Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE)

Marcus Drake; Christopher Chapple; Ahmet Esen; Stavros Athanasiou; Javier Cambronero; David Mitcheson; Sender Herschorn; Tahir Saleem; Moses Huang; Emad Siddiqi; Matthias  Stölzel; Claire  Herholdt; Scott  MacDiarmid

doi:10.1016/j.eururo.2016.02.030

Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE)

Marcus Drake, Christopher Chapple, Ahmet Esen, Stavros Athanasiou, Javier Cambronero, David Mitcheson, Sender Herschorn, Tahir Saleem, Moses Huang, Emad Siddiqi, Matthias Stölzel, Claire Herholdt, Scott MacDiarmid

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Background: Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic mono therapy.

Objective: To evaluate efficacy, safety/tolerability of combination (solifenacin5 mg/mirabegron 50 mg) vs solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4-wk solifenacin 5 mg.

Design, Setting, and Participants: OAB patients remaining incontinent despitedaily solifenacin 5 mg during 4-wk single-blind run-in, were randomised 1:1:1 to double-blind daily combination, solifenacin 5 or 10 mg for 12 wk. Patients receiving combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4.

Outcome Measurements and Statistical Analysis: Primary endpoint: change from baseline to end of treatment (EOT) in mean number of incontinence episodes/24 (stratified rank ANCOVA). Key secondary endpoints: change from baseline to EOT in mean number of micturitions/24 h (ANCOVA) and number of incontinence episodes during 3-d diary at EOT (mixed effects Poisson regression). BESIDE tested the superiority of combination vs solifenacin 5 mg, noninferiority (and potential superiority) of combination vs solifenacin 10 mg (key secondary endpoints), and safety/tolerability of combination vs Solifenacin monotherapy.

Results and Limitations: 2174 patients were randomised: combination (n=727), solifenacin 5mg (n=728) or 10 mg (n=719). At EOT, combination was superior to solifenacin 5 mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001) and incontinence during 3-d diary (p=0.014). Combination was noninferior to BESIDE Primary Final resubmission draft January 2016 4 solifenacin 10 mg for key secondary endpoints, and superior vs solifenacin 10 mg for improving daily micturitions. All treatments were well tolerated.

Conclusions: Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms vs solifenacin 5 or 10 mg, and was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg

Original language	English
Pages (from-to)	136-145
Number of pages	10
Journal	European Urology
Volume	70
Issue number	1
Early online date	8 Mar 2016
DOIs	https://doi.org/10.1016/j.eururo.2016.02.030
Publication status	Published - Jul 2016

Research Groups and Themes

Centre for Surgical Research

Keywords

Add-on therapy
Incontinence
Mirabegron
Overactive bladder
Solifenacin

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Dive into the research topics of 'Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE)'. Together they form a unique fingerprint.

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Drake, M., Chapple, C., Esen, A., Athanasiou, S., Cambronero, J., Mitcheson, D., Herschorn, S., Saleem, T., Huang, M., Siddiqi, E., Stölzel, M., Herholdt, C., & MacDiarmid, S. (2016). Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE). European Urology, 70(1), 136-145. https://doi.org/10.1016/j.eururo.2016.02.030

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title = "Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE)",

abstract = "Background: Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic mono therapy. Objective: To evaluate efficacy, safety/tolerability of combination (solifenacin5 mg/mirabegron 50 mg) vs solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4-wk solifenacin 5 mg. Design, Setting, and Participants: OAB patients remaining incontinent despitedaily solifenacin 5 mg during 4-wk single-blind run-in, were randomised 1:1:1 to double-blind daily combination, solifenacin 5 or 10 mg for 12 wk. Patients receiving combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4. Outcome Measurements and Statistical Analysis: Primary endpoint: change from baseline to end of treatment (EOT) in mean number of incontinence episodes/24 (stratified rank ANCOVA). Key secondary endpoints: change from baseline to EOT in mean number of micturitions/24 h (ANCOVA) and number of incontinence episodes during 3-d diary at EOT (mixed effects Poisson regression). BESIDE tested the superiority of combination vs solifenacin 5 mg, noninferiority (and potential superiority) of combination vs solifenacin 10 mg (key secondary endpoints), and safety/tolerability of combination vs Solifenacin monotherapy. Results and Limitations: 2174 patients were randomised: combination (n=727), solifenacin 5mg (n=728) or 10 mg (n=719). At EOT, combination was superior to solifenacin 5 mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001) and incontinence during 3-d diary (p=0.014). Combination was noninferior to BESIDE Primary Final resubmission draft January 2016 4 solifenacin 10 mg for key secondary endpoints, and superior vs solifenacin 10 mg for improving daily micturitions. All treatments were well tolerated. Conclusions: Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms vs solifenacin 5 or 10 mg, and was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg",

keywords = "Add-on therapy, Incontinence, Mirabegron, Overactive bladder, Solifenacin",

author = "Marcus Drake and Christopher Chapple and Ahmet Esen and Stavros Athanasiou and Javier Cambronero and David Mitcheson and Sender Herschorn and Tahir Saleem and Moses Huang and Emad Siddiqi and Matthias St{\"o}lzel and Claire Herholdt and Scott MacDiarmid",

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language = "English",

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Drake, M, Chapple, C, Esen, A, Athanasiou, S, Cambronero, J, Mitcheson, D, Herschorn, S, Saleem, T, Huang, M, Siddiqi, E, Stölzel, M, Herholdt, C & MacDiarmid, S 2016, 'Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE)', European Urology, vol. 70, no. 1, pp. 136-145. https://doi.org/10.1016/j.eururo.2016.02.030

Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE). / Drake, Marcus; Chapple, Christopher; Esen, Ahmet et al.
In: European Urology, Vol. 70, No. 1, 07.2016, p. 136-145.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy

T2 - A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE)

AU - Drake, Marcus

AU - Chapple, Christopher

AU - Esen, Ahmet

AU - Athanasiou, Stavros

AU - Cambronero, Javier

AU - Mitcheson, David

AU - Herschorn, Sender

AU - Saleem, Tahir

AU - Huang, Moses

AU - Siddiqi, Emad

AU - Stölzel, Matthias

AU - Herholdt, Claire

AU - MacDiarmid, Scott

PY - 2016/7

Y1 - 2016/7

N2 - Background: Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic mono therapy. Objective: To evaluate efficacy, safety/tolerability of combination (solifenacin5 mg/mirabegron 50 mg) vs solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4-wk solifenacin 5 mg. Design, Setting, and Participants: OAB patients remaining incontinent despitedaily solifenacin 5 mg during 4-wk single-blind run-in, were randomised 1:1:1 to double-blind daily combination, solifenacin 5 or 10 mg for 12 wk. Patients receiving combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4. Outcome Measurements and Statistical Analysis: Primary endpoint: change from baseline to end of treatment (EOT) in mean number of incontinence episodes/24 (stratified rank ANCOVA). Key secondary endpoints: change from baseline to EOT in mean number of micturitions/24 h (ANCOVA) and number of incontinence episodes during 3-d diary at EOT (mixed effects Poisson regression). BESIDE tested the superiority of combination vs solifenacin 5 mg, noninferiority (and potential superiority) of combination vs solifenacin 10 mg (key secondary endpoints), and safety/tolerability of combination vs Solifenacin monotherapy. Results and Limitations: 2174 patients were randomised: combination (n=727), solifenacin 5mg (n=728) or 10 mg (n=719). At EOT, combination was superior to solifenacin 5 mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001) and incontinence during 3-d diary (p=0.014). Combination was noninferior to BESIDE Primary Final resubmission draft January 2016 4 solifenacin 10 mg for key secondary endpoints, and superior vs solifenacin 10 mg for improving daily micturitions. All treatments were well tolerated. Conclusions: Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms vs solifenacin 5 or 10 mg, and was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg

AB - Background: Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic mono therapy. Objective: To evaluate efficacy, safety/tolerability of combination (solifenacin5 mg/mirabegron 50 mg) vs solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4-wk solifenacin 5 mg. Design, Setting, and Participants: OAB patients remaining incontinent despitedaily solifenacin 5 mg during 4-wk single-blind run-in, were randomised 1:1:1 to double-blind daily combination, solifenacin 5 or 10 mg for 12 wk. Patients receiving combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4. Outcome Measurements and Statistical Analysis: Primary endpoint: change from baseline to end of treatment (EOT) in mean number of incontinence episodes/24 (stratified rank ANCOVA). Key secondary endpoints: change from baseline to EOT in mean number of micturitions/24 h (ANCOVA) and number of incontinence episodes during 3-d diary at EOT (mixed effects Poisson regression). BESIDE tested the superiority of combination vs solifenacin 5 mg, noninferiority (and potential superiority) of combination vs solifenacin 10 mg (key secondary endpoints), and safety/tolerability of combination vs Solifenacin monotherapy. Results and Limitations: 2174 patients were randomised: combination (n=727), solifenacin 5mg (n=728) or 10 mg (n=719). At EOT, combination was superior to solifenacin 5 mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001) and incontinence during 3-d diary (p=0.014). Combination was noninferior to BESIDE Primary Final resubmission draft January 2016 4 solifenacin 10 mg for key secondary endpoints, and superior vs solifenacin 10 mg for improving daily micturitions. All treatments were well tolerated. Conclusions: Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms vs solifenacin 5 or 10 mg, and was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg

KW - Add-on therapy

KW - Incontinence

KW - Mirabegron

KW - Overactive bladder

KW - Solifenacin

U2 - 10.1016/j.eururo.2016.02.030

DO - 10.1016/j.eururo.2016.02.030

M3 - Article (Academic Journal)

C2 - 26965560

SN - 0302-2838

VL - 70

SP - 136

EP - 145

JO - European Urology

JF - European Urology

IS - 1

ER -

Drake M, Chapple C, Esen A, Athanasiou S, Cambronero J, Mitcheson D et al. Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE). European Urology. 2016 Jul;70(1):136-145. Epub 2016 Mar 8. doi: 10.1016/j.eururo.2016.02.030