Results of a Randomized Phase III Trial of Mirabegron in Patients with Overactive Bladder

Νitti, Victor W.; Auerbach, Stephen M.; Martin, Nancy; Calhoun, Alaina; Lee, Misun; Herschorn, Sender

doi:10.1016/j.juro.2012.10.017

Cited by 324 publications

(277 citation statements)

References 23 publications

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“…The low incidence of AEs with mirabegron including antimuscarinic-associated AEsdry mouth, constipation and blurred vision -is very consistent with phase III trials where mirabegron demonstrated rates similar to placebo [Herschorn et al 2013;Khullar et al 2013a;Nitti et al 2013a]. Despite a lower incidence of antimuscarinic AEs and lower than expected rates of discontinuation with solifenacin compared with previous studies [Chapple et al 2006], which was presumably due to the exclusion of treatmentnaive patients and patients dissatisfied with previous antimuscarinics solely or primarily due to poor tolerability, the incidence of dry mouth was lower with mirabegron compared with solifenacin.…”

Section: Discussionsupporting

confidence: 67%

The efficacy and safety of mirabegron compared with solifenacin in overactive bladder patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy: results of a noninferiority, randomized, phase IIIb trial

Batista

Kölbl

Herschorn

et al. 2015

Therapeutic Advances in Urology

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Objective: To compare the efficacy and safety of mirabegron 50 mg and solifenacin 5 mg in overactive bladder (OAB) patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy. Patients and methods: This randomized, double-blind, phase IIIb, noninferiority study, enrolled male and female patients aged ⩾18 years old, with symptoms of OAB for ⩾3 months, who were dissatisfied with their previous antimuscarinic drug due to lack of efficacy. A total of 1887 patients were randomized to receive mirabegron 50 mg (n = 943) or solifenacin 5 mg (n = 944) daily for 12 weeks. The primary efficacy endpoint was change from baseline to end of treatment in mean number of micturitions/24 h. Noninferiority was confirmed if the lower limit of the two-sided 95% confidence interval (CI) for the treatment difference between solifenacin and mirabegron was > −0.20. Secondary efficacy endpoints, which included change from baseline in mean number of incontinence episodes/24 h, urgency incontinence episodes/24 h, urgency episodes (grade 3 or 4)/24 h and nocturia episodes/24 h, were analyzed using analysis of covariance. Results: For the primary endpoint, adjusted mean treatment difference (95% CI) in mean number of micturitions/24 h was −0.18 (−0.42, 0.06) and therefore noninferiority of mirabegron to solifenacin was not demonstrated. Both treatments demonstrated clinically meaningful reductions in efficacy variables and were well tolerated, with a lower incidence of dry mouth with mirabegron. Conclusions: Noninferiority of mirabegron compared with solifenacin for reduction in micturition frequency could not be demonstrated in this population of OAB patients who were dissatisfied with previous antimuscarinic therapy due to lack of efficacy. Both mirabegron and solifenacin improved key OAB symptoms with no statistically significant differences observed between the two treatments. Both drugs were well tolerated.

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Section: Discussionsupporting

confidence: 67%

The efficacy and safety of mirabegron compared with solifenacin in overactive bladder patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy: results of a noninferiority, randomized, phase IIIb trial

Batista

Kölbl

Herschorn

et al. 2015

Therapeutic Advances in Urology

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“…Mirabegron, [2-(2-amino-1,3-thiazol-4-yl)-N-[4-(2-ethyl) phenyl]-acetamide] is a β 3 -adrenergic receptor agonist used for the treatment of overactive bladder. [26][27][28] Mirabegron was provided by Astellas Pharma Inc. (Tokyo, Japan). SLS was purchased from Cognis GmbH (Monheim, Germany).…”

Section: Methodsmentioning

confidence: 99%

Oral Sustained Release of a Hydrophilic Drug Using the Lauryl Sulfate Salt/Complex

Kasashima

Yoshihara

Yasuji

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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The objective of this study was to establish the key factor of the lauryl sulfate (LS) salt/complex for sustained release of a hydrophilic drug at various physiological pH levels. Mirabegron is a hydrophilic drug that exhibits pH-dependent solubility. Sodium lauryl sulfate (SLS) bound to mirabegron in a stoichiometric manner. The formation of the LS salt/complex significantly reduced mirabegron solubility and helped achieve sustained release of mirabegron over a wide range of pH levels. In addition to SLS, other additives containing a sulfate group formed salts/complexes with mirabegron and reduced its solubility at different pH levels. Furthermore, octyl sulfate (OS), myristyl sulfate (MS), and cetyl sulfate (CS) salts/complexes, which contain alkyl chains of different lengths, showed a lower solubility than mirabegron and promoted sustained release of mirabegron. The rank order of solubility and dissolution rate were as follows: OS salt/complex>LS salt/ complex>MS salt/complex>CS salt/complex, which corresponded to the rank of alkyl chain lengths. We conclude that the presence of a sulfate group and the length of the alkyl chain are key factors of the LS salt/ complex for sustained release of a hydrophilic drug at various physiological pH levels.

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“…Mirabegron is the first β3 agonist to be used in clinical practice. [50][51][52][53] (D) To assess the efficacy and tolerability of this drug therapy in the treatment of idiopathic overactive bladder (IOAB), two phase II 54,55 (B) and six phase III [56][57][58][59][60][61] (A) randomized clinical trials (RCTs) recruited more than 10,500 adult patients. Of these, seven were randomized, double-blind and placebo-controlled with follow-up of four (one study) and 12 (six studies) weeks, and one was non-placebo-controlled (vs. tolterodine) with 12-month follow-up.…”

Section: Tolterodine Tartratementioning

confidence: 99%

Overactive bladder: pharmacological treatment

Sacomani

Almeida

Silvinato

et al. 2017

Rev. Assoc. Med. Bras.

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

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Results of a Randomized Phase III Trial of Mirabegron in Patients with Overactive Bladder

Abstract: Once daily mirabegron in a 50 or 100 mg dose is an effective treatment for overactive bladder symptoms with a low occurrence of side effects.

Cited by 324 publications

References 23 publications

The efficacy and safety of mirabegron compared with solifenacin in overactive bladder patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy: results of a noninferiority, randomized, phase IIIb trial

The efficacy and safety of mirabegron compared with solifenacin in overactive bladder patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy: results of a noninferiority, randomized, phase IIIb trial

Oral Sustained Release of a Hydrophilic Drug Using the Lauryl Sulfate Salt/Complex

Overactive bladder: pharmacological treatment

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