Randomized Double-blind, Active-controlled Phase 3 Study to Assess 12-Month Safety and Efficacy of Mirabegron, a β3-Adrenoceptor Agonist, in Overactive Bladder

doi:10.1016/J.EURURO.2012.10.048

Home
/
Papers
/
Randomized Double-blind, Active-controlled Phase 3 Study to Assess 12-Month Safety and Efficacy of Mirabegron, a β3-Adrenoceptor Agonist, in Overactive Bladder

Journal Article•DOI•

Randomized Double-blind, Active-controlled Phase 3 Study to Assess 12-Month Safety and Efficacy of Mirabegron, a β3-Adrenoceptor Agonist, in Overactive Bladder

Christopher R. Chapple¹, Steven A. Kaplan², David Mitcheson, Jiri Klecka, Jana Cummings³, T. Drogendijk³, Caroline Dorrepaal³, Nancy Martin³ - Show less +4 more•Institutions (3)

Royal Hallamshire Hospital¹, Cornell University², Center for Global Development³

01 Feb 2013-European Urology (Elsevier)-Vol. 63, Iss: 2, pp 296-305

TL;DR: Mirabegron and the active control, tolterodine, improved key OAB symptoms from the first measured time point of 4 wk, and efficacy was maintained throughout the 12-mo treatment period.

read less

About: This article is published in European Urology.The article was published on 2013-02-01. It has received 302 citations till now. The article focuses on the topics: Mirabegron & Tolterodine.

...read moreread less

Citations

PDF

Open Access

More filters

Journal Article•DOI•

Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline

[...]

E. Ann Gormley¹, Deborah J. Lightner¹, Kathryn L. Burgio¹, Toby C. Chai¹, J. Quentin Clemens¹, Daniel J. Culkin¹, Anurag K. Das¹, Harris E. Foster¹, Harriette Miles Scarpero¹, Christopher Tessier¹, Sandip Prasan Vasavada¹ - Show less +7 more•Institutions (1)

American Urological Association¹

01 Dec 2012-The Journal of Urology

TL;DR: This guideline provides a clinical framework for the diagnosis and treatment of non-neurogenic overactive bladder and identifies first through third line treatments as well as non-FDA approved, rarely applicable and treatments that should not be offered.

...read moreread less

643 citations

Cites background from "Randomized Double-blind, Active-con..."

...One of the Phase III trials followed patients for one year.(133) Inclusion criteria were similar across studies, generally...
[...]
...143 In addition, compliance with a once-daily treatment has been shown to be greater than with medications that are taken more than once a day.(133) The decision to prescribe an IR versus an ER formulation, however, should be made in the context of the patient’s prior experience with antimuscarinics and the availability of medications, including insurer constraints, in order to minimize patient burden....
[...]

Journal Article•DOI•

Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment

[...]

Deborah J. Lightner¹, Alexander Gomelsky¹, Lesley Souter¹, Sandip Prasan Vasavada¹•Institutions (1)

American Urological Association¹

01 May 2015-The Journal of Urology

TL;DR: This guideline amendment focused on four topic areas: mirabegron, peripheral tibial nerve stimulation, sacral neuromodulation and BTX-A.

...read moreread less

640 citations

Cites background from "Randomized Double-blind, Active-con..."

...One of the Phase III trials followed patients for one year.(12)...
[...]

Journal Article•DOI•

EAU Guidelines on Assessment and Nonsurgical Management of Urinary Incontinence

[...]

Arjun Nambiar¹, Ruud Bosch², Francisco Cruz, Gary E. Lemack³, Nikesh Thiruchelvam⁴, Andrea Tubaro⁵, Dina Bedretdinova⁶, David Ambühl, Fawzy Farag⁷, Riccardo Lombardo⁵, Marc P. Schneider, Fiona C. Burkhard - Show less +8 more•Institutions (7)

Freeman Hospital¹, University Medical Center Utrecht², University of Texas Southwestern Medical Center³, University of Cambridge⁴, Sapienza University of Rome⁵, French Institute of Health and Medical Research⁶, Sohag University⁷

01 Dec 2012-European Urology

TL;DR: The previous European Association of Urology (EAU) guidelines on urinary incontinence comprised a summary of sections of the 2009 International Consultation on Incontinence as mentioned in this paper, and a decision was made in 2010 to rewrite these guidelines based on an independent systematic review carried out by the EAU guidelines panel.

...read moreread less

351 citations

Journal Article•DOI•

Comparative Efficacy and Safety of Medical Treatments for the Management of Overactive Bladder: A Systematic Literature Review and Mixed Treatment Comparison

[...]

K. Maman, Samuel Aballéa, Jameel Nazir¹, Katia Desroziers, Mohamed-Elmoctar Neine, Emad Siddiqui¹, Isaac Odeyemi¹, Zalmai Hakimi² - Show less +4 more•Institutions (2)

Astellas Pharma¹, Center for Global Development²

01 Apr 2014-European Urology

TL;DR: It is shown that mirabegron 50 mg was as efficacious as antimuscarinics in reducing the frequency of micturition incontinence and UUI episodes and lower incidence of dry mouth, the most common adverse event reported with antimus carinics and one of the main causes of discontinuation of treatment.

...read moreread less

227 citations

Journal Article•DOI•

Mirabegron in overactive bladder: A review of efficacy, safety, and tolerability

[...]

Christopher R. Chapple¹, Linda Cardozo², Victor W. Nitti³, Emad Siddiqui⁴, Martin C. Michel⁵ - Show less +1 more•Institutions (5)

Royal Hallamshire Hospital¹, University of Cambridge², New York University³, Astellas Pharma⁴, University of Mainz⁵

01 Jan 2014-Neurourology and Urodynamics

TL;DR: Data is presented on the efficacy, safety, and tolerability of mirabegron in studies conducted to date that demonstrate a different mechanism of action from antimuscarinic agents.

...read moreread less

Abstract: Aims Mirabegron, the first β3-adrenoceptor agonist to enter clinical practice, has a different mechanism of action from antimuscarinic agents. This review presents data on the efficacy, safety, and tolerability of mirabegron in studies conducted to date. Methods All clinical data on mirabegron that are currently in the public domain are included, including some in-press manuscripts. Results In Phase III clinical trials in patients with overactive bladder (OAB), mirabegron at daily doses of 25, 50, and 100 mg demonstrated significant efficacy in treating the symptoms of OAB, including micturition frequency, urgency incontinence, and urgency. Significant improvements in micturition frequency, urgency incontinence, and mean volume voided/micturition were seen as early as the first assessment (week 4) for mirabegron 50 and 100 mg, and were maintained throughout treatment. Responder analyses showed a significant improvement with mirabegron 50 and 100 mg in terms of dry rates, ≥50% reduction in mean number of incontinence episodes/24 hr, and the proportion of patients with ≤8 micturitions/24 hr at final visit. The benefit of mirabegron 50 and 100 mg was also evident in patients ≥65 years of age, and in both treatment-naive patients and those who previously discontinued antimuscarinic therapy. These data therefore demonstrate a clinically meaningful benefit with mirabegron in the objective endpoints of OAB. Assessment of measures of health-related quality of life and treatment satisfaction showed that patients perceived treatment with mirabegron as meaningful. In OAB clinical trials of up to 12 months mirabegron appeared to be well tolerated. The most common adverse events (AEs) observed with mirabegron in clinical trials of up to 12 months were hypertension, nasopharyngitis, and urinary tract infection. The incidence of dry mouth was similar to placebo, and was between three and fivefold less than for tolterodine extended release 4 mg. Since dry mouth is the most bothersome AE associated with antimuscarinic drugs and often a reason for treatment discontinuation, mirabegron may be a valuable treatment option for these patients. Conclusions In Phase III clinical trials, mirabegron at daily doses of 25, 50, and 100 mg demonstrated significant efficacy in treating symptoms of OAB and, at doses of 50 and 100 mg, demonstrated significant improvements versus placebo on key secondary endpoints, as early as the first assessment (week 4), and these were maintained throughout treatment. In OAB clinical trials of up to 12 months, mirabegron appeared to be well tolerated. Neurourol. Urodynam. 33:17–30, 2014. © 2013 Wiley Periodicals, Inc.

...read moreread less

227 citations

Cites background or methods or result from "Randomized Double-blind, Active-con..."

...A blinded independent data safety monitoring board (DSMB) inspection of SAEs, discontinuation rates, overall AEs and treatment-emergent AEs, clinical laboratory assessments, vital signs, and ECG readings concluded that there were no relevant safety concerns across the treatment groups during or at the end of the study.(39) Therewere no clinically relevant effects on post-void residual (PVR) volume in BLOSSOM....
[...]
...9 bpm for PM measurements).(39) The change from baseline to final visit for pulse rate in patients receiving mirabegron 50mg was approximately 1 bpm....
[...]
...6mm Hg for PM measurements.(39) No consistent trends in ECG changes were identified, and categorical outliers for QTc interval assessments were unremarkable across treatment groups....
[...]
...Although the 12-month TAURUS study did not include a placebo arm and was not designed to demonstrate a statistically significant difference in efficacy between treatment groups,mirabegron 50 and 100mg showed numerical improvements in OAB-q Symptom Bother, HRQL Total scores and subscores, and on the TS-VAS and PPBC (Table VI).(39) The consistent pattern of significant results in favor of mirabegron over placebo on the PRO measures suggests that mirabegron provides positive and meaningful changes in symptom-specific bother, HRQL, and patients’ perception of their bladder condition; in parallel with the improvements reported for diary-based endpoints....
[...]
...In such patients, the response to tolterodine was similar to placebo.38 A 12-month, multinational, randomized, double-blind, parallel-group, active-controlled, Phase III trial (TAURUS [Study 178-CL-049; NCT00688688]), assessed mirabegron 50 and 100mg and tolterodine ER 4mg QD.39 Although the study was not designed to demonstrate a statistically significant difference in efficacy between treatment groups, mirabegron 50 and 100mg and tolterodine ER 4mg showed numerical improvements from months 1–12 in mean number of micturitions/24hr, incontinence episodes/24 hr, and mean volume voided/micturition....
[...]

1
2
3
4
…
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

The Effects of Antimuscarinic Treatments in Overactive Bladder: An Update of a Systematic Review and Meta-Analysis

[...]

Christopher R. Chapple¹, Vik Khullar², Zahava Gabriel, Dominic Muston, Caty Ebel Bitoun³, David Weinstein³ - Show less +2 more•Institutions (3)

Royal Hallamshire Hospital¹, Imperial College London², Pfizer³

01 Sep 2008-European Urology

TL;DR: Antimuscarinics are efficacious, safe, and well-tolerated treatments that improve HRQL and should be considered in making treatment choices.

...read moreread less

713 citations

"Randomized Double-blind, Active-con..." refers background in this paper

...In the 12-wk phase 3 studies, the incidence of dry mouth with mirabegron was similar to placebo [7,8], which may potentially translate into better adherence to OAB treatment, given that dry mouth is the sentinel AE of the current mainstay of therapy that limits adherence [1,9]....
[...]

Journal Article•DOI•

Results of a randomized phase III trial of mirabegron in patients with overactive bladder.

[...]

Victor W. Nitti¹, Stephen Auerbach², Nancy Martin³, Alaina Calhoun³, Misun Lee³, Sender Herschorn⁴ - Show less +2 more•Institutions (4)

New York University¹, NewYork–Presbyterian Hospital², Center for Global Development³, University of Toronto⁴

01 Apr 2013-The Journal of Urology

TL;DR: 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.

...read moreread less

386 citations

"Randomized Double-blind, Active-con..." refers background in this paper

...In the 12-wk phase 3 studies, the incidence of dry mouth with mirabegron was similar to placebo [7,8], which may potentially translate into better adherence to OAB treatment, given that dry mouth is the sentinel AE of the current mainstay of therapy that limits adherence [1,9]....
[...]
...Approximately 2500 patients were planned for enrollment, based on estimates of numbers enrolling after completing studies NCT00689104 and NCT00662909....
[...]
...profile of mirabegron following 12-mo exposure is consistent with that seen in 12-wk phase 3 studies [7,8]....
[...]
...Recent phase 3 trials have demonstrated the efficacy and safety of mirabegron for up to 12 wk of therapy (NCT00689104 and NCT00662909) [7,8]....
[...]

Journal Article•DOI•

Re: Efficacy and Tolerability of Mirabegron, a β3-Adrenoceptor Agonist, in Patients with Overactive Bladder: Results from a Randomised European-Australian Phase 3 Trial

[...]

Alan J. Wein¹•Institutions (1)

Imperial College London¹

01 Feb 2013-European Urology

TL;DR: Mirabegron represents a new class of treatment for OAB with proven efficacy and good tolerability and Statistically significant improvements were also observed in other key efficacy end points and QoL outcomes.

...read moreread less

382 citations

"Randomized Double-blind, Active-con..." refers background in this paper

...In the 12-wk phase 3 studies, the incidence of dry mouth with mirabegron was similar to placebo [7,8], which may potentially translate into better adherence to OAB treatment, given that dry mouth is the sentinel AE of the current mainstay of therapy that limits adherence [1,9]....
[...]
...Approximately 2500 patients were planned for enrollment, based on estimates of numbers enrolling after completing studies NCT00689104 and NCT00662909....
[...]
...profile of mirabegron following 12-mo exposure is consistent with that seen in 12-wk phase 3 studies [7,8]....
[...]
...Recent phase 3 trials have demonstrated the efficacy and safety of mirabegron for up to 12 wk of therapy (NCT00689104 and NCT00662909) [7,8]....
[...]

Journal Article•DOI•

Muscarinic receptor antagonists for overactive bladder

[...]

Paul Abrams¹, Karl-Erik Andersson¹•Institutions (1)

Wake Forest Institute for Regenerative Medicine¹

01 Nov 2007-BJUI

TL;DR: An in‐depth review of drugs that are available for the treatment of common conditions, written by two of the leading authorities in the world, Paul Abrams and Karl‐Erik Andersson, on the topic of overactive bladder and antimuscarinic agents.

...read moreread less

Abstract: Overactive bladder (OAB) is a syndrome characterized by urinary urgency, with or without urgency urinary incontinence, usually with frequency and nocturia. OAB symptoms are often associated with detrusor overactivity (DO). Like OAB symptoms, the prevalence of DO increases with age and can have a neurogenic and/or myogenic aetiology. Bladder outlet obstruction can be a contributing factor in DO, possibly through cholinergic denervation of the detrusor and supersensitivity of muscarinic receptors to acetylcholine, although the prevalence of OAB is similar in men and women across age groups. Acetylcholine is the primary contractile neurotransmitter in the human detrusor, and antimuscarinics exert their effects on OAB/DO by inhibiting the binding of acetylcholine at muscarinic receptors M(2) and M(3) on detrusor smooth muscle cells and other structures within the bladder wall. Worldwide, there are six antimuscarinic drugs currently marketed for the treatment of OAB: oxybutynin, tolterodine, propiverine, trospium, darifenacin, and solifenacin. Each has demonstrated efficacy for the treatment of OAB symptoms, but their pharmacokinetic and adverse event profiles differ somewhat due to structural differences (tertiary vs quaternary amines), muscarinic receptor subtype selectivities, and organ selectivities. Antimuscarinics are generally well tolerated, even in special populations (e.g. men with bladder outlet obstruction, elderly patients, children). The most frequently reported adverse events in clinical studies of antimuscarinics are dry mouth, constipation, headache, and blurred vision; few patients withdraw from clinical trials because of adverse events. Development of an antimuscarinic with functional selectivity for the bladder would reduce the occurrence of antimuscarinic adverse events. The therapeutic potential of several other agents, such as alpha(3)-adrenoceptor agonists, purinergic receptor antagonists, phosphodiesterase inhibitors, neurokinin-1 receptor antagonists, opioids, and Rho-kinase inhibitors, is also under investigation for the treatment of OAB.

...read moreread less

357 citations

"Randomized Double-blind, Active-con..." refers background in this paper

...In the 12-wk phase 3 studies, the incidence of dry mouth with mirabegron was similar to placebo [7,8], which may potentially translate into better adherence to OAB treatment, given that dry mouth is the sentinel AE of the current mainstay of therapy that limits adherence [1,9]....
[...]
...For several decades, oral antimuscarinic agents have represented the current mainstay of pharmacotherapy for improving overactive bladder (OAB) symptoms; however, they may elicit inadequate response in some patients, and/ or their use may be associated with adverse events (AEs) (eg, dry mouth, constipation, and blurred vision) [1,2]....
[...]

Journal Article•DOI•

Efficacy and adverse events of antimuscarinics for treating overactive bladder: network meta-analyses.

[...]

Nora Buser¹, Sandra Ivic, Thomas M. Kessler¹, Alfons G. H. Kessels², Lucas M. Bachmann - Show less +1 more•Institutions (2)

University of Zurich¹, Maastricht University Medical Centre²

01 Dec 2012-European Urology

TL;DR: This is the first study allowing trade-offs between efficacy and adverse events of various drugs and dosages in the treatment of patients with OAB and differences among the various antimuscarinics call for careful, patient-centered management in which regimen changes should be considered.

...read moreread less

153 citations

"Randomized Double-blind, Active-con..." refers background in this paper

...For several decades, oral antimuscarinic agents have represented the current mainstay of pharmacotherapy for improving overactive bladder (OAB) symptoms; however, they may elicit inadequate response in some patients, and/ or their use may be associated with adverse events (AEs) (eg, dry mouth, constipation, and blurred vision) [1,2]....
[...]