Impact of mirabegron extended-release on the treatment of overactive bladder with urge urinary incontinence, urgency, and frequency

Figures & data

Table 1 Multi-trial comparisons of coprimary efficacy endpoints and quality of life measures

	Nitti et al^Citation41			Khullar et al^Citation39			Van Kerrebroeck et al^Citation40
	PBO	Mirabegron 50 mg	Mirabegron 100 mg	PBO	Mirabegron 50 mg	Mirabegron 100 mg	PBO	Mirabegron 25 mg	Mirabegron 50 mg
Coprimary efficacy endpoints
Incontinence episodes per 24 hours (FAS-I)
n	325	312	296	291	293	281	262	254	257
Baseline (mean)	3	2.8	2.7	2.67	2.83	2.89	2.43§	2.65§	2.51§
Change from baseline	−1.13	−1.47#	−1.63#	−1.17	−1.57	−1.46	−0.96	−1.36	−1.38
Difference from PBO	NA	−0.34	−0.5	NA	−0.41	−0.29	NA	−0.40	−0.42
95% CL	NA	(−0.66, −0.3)§	NR	NA	(−0.72, −0.09)	(−0.61, 0.03)	NA	(−0.74, −0.06)§	(−0.76,−0.08)§
P value	NA	0.026§	NR	NA	0.003#	0.010#	NA	0.005#	0.001#
Micturitions per 24 hours (FAS)
n	433	425	412	480	473	478	415	410	426
Baseline (mean)	11.5	11.8	11.7	11.71	11.65	11.51	11.48§	11.68§	11.66§
Change from baseline	−1.05	−1.66#	−1.75#	−1.34	−1.93	−1.77	−1.18	−1.65	−1.60
Difference from PBO	NA	−0.61	−0.70	NA	−0.60	−0.44	NA	−0.47	−0.42
95% CL	NA	NR	NR	NA	(−0.90, −0.29)	(−0.74, −0.13)	NA	(−0.82, −0.13)§	(−0.76, −0.08)§
P value	NA	NR	NR	NA	< 0.001#	0.005#	NA	0.007#	0.015#
Quality of life measures
Treatment satisfaction visual analog scale (TS-VAS)¶
Mean (SE)	0.70 (0.16)	1.55 (0.16)	2.09 (0.16)♮	1.89 (0.146)	2.55 (0.149)♮	2.66 (0.146)♮	1.05	1.54♮	1.88♮
Mean diff from PBO (SE)	NR	NR	NR	NA	0.66 (0.208)	0.77 (0.207)	NR	NR	NR
95% CL	(0.4, 1.0)	(1.2, 1.9)	(1.8, 2.4)	NA	(0.25–1.07)	(0.36–1.17)	(0.75,1.35)	(1.24, 1.84)	(1.58, 2.18)
P value	NA	< 0.05	< 0.05	NA	0.001	,0.001	NA	0.024	,0.001
Overactive bladder questionnaire (OAB-q) Symptom Bother Score¶
Mean (SE)	−10.8 (0.97)	−17.0 (0.98)♮	−20.2 (0.99)♮	−14.9 (0.84)	−19.6 (0.85)♮	−19.9 (0.84)♮	−16	−17.9♮	−18.8♮
Mean diff from PBO (Se)	NR	NR	NR	NA	−4.17 (1.19)	−5.0 (1.19)	NR	NR	NR
95% CL	(−12.7, −8.9)	(−18.9, −15.1)	(−22.1, −18.2)	NA	(−7.1 to −2.4)	(−7.3 to −2.6)	(−17.8, −14.3)	(−19.6, −16.1)	(−20.5, −17.1)
P-value	NA	< 0.05	< 0.05	NA	< 0.001	< 0.001	NA	0.15	0.028
Patient perception of bladder condition (PPBC)¶
Mean (SE)	−0.5 (0.1)	−0.7 (0.1)♮	−0.8 (0.1)♮	−0.8 (0.05)	−1.0 (0.06)♮	−1.1 (0.05)♮	−0.7	−0.8♮	−0.7♮
Mean diff from PBO (SE)	NR	NR	NR	NA	−0.2 (0.08)	−0.2 (0.08)	NR	NR	NR
95% CL	(−0.6, −0.4)	(−0.8, −0.6)	(−0.9, 0.7)	NA	(−0.3 to −0.0)	(−0.4 to −0.01)	(−0.8, −0.6)	(−0.9, −0,6)	(−0.8, −0.6)
P-value	NA	<0.05	<0.05	NA	0.045	0.001	NA	0.49	0.64

Notes: Data are adjusted mean changes from baseline generated from the analysis of covariance (ANCOVA) model with treatment group, sex, and geographic region as fixed factors, and baseline as a covariate. Data are for the FAS (full analysis set), except for incontinence outcomes, which are for the FAS-I. P-values are pairwise comparisons versus placebo in the ANCOVA model or stratified rank ANCOVA model for incontinence outcomes. Data from Astellas Prescribing Information;³⁸ Nitti et al;⁴¹ Khullar et al;³⁹ and Van Kerrebroeck et al.⁴⁰

§ data from Andersson.¹³

# P < 0.05 with multiplicity adjustment.

♮ P < 0.05 without multiplicity adjustment.

¶ for TS-VAS an increase in value indicates improvement. For OAB-q Symptom Bother Score and PPBC a decrease in value indicates improvement.

Abbreviations: PBO, placebo; CI, confidence interval; FAS-I, full analysis set incontinence; FAS, full analysis set; NR, not reported; NA, not applicable; SE, standard error; TS-VAS, treatment satisfaction visual analog scale; OAB-q, overactive bladder questionnaire; PPBC, patient perception of bladder condition.

Table 2 Reported treatment-related adverse events of mirabegron ≥ 2%

Adverse events	Khullar et al^Citation39,§			Nitti et al^Citation41,§			Van Kerrebroeck et al^Citation40,#
	Placebo	Mirabegron 50 mg	Mirabegron 100 mg	Placebo	Mirabegron 50 mg	Mirabegron 100 mg	Placebo	Mirabegron 25 mg	Mirabegron 50 mg
Hypertension	7.7%	5.9%	5.4%	6.6%	6.1%	4.9%	8.5%	11.3%	10.7%
Nasopharyngitis	1.6%	2.8%	2.8%	2.9%	3.4%	2.5%	3.2%	3.5%	5.7%
Dry mouth	2.6%	2.8%	2.8%	1.5%	0.5%	2.1%	*	*	*
Headache	2.8%	3.7%	1.8%	2.0%	3.2%	3.0%	4.4%	2.1%	2.7%
Influenza	1.6%	2.2%	2.0%	NR	NR	NR	NR	NR	NR
Sinusitis	NR	NR	NR	2.2%	2.0%	2.1%	NR	NR	NR
Upper respiratory tract infection	*	*	*	2.5%	2.7%	2.1%	1.3%	2.1%	1.6%
Urinary tract infection	*	*	*	1.8%	2.7%	3.7%	3.3%	4.2%	4.8%
Diarrhea	NR	NR	NR	1.3%	2.7%	2.1%	NR	NR	NR

Notes:

* Reported but < 2% for treatment groups

§ includes events reported from first dose of double-blind treatment until 30 days after the last dose of double-blind study drug

# includes events reported from first dose of double-blind treatment until 14 days after the last dose of double-blind study drug.

Abbreviation: NR, not reported.

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