A Phase III, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicentre Study to Assess the Efficacy and Safety of the β3 Adrenoceptor Agonist, Mirabegron, in Patients With Symptoms of Overactive Bladder

Herschorn, Sender; Barkin, Jack; Castro-Díaz, David; Frankel, Jeffrey; Espuña‐Pons, Montserrat; Gousse, Angelo E.; Stölzel, Matthias; Martin, Nancy; Gunther, Adrie; Kerrebroeck, Philip Van

doi:10.1016/j.urology.2013.02.077

Cited by 226 publications

(226 citation statements)

References 16 publications

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“…In four 12-week phase III studies [Herschorn et al 2013;Khullar et al 2013a;Nitti et al 2013a;Yamaguchi et al 2014], a pooled analysis [Nitti et al 2013b] and 12-month study [Chapple et al 2013], mirabegron (25-100 mg) consistently demonstrated superiority over placebo with respect to reductions in incontinence episodes and micturition frequency, with a similar incidence of AEs as placebo.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…In recent large Phase III clinical trials, mirabegron has demonstrated significant efficacy over placebo in treating the symptoms of OAB, including micturition frequency, urgency incontinence, and urgency [25][26] . Given IC/BPS similar overlying symptomatology with OAB in terms of urgency related symptoms, we hypothesized that mirabegron may also play a role in treating that subset of symptoms in the IC/BPS population.…”

Section: Cuaj -Original Research DI Lena Et Al Mirabegron For Ic/bps mentioning

confidence: 99%

Mirabegron as adjuvant treatment for patients with interstitial cystitis/bladder pain syndrome

Lena

Tolls

Kelly

et al. 2017

CUAJ

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Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) patients represent a heterogeneous group with pain and urinary storage symptoms and varying responses to current treatment options. The novel beta-3 agonist, mirabegron, has been shown to improve storage symptoms of patients with bladder overactivity; however, its effect on symptoms in the IC/BPS population has yet to be studied. Methods: Patients diagnosed at a single IC centre with IC/BPS undergoing standard therapy were treated with additional daily mirabegron 25 mg and seen in followup post-treatment. Patients completed the Interstitial Cystitis Symptom Index and Problem Index (ICSI/ICPI), and the Pelvic Pain and Urgency/Frequency Patient Symptom Scale (PUF) prior to and following mirabegron treatment. Global (NRS) and symptom-specific outcomes were assessed by comparing the pre-and post-treatment mean scores using tailed-t test (p<0.05 considered statistically significant). Results: A total of 23 patients were available for review pre-and post-mirabegron treatment. There was no significant difference in ICSI (p=0.448), ICPI (p=0.352), or PUF (p=0.869) preand post-treatment. Analysis of symptom-specific outcomes show statistically significant improvements in urgency (p=0.048); however, no statistically significant improvements in frequency (p=0.951) or pain (p=0.952) were observed with mirabegron therapy. Conclusions: IC/BPS patients treated with mirabegron had improvement of urinary urgency, but no significant benefit in terms of pain or urinary frequency. This data suggests that mirabegron's role in the IC/BPS patient should be that of adjuvant treatment to ameliorate urgency.

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A Phase III, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicentre Study to Assess the Efficacy and Safety of the β3 Adrenoceptor Agonist, Mirabegron, in Patients With Symptoms of Overactive Bladder

Cited by 226 publications

References 16 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

Mirabegron as adjuvant treatment for patients with interstitial cystitis/bladder pain syndrome

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