Combination treatment with mirabegron and solifenacin in patients with overactive bladder: exploratory responder analyses of efficacy and evaluation of patient-reported outcomes from a randomized, double-blind, factorial, dose-ranging, Phase II study (SYMPHONY)

Abrams, Paul; Kelleher, Con; Kay, Richard; Martan, A; Minčík, I.; Newgreen, Donald; Ridder, Arwin; Paireddy, Asha; Maanen, Rob van

doi:10.1007/s00345-016-1908-1

Cited by 59 publications

(34 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A further consideration is that our study used 7‐day electronic diaries, which had previously been reported as having a higher reliability and accuracy for measuring micturition and incontinence in OAB patients compared with traditional 3‐day paper diaries . However, previous combination studies, including BESIDE and SYMPHONY, used 3‐day electronic diaries; therefore differences in the use of patient diaries may partially have contributed to differences in the efficacy outcomes between the studies …”

Section: Discussionmentioning

confidence: 98%

Patient‐reported outcomes from SYNERGY, a randomized, double‐blind, multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients

Robinson

Kelleher

Staskin

et al. 2017

Neurourology and Urodynamics

View full text Add to dashboard Cite

Funding informationAstellas Pharma Europe B.V Aims: To evaluate patient-reported outcomes (PROs) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial. Methods: Following a 4-week placebo run-in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg (combination 5 + 50 mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg, or placebo for 12 weeks, followed by a 2-week washout period. At each visit, PROs related to quality of life, symptom bother, and treatment satisfaction were assessed, including OAB-q Symptom Bother score, health-related quality of life (HRQOL), Total score, treatment satisfaction-visual analogue scale (TS-VAS), and patient perception of bladder condition (PPBC) questionnaires. Results: Overall, 3527 patients were randomized into the study, with 3494 receiving double-blind treatment. At end of treatment (EoT), both combination groups showed greater improvements in OAB-q Symptom Bother score compared with the monotherapy groups (nominal P < 0.001). Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus Alan Wein led the peer-review process as the Associate Editor responsible for the paper.394 |

show abstract

Section: Discussionmentioning

confidence: 98%

Patient‐reported outcomes from SYNERGY, a randomized, double‐blind, multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients

Robinson

Kelleher

Staskin

et al. 2017

Neurourology and Urodynamics

View full text Add to dashboard Cite

show abstract

“…If so, combining them with a muscarinic antagonist would be promising therapeutic. While initial data support this idea (Abrams et al, ), dedicated clinical trials are required to confirm it.…”

Section: Roles Of β3‐adrenoceptors In Pathophysiology Of Oabmentioning

confidence: 99%

β₃‐Adrenoceptors in the normal and diseased urinary bladder—What are the open questions?

Igawa

Aizawa

Michel

2019

British J Pharmacology

View full text Add to dashboard Cite

β3‐Adrenoceptor agonists are used in the treatment of overactive bladder syndrome. Although the relaxant response to adrenergic stimulation in human detrusor smooth muscle cells is mediated mainly via β3‐adrenoceptors, the plasma concentrations of the therapeutic dose of mirabegron, the only clinically approved β3‐adrenoceptor agonist, are considerably lower than the EC50 for causing direct relaxation of human detrusor, suggesting a mechanism of action other than direct relaxation of detrusor smooth muscle. However, the site and mechanism of action of β3‐adrenoceptor agonists in the bladder have not been firmly established. Postulated mechanisms include prejunctional suppression of ACh release from the parasympathetic nerves during the storage phase and inhibition of micro‐contractions through β3‐adrenoceptors on detrusor smooth muscle cells or suburothelial interstitial cells. Implications of possible desensitization of β3‐adrenoceptors in the bladder upon prolonged agonist exposure and possible causes of rarely observed cardiovascular effects of mirabegron are also discussed. Linked Articles This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc

show abstract

“…Combination pharmacotherapy for lower urinary tract symptoms (LUTS) is a well‐accepted concept for a number of conditions, often using agents that address different mechanisms of actions . Using this idea, we evaluated the combination therapy for OAB and nocturia, with tolterodine – an antimuscarinic, and desmopressin – a synthetic analogue of arginine vasopressin.…”

Section: Introductionmentioning

confidence: 99%

Low‐dose Desmopressin and Tolterodine Combination Therapy for Treating Nocturia in Women with Overactive Bladder: A Double‐blind, Randomized, Controlled Study

Raymond

Andruczyk²,

Juul

2017

LUTS

View full text Add to dashboard Cite

show abstract

Combination treatment with mirabegron and solifenacin in patients with overactive bladder: exploratory responder analyses of efficacy and evaluation of patient-reported outcomes from a randomized, double-blind, factorial, dose-ranging, Phase II study (SYMPHONY)

Abstract: Combining mirabegron 25/50 mg and solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg.

Cited by 59 publications

References 29 publications

Patient‐reported outcomes from SYNERGY, a randomized, double‐blind, multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients

Patient‐reported outcomes from SYNERGY, a randomized, double‐blind, multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients

β₃‐Adrenoceptors in the normal and diseased urinary bladder—What are the open questions?

Low‐dose Desmopressin and Tolterodine Combination Therapy for Treating Nocturia in Women with Overactive Bladder: A Double‐blind, Randomized, Controlled Study

Contact Info

Product

Resources

About

Combination treatment with mirabegron and solifenacin in patients with overactive bladder: exploratory responder analyses of efficacy and evaluation of patient-reported outcomes from a randomized, double-blind, factorial, dose-ranging, Phase II study (SYMPHONY)

Abstract: Combining mirabegron 25/50 mg and solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg.

Cited by 59 publications

References 29 publications

Patient‐reported outcomes from SYNERGY, a randomized, double‐blind, multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients

Patient‐reported outcomes from SYNERGY, a randomized, double‐blind, multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients

β3‐Adrenoceptors in the normal and diseased urinary bladder—What are the open questions?

Low‐dose Desmopressin and Tolterodine Combination Therapy for Treating Nocturia in Women with Overactive Bladder: A Double‐blind, Randomized, Controlled Study

Contact Info

Product

Resources

About

β₃‐Adrenoceptors in the normal and diseased urinary bladder—What are the open questions?