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Onset of action of the β3-adrenoceptor agonist, mirabegron, in Phase II and III clinical trials in patients with overactive bladder.

Chapple CR, Nitti VW, Khullar V, Wyndaele JJ, Herschorn S, van Kerrebroeck P, Blauwet MB, Siddiqui E - World J Urol (2014)

Bottom Line: Quality-of-life parameters also significantly improved with mirabegron 25 and 50 mg as early as week 4.Significant benefits continued throughout the studies.Mirabegron was well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Glossop Road, Sheffield, UK, c.r.chapple@shef.ac.uk.

ABSTRACT

Purpose: Long-term persistence with pharmacotherapy for overactive bladder (OAB) requires a drug with an early onset of action and good efficacy and tolerability profile. Although antimuscarinics improve OAB symptoms within 1-2 weeks of initiating treatment, adherence after 3 months is relatively poor due to bothersome side effects (e.g., dry mouth and constipation). Mirabegron, a β3-adrenoceptor agonist, has demonstrated significant improvements in key symptoms of OAB and good tolerability after 12 weeks in Phase III studies.

Methods: This was a prespecified pooled analysis of three randomized, double-blind, placebo-controlled, 12-week studies, and a Phase II study, to evaluate efficacy and tolerability of mirabegron 25 and 50 mg versus placebo. The main efficacy endpoints were change from baseline to week 1 (Phase II only), week 4, and final visit in mean number of incontinence episodes/24 h, micturitions/24 h, and mean volume voided/micturition (MVV).

Results: A significant benefit for mirabegron 25 and 50 mg versus placebo was evident at the first assessment point, 4 weeks after initiation of therapy, in Phase III studies for incontinence, micturitions, and MVV. The earliest measured benefit was after 1 week, in the Phase II study. Quality-of-life parameters also significantly improved with mirabegron 25 and 50 mg as early as week 4. Significant benefits continued throughout the studies. Mirabegron was well tolerated.

Conclusions: The early onset of action and good overall efficacy and tolerability balance that mirabegron offers may lead to high rates of persistence with mirabegron in the long-term treatment of OAB.

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Related in: MedlinePlus

Mean change from baseline (±SE) at each visit in the pooled Phase III studies: a the number of incontinence episodes/24 h (full analysis set-incontinence), b number of number of micturitions/24 h (full analysis set), and c volume voided/micturition (full analysis set). #Statistically significant treatment benefit relative to placebo (P < 0.05) with multiplicity adjustment. *Statistically significant treatment benefit relative to placebo (P < 0.05) without multiplicity adjustment. SE standard error, FAS full analysis set
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Fig2: Mean change from baseline (±SE) at each visit in the pooled Phase III studies: a the number of incontinence episodes/24 h (full analysis set-incontinence), b number of number of micturitions/24 h (full analysis set), and c volume voided/micturition (full analysis set). #Statistically significant treatment benefit relative to placebo (P < 0.05) with multiplicity adjustment. *Statistically significant treatment benefit relative to placebo (P < 0.05) without multiplicity adjustment. SE standard error, FAS full analysis set

Mentions: Mirabegron 50 mg demonstrated statistically significantly greater reductions from baseline to earliest measured assessment (week 4) and to final visit versus placebo for incontinence episodes/24 h, micturitions/24 h, and mean volume voided/micturition. Effectiveness was maintained throughout the treatment period (Fig. 2). Statistically significant differences versus placebo were also seen for mirabegron 50 mg at week 4 and final visit in mean number of urgency episodes (grades 3 or 4), urgency incontinence episodes/24 h, OAB-q Symptom Bother, HRQL total, and the Coping and Concern subscales.Fig. 2


Onset of action of the β3-adrenoceptor agonist, mirabegron, in Phase II and III clinical trials in patients with overactive bladder.

Chapple CR, Nitti VW, Khullar V, Wyndaele JJ, Herschorn S, van Kerrebroeck P, Blauwet MB, Siddiqui E - World J Urol (2014)

Mean change from baseline (±SE) at each visit in the pooled Phase III studies: a the number of incontinence episodes/24 h (full analysis set-incontinence), b number of number of micturitions/24 h (full analysis set), and c volume voided/micturition (full analysis set). #Statistically significant treatment benefit relative to placebo (P < 0.05) with multiplicity adjustment. *Statistically significant treatment benefit relative to placebo (P < 0.05) without multiplicity adjustment. SE standard error, FAS full analysis set
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4236626&req=5

Fig2: Mean change from baseline (±SE) at each visit in the pooled Phase III studies: a the number of incontinence episodes/24 h (full analysis set-incontinence), b number of number of micturitions/24 h (full analysis set), and c volume voided/micturition (full analysis set). #Statistically significant treatment benefit relative to placebo (P < 0.05) with multiplicity adjustment. *Statistically significant treatment benefit relative to placebo (P < 0.05) without multiplicity adjustment. SE standard error, FAS full analysis set
Mentions: Mirabegron 50 mg demonstrated statistically significantly greater reductions from baseline to earliest measured assessment (week 4) and to final visit versus placebo for incontinence episodes/24 h, micturitions/24 h, and mean volume voided/micturition. Effectiveness was maintained throughout the treatment period (Fig. 2). Statistically significant differences versus placebo were also seen for mirabegron 50 mg at week 4 and final visit in mean number of urgency episodes (grades 3 or 4), urgency incontinence episodes/24 h, OAB-q Symptom Bother, HRQL total, and the Coping and Concern subscales.Fig. 2

Bottom Line: Quality-of-life parameters also significantly improved with mirabegron 25 and 50 mg as early as week 4.Significant benefits continued throughout the studies.Mirabegron was well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Glossop Road, Sheffield, UK, c.r.chapple@shef.ac.uk.

ABSTRACT

Purpose: Long-term persistence with pharmacotherapy for overactive bladder (OAB) requires a drug with an early onset of action and good efficacy and tolerability profile. Although antimuscarinics improve OAB symptoms within 1-2 weeks of initiating treatment, adherence after 3 months is relatively poor due to bothersome side effects (e.g., dry mouth and constipation). Mirabegron, a β3-adrenoceptor agonist, has demonstrated significant improvements in key symptoms of OAB and good tolerability after 12 weeks in Phase III studies.

Methods: This was a prespecified pooled analysis of three randomized, double-blind, placebo-controlled, 12-week studies, and a Phase II study, to evaluate efficacy and tolerability of mirabegron 25 and 50 mg versus placebo. The main efficacy endpoints were change from baseline to week 1 (Phase II only), week 4, and final visit in mean number of incontinence episodes/24 h, micturitions/24 h, and mean volume voided/micturition (MVV).

Results: A significant benefit for mirabegron 25 and 50 mg versus placebo was evident at the first assessment point, 4 weeks after initiation of therapy, in Phase III studies for incontinence, micturitions, and MVV. The earliest measured benefit was after 1 week, in the Phase II study. Quality-of-life parameters also significantly improved with mirabegron 25 and 50 mg as early as week 4. Significant benefits continued throughout the studies. Mirabegron was well tolerated.

Conclusions: The early onset of action and good overall efficacy and tolerability balance that mirabegron offers may lead to high rates of persistence with mirabegron in the long-term treatment of OAB.

Show MeSH
Related in: MedlinePlus