients with overactive bladder, consistent with results of the 12-week study.


Asunto(s)
Antagonistas Muscarínicos/uso terapéutico , Pirimidinonas/administración & dosificación , Pirrolidinas/administración & dosificación , Tartrato de Tolterodina/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Anciano , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pirimidinonas/efectos adversos , Pirrolidinas/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
16.
J Urol ; 204(2): 324, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32436760
17.
J Urol ; 204(2): 316-324, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32068484

RESUMEN

PURPOSE: We assessed efficacy, safety and tolerability of vibegron, a novel, potent, highly selective ß3-adrenoceptor agonist, administered 12 weeks at 75 mg once daily to patients with overactive bladder in an international phase III trial with placebo and active control. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Asunto(s)
Agonistas de Receptores Adrenérgicos beta 3/uso terapéutico , Pirimidinonas/uso terapéutico , Pirrolidinas/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Adulto , Anciano , Preparaciones de Acción Retardada , Método Doble Ciego , Femenino , Humanos , Internacionalidad , Masculino , Persona de Mediana Edad , Tartrato de Tolterodina/uso terapéutico , Agentes Urológicos/uso terapéutico
18.
Am J Primatol ; 81(12): e23061, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31713260

RESUMEN

Despite careful attention to animal nutrition and wellbeing, gastrointestinal distress remains relatively common in captive non-human primates (NHPs), particularly dietary specialists such as folivores. These patterns may be a result of marked dietary differences between captive and wild settings and associated impacts on the gut microbiome. However, given that most existing studies target NHP dietary specialists, it is unclear if captive environments have distinct impacts on the gut microbiome of NHPs with different dietary niches. To begin to examine this question, we used 16S ribosomal RNA gene amplicon sequences to compare the gut microbiomes of five NHP genera categorized either as folivores (Alouatta, Colobus) or non-folivores (Cercopithecus, Gorilla, Pan) sampled both in captivity and in the wild. Though captivity affected the gut microbiomes of all NHPs in this study, the effects were largest in folivorous NHPs. Shifts in gut microbial diversity and in the relative abundances of fiber-degrading microbial taxa suggest that these findings are driven by marked dietary shifts for folivorous NHPs in captive settings. We propose that zoos and other captive care institutions consider including more natural browse in folivorous NHP diets and regularly bank fecal samples to further explore the relationship between NHP diet, the gut microbiome, and health outcomes.


Asunto(s)
Animales de Laboratorio/microbiología , Animales de Zoológico/microbiología , Dieta/veterinaria , Microbioma Gastrointestinal , Primates/microbiología , Animales , Animales de Laboratorio/fisiología , Animales de Zoológico/fisiología , Dieta/clasificación , Preferencias Alimentarias , Primates/fisiología , ARN Bacteriano/análisis , ARN Ribosómico 16S/análisis , Especificidad de la Especie
19.
J Clin Pharmacol ; 58(8): 1084-1091, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29645285

RESUMEN

There have been concerns that treatment of overactive bladder with ß3 -adrenoceptor agonists may potentially have detrimental cardiovascular (CV) side effects. We evaluated the CV safety of mirabegron, a ß3 -adrenoceptor agonist, alone and in combination therapy with the antimuscarinic agent solifenacin. The SYNERGY trial was a multinational, multicenter, randomized, double-blind, parallel-group, placebo and active-controlled phase 3 trial. Patients were randomized to receive solifenacin 5 mg + mirabegron 50 mg (combination 5 + 50 mg), solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg monotherapy, mirabegron 25 mg monotherapy, mirabegron 50 mg monotherapy, or placebo for a 12-week double-blind treatment period. A total of 3398 patients were included in the study. Mean changes from baseline to the end of therapy in ECG parameters were similar across treatment groups, although there was an increase in heart rate of 1 beat/minute in the mirabegron treatment groups. There were no clinically meaningful differences in change from baseline in QTcF between monotherapies and placebo and between monotherapies and combination therapy. There were very few major CV events: 1 of 853 (0.1%) with a nonfatal myocardial infarction in the combination 5 + 25 mg group, 2 of 848 (0.2%) with a nonfatal stroke in the combination 5 + 50 mg group, and no events in the other groups. This CV safety analysis of the combination of mirabegron and solifenacin showed rates of CV events comparable with those for monotherapy treatments based on assessments of vital signs, electrocardiograms, and adjudicated CV events.

20.
Blood Press Monit ; 23(3): 153-163, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29578880

RESUMEN

OBJECTIVE: The aim of this study was to perform a blood pressure (BP) safety evaluation in patients with an overactive bladder receiving solifenacin (an antimuscarinic agent), mirabegron (a ß3-adrenoceptor agonist), or both compared with placebo in the SYNERGY trial. PATIENTS AND METHODS: Patients were randomized to receive solifenacin 5 mg+mirabegron 50 mg (combination 5+50 mg); solifenacin 5 mg+mirabegron 25 mg (combination 5+25 mg); solifenacin 5 mg; mirabegron 50 mg; mirabegron 25 mg; or placebo for a double-blind 12-week treatment period. Systolic BP, diastolic BP, and heart rate were measured by ambulatory BP monitoring, and in the clinic or home. RESULTS: A total of 715 patients were analyzed in an ambulatory BP monitoring substudy. At the end of treatment, ambulatory BP monitoring measurements showed no consistent increases from baseline in the mean 24-h systolic BP or diastolic BP for combination versus monotherapy groups or for monotherapy groups versus placebo. Analysis of 1-h BP averages during the 6 h range that included the Tmax values of both study drugs showed no significant BP effects. Shift analysis (switch between different normotension/hypertension stages) did not show differences among the active and placebo groups, nor did outlier analysis of major BP changes differ between placebo and active treatment. Similarly, there were no significant signals in the 24-h heart rate. Office and home measurements were consistent with ambulatory BP monitoring findings. CONCLUSIONS: A paradigm of ambulatory BP monitoring analysis designed to test BP safety of noncardiovascular drugs showed that solifenacin plus mirabegron combination therapy during 12 weeks produced no meaningful changes in BP or heart rate.


Asunto(s)
Acetanilidas/farmacología , Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Succinato de Solifenacina/farmacología , Tiazoles/farmacología , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad
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