Table 1.
Multi-trial comparisons of coprimary efficacy endpoints and quality of life measures
| Nitti et al41
|
Khullar et al39
|
Van Kerrebroeck et al40
|
|||||||
|---|---|---|---|---|---|---|---|---|---|
| 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.