Introduction
Materials and methods
Study patients
Study design and procedures
Study endpoints
Statistical analysis
Results
Study patients
Characteristic | Placebo | Mirabegron OCASc
| Tolterodine ER | |||
---|---|---|---|---|---|---|
(n = 166) | 25 mg (n = 167) | 50 mg (n = 167) | 100 mg (n = 168) | 200 mg (n = 166) | 4 mgc (n = 85) | |
Age (years) ± SD | 57.1 ± 12.9 | 57.2 ± 12.1 | 56.9 ± 12.5 | 57.1 ± 12.5 | 58.0 ± 13.7 | 56.6 ± 12.8 |
Sex, n (%) | ||||||
Male | 15 (9.0) | 20 (12.0) | 18 (10.8) | 17 (10.1) | 12 (7.2) | 16 (18.8) |
Female | 151 (91.0) | 147 (88.0) | 149 (89.2) | 151 (89.9) | 154 (92.8) | 69 (81.2) |
Race, n (%) | ||||||
Asian | 0 | 1 (0.6) | 0 | 1 (0.6) | 0 | 2 (2.4) |
Black | 0 | 2 (1.2) | 0 | 0 | 0 | 0 |
White | 166 (100) | 162 (97.0) | 162 (97.0) | 167 (99.4) | 164 (98.8) | 81 (95.3) |
Other | 0 | 1 (0.6) | 3 (1.8) | 0 | 0 | 1 (1.2) |
Missing | 0 | 1 (0.6) | 2 (1.2) | 0 | 2 (1.2) | 1 (1.2) |
Type of OAB, n (%) | ||||||
Urge incontinence only | 74 (44.6) | 79 (47.3) | 67 (40.1) | 67 (39.9) | 63 (38.0) | 38 (44.7) |
Mixed incontinenceb
| 52 (31.3) | 41 (24.6) | 47 (28.1) | 54 (32.1) | 63 (38.0) | 24 (28.2) |
Without incontinence | 40 (24.1) | 47 (28.1) | 53 (31.7) | 47 (28.0) | 40 (24.1) | 23 (27.1) |
Prior drug therapy, n (%) | ||||||
Yes, at least one effective | 41 (24.7) | 40 (24.0) | 39 (23.4) | 42 (25.0) | 34 (20.5) | 19 (22.4) |
Yes, none effective | 30 (18.1) | 42 (25.1) | 38 (22.8) | 39 (23.2) | 38 (22.9) | 16 (18.8) |
No | 95 (57.2) | 85 (50.9) | 90 (53.9) | 87 (51.8) | 94 (56.6) | 50 (58.8) |
Non-drug therapy, n (%) | 51 (30.7) | 57 (34.1) | 49 (29.3) | 44 (26.2) | 40 (24.1) | 22 (25.9) |
Primary efficacy endpoint
Placebo | Mirabegron OCASb
| Tolterodine ERc
| ||||
---|---|---|---|---|---|---|
25 mg | 50 mg | 100 mg | 200 mg | 4 mg | ||
Micturitions/24 h |
n = 166 |
n = 167 |
n = 167 |
n = 168 |
n = 166 |
n = 85 |
Adjusted mean CFB | −1.44 | −1.88 | −2.08 | −2.12 | −2.24 | −1.99 |
Estimated difference from placebo | −0.45 | −0.64* | −0.68* | −0.80** | −0.52 | |
95 % CIs | −0.99, 0.10 | −1.19 , −0.10 | −1.22, −0.13 | −1.34, −0.25 | −1.18, 0.15 | |
Mean volume voided/micturition (ml) |
n = 165 |
n = 167 |
n = 167 |
n = 168 |
n = 166 |
n = 85 |
Adjusted mean CFB | 7.29 | 15.32 | 27.34 | 25.56 | 33.34 | 23.86 |
Estimated difference from placebo | 8.03 | 20.05*** | 18.28*** | 26.06*** | 16.81* | |
95 % CIs | −1.54, 17.60 | 10.48, 29.63 | 8.66, 27.89 | 16.49, 35.62 | 5.09, 28.5 | |
Incontinence episodes/24 h |
n = 106 |
n = 99 |
n = 108 |
n = 111 |
n = 110 |
n = 53 |
Adjusted mean CFB | −0.53 | −1.36 | −1.15 | −1.06 | −1.10 | −0.81 |
Estimated difference from placebo | −0.84** | −0.62* | −0.53 | −0.58 | −0.28 | |
95 % CIs | −1.45, −0.23 | −1.22, −0.02 | −1.12, 0.06 | −1.16, 0.01 | −1.01, 0.45 | |
Nocturia episodes/24 h |
n = 144 |
n = 145 |
n = 142 |
n = 141 |
n = 147 |
n = 72
|
Adjusted mean CFB | −0.38 | −0.52 | −0.60 | −0.42 | −0.59 | −0.59 |
Estimated difference from placebo | −0.15 | −0.22* | −0.04 | −0.21 | −0.21 | |
95 % CIs | −0.36, 0.07 | −0.44, −0.01 | −0.26, 0.17 | −0.43, 0.00 | −0.47, 0.05 | |
Urgency incontinence episodesa/24 h |
n = 106 |
n = 93 |
n = 106 |
n = 107 |
n = 108 |
n = 52
|
Adjusted mean CFB | −0.44 | −1.31 | −1.13 | −1.18 | −1.24 | −0.76 |
Estimated difference from placebo | −0.86** | −0.69** | −0.74** | −0.80** | −0.31 | |
95 % CIs | −1.38, −0.35 | −1.18, −0.19 | −1.23, −0.25 | −1.29, −0.31 | −0.92, 0.30 | |
Urgency episodes/24 h (severity ≥3) |
n = 165 |
n = 167 |
n = 166 |
n = 168 |
n = 165 |
n = 85
|
Adjusted mean CFB | −1.07 | −1.77 | −1.67 | −2.28 | −2.48 | −1.46 |
Estimated difference from placebo | −0.70* | −0.60 | −1.21*** | −1.42*** | −0.37 | |
95 % CIs | −1.38, −0.01 | −1.29, 0.08 | −1.90, −0.52 | −2.10, −0.73 | −1.21, 0.47 | |
Level of urgency/24 h |
n = 166 |
n = 166 |
n = 166 |
n = 168 |
n = 166 |
n = 85 |
Adjusted mean CFB | −0.10 | −0.21 | −0.18 | −0.29 | −0.38 | −0.14 |
Estimated difference from placebo | −0.12 | −0.08 | −0.19** | −0.28*** | −0.04 | |
95 % CIs | −0.25, 0.02 | −0.22, 0.05 | −0.33, −0.06 | −0.41, −0.15 | −0.21, 0.12 | |
ICIQ-OAB |
n = 166 |
n = 167 |
n = 166 |
n = 168 |
n = 166 |
n = 85 |
Adjusted mean CFB | −1.82 | −2.40 | −2.51 | −2.72 | −3.02 | −2.21 |
Estimated difference from placebo | −0.58* | −0.69* | −0.90** | −1.20*** | −0.37 | |
95 % CIs | −1.13, −0.02 | −1.24, −0.13 | −1.45, −0.34 | −1.76, −0.65 | −1.05, 0.31 | |
ICIQ-OABqol |
n = 162 |
n = 163 |
n = 165 |
n = 163 |
n = 162 |
n = 84 |
Adjusted mean CFB | −16.11 | −17.09 | −20.36 | −20.57 | −22.19 | −17.42 |
Estimated difference from placebo | −0.98 | −4.25 | −4.46 | −6.08* | −1.32 | |
95 % CIs | −5.88, 3.92 | −9.13, 0.62 | −9.37, 0.46 | −11.0, −1.19 | −7.32, 4.69 |
Placebo | Mirabegron OCASb
| Tolterodine ERb
| ||||
---|---|---|---|---|---|---|
25 mg | 50 mg | 100 mg | 200 mg | 4 mg | ||
Patients, n (%)c
| ||||||
Micturitions/24 h* |
n = 166 |
n = 167 |
n = 167 |
n = 168 |
n = 166 |
n = 85 |
32 (19.3) | 48 (28.7) | 46 (27.5) | 55 (32.7) | 50 (30.1) | 16 (18.8) | |
Incontinence episodes/24 h* |
n = 106 |
n = 99 |
n = 108 |
n = 111 |
n = 110 |
n = 53 |
39 (36.8) | 42 (42.4) | 45 (41.7) | 62 (55.9) | 53 (48.2) | 19 (35.8) | |
Urgency episodes (grade ≥ 3)/24 h |
n = 165 |
n = 167 |
n = 166 |
n = 168 |
n = 165 |
n = 85 |
25 (15.2) | 27 (16.2) | 24 (14.5) | 33 (19.6) | 36 (21.8) | 13 (15.3) | |
Nocturia episodes/24 h |
n = 144 |
n = 145 |
n = 142 |
n = 141 |
n = 147 |
n = 72 |
21 (14.6) | 34 (23.4) | 34 (23.9) | 20 (14.2) | 34 (23.1) | 13 (18.1) |
Secondary efficacy endpoints
Urinary symptoms
Quality of life
Safety
System organ class preferred term | Placebo (n = 169) | Mirabegron | Mirabegron | Mirabegron | Mirabegron | Tolterodine |
---|---|---|---|---|---|---|
OCAS | OCAS | OCAS | OCAS | ER | ||
25 mgb
| 50 mg | 100 mg | 200 mg | 4 mg | ||
(n = 169) | (n = 169) | (n = 168) | (n = 167) | (n = 85) | ||
Patients, n (%) | ||||||
Overall | 26 (15.4) | 34 (20.1) | 38 (22.5) | 36 (21.4) | 37 (22.2) | 13 (15.3) |
Cardiac disorders | 1 (0.6) | 4 (2.4) | 7 (4.1) | 2 (1.2) | 5 (3.0) | 1 (1.2) |
Eye disorders | 3 (1.8) | 3 (1.8) | 2 (1.2) | 1 (0.6) | 6 (3.6) | 0 (0.0) |
Gastrointestinal disorders | 9 (5.3) | 14 (8.3) | 14 (8.3) | 16 (9.5) | 12 (7.2) | 7 (8.2) |
Constipation | 2 (1.2) | 2 (1.2) | 4 (2.4) | 3 (1.8) | 3 (1.8) | 1 (1.2) |
Dry mouth | 3 (1.8) | 5 (3.0) | 3 (1.8) | 5 (3.0) | 3 (1.8) | 3 (3.5) |
Dyspepsia | 1 (0.6) | 1 (0.6) | 1 (0.6) | 0 (0.0) | 4 (2.4) | 0 (0.0) |
Nausea | 2 (1.2) | 2 (1.2) | 2 (1.2) | 7 (4.2) | 1 (0.6) | 1 (1.2) |
General disorders and administration site conditions | 2 (1.2) | 3 (1.8) | 6 (3.6) | 3 (1.8) | 1 (0.6) | 1 (1.2) |
Investigations | 9 (5.3) | 10 (5.9) | 4 (2.4) | 6 (3.6) | 7 (4.2) | 1 (1.2) |
Gamma-glutamyl transferase increased | 2 (1.2) | 4 (2.4) | 0 (0.0) | 2 (1.2) | 2 (1.2) | 0 (0.0) |
Nervous system disorders | 6 (3.6) | 7 (4.1) | 10 (5.9) | 7 (4.2) | 6 (3.6) | 1 (1.2) |
Dizziness | 1 (0.6) | 0 (0.0) | 6 (3.6) | 2 (1.2) | 0 (0.0) | 0 (0.0) |
Headache | 4 (2.4) | 6 (3.6) | 5 (3.0) | 4 (2.4) | 3 (1.8) | 1 (1.2) |
Psychiatric disorders | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.6) | 1 (0.6) | 2 (2.4) |
Vascular disorders | 4 (2.4) | 4 (2.4) | 4 (2.4) | 6 (3.6) | 2 (1.2) | 0 (0.0) |