A total of 538 patients with OAB were screened, of whom 357 were randomised and 354 were treated. The efficacy analysis included all randomised patients who had efficacy data available from the baseline and at least one on-treatment visit (329 patients). In all, 61 patients (17.1%) discontinued the study before completion; this was because of AEs for 14 patients (3.9%), withdrawal of consent for 34 patients (9.5%) and other reasons for 13 patients (3.7%). A total of 81.7% of patients in the SOL5 group, 82.4% in the SOL10 group and 84.8% in the TOL4 group had their final (end-point) efficacy evaluation at week 12 ().
Baseline characteristics and demographics were similar among all treatment groups as shown in . The mean age of all patients was 52.65–53.07 years. Of all patients, 24.32–30.36% had received previous drug treatment for OAB and 42.06–52.25% reported urgency incontinence. At baseline, there were no differences in voiding parameters among the three groups (p > 0.05).
Patient demographics at baseline
shows the mean changes in all efficacy variables from baseline to end-point in the three groups. After the 12-week treatment, these parameters improved. The improvement rate was the greatest in the SOL10 group, followed by the SOL5 and TOL4 groups (). A non-inferiority test showed that the lower limit of the 95% confidence interval was −0.25, exceeding the limit of non-inferiority of −1. It showed that SOL10 was not inferior to TOL4, so the second step analysis was performed to compare SOL5 and TOL4. This showed that the lower limit of the 95% confidence interval was −0.49, exceeding the limit of non-inferiority of −1. Therefore, we also showed that SOL5 was non-inferior to TOL4.
The mean changes in efficacy variables with solifenacin and tolterodine from baseline to end-point
(A) Changes in the mean daily micturition frequency. (B) The mean micturition volume per voiding (ml). (C) The mean daily urgency incontinence frequency. (D) The mean daily number of urgency episodes. (E) The mean number of nocturia episodes
The SOL10 group had a significantly increased micturition volume per voiding compared with TOL4 group (p = 0.04). Urgency incontinence episodes dramatically decreased in SOL10 group at visit 3 (4 week) compared with other groups although there was no statistical significance at end-point.
Subgroup analysis showed that in patients with dry OAB, the changes in mean daily micturition frequency from baseline were −2.92 in the SOL10 group and −1.85 in the TOL4 group (p = 0.019). In male patients with wet OAB, the changes in mean daily urgency incontinence frequency from baseline were −2.92 in the SOL10 group and −1.85 in the TOL4 group (p = 0.037).
Quality of life improved in all three groups using the King’s Health Questionnaire. But both solifenacin treatments (10 and 5 mg) produced greater improvements from baseline compared with TOL4, although these results were not statistically significant ().
Changes in the quality of life, as assessed by the King’s Health Questionnaire (ANOVA)
The discontinuation rates because of AEs were low and were similar for the three treatment arms. The percentages of patients discontinuing treatment owing to an AE were 4.24% (5/118), 5.93% (7/118) and 1.69% (2/118) in the SOL5, SOL10 and TOL4 groups, respectively (p = 0.28). The incidences of AEs (≥ 2%) after medication are listed in . Among the treatment groups, the incidence of the most common AE, dry mouth, was lowest in the SOL5 group (7.63%, compared with 19.49% and 18.64% in the SOL10 and TOL4 groups, respectively; p = 0.01). Constipation, which was mainly mild or moderate in all groups, was reported in 6.78%, 14.41%, 2.54% of patients in the SOL5, SOL10 and TOL4 groups, respectively (p = 0.003). The incidence of constipation was not statistically different between SOL5 and TOL4 group (p = 0.215) but different between SOL10 and TOL4 group (p = 0.002). Blurred vision (mild in most cases) was reported in 13.56%, 16.95% and 10.17% of patients in the SOL5, SOL10 and TOL4 groups, respectively (p = 0.335).
Incidence rates of adverse events after medication
There were no clinically relevant changes in vital signs, physical examination findings, laboratory values or electrocardiogram results. PVR volumes increased in all groups but they were not clinically significant (). There were no differences of PVR according to the treatment groups and gender (p = 0.826, 0.227), although male patients had more increased PVR than female.
The mean changes in postvoid residual urine volume from baseline to end-point