Although stress urinary incontinence (SUI) has an unfavorable impact on women’s quality of life, no standard pharmacotherapy is currently available worldwide. TAS-303, a selective oral noradrenaline reuptake inhibitor, is currently under development as an effective and safe treatment for SUI. The primary objective of the present randomized, placebo-controlled, double-blind study was to assess the efficacy of TAS-303 18 mg, as measured by the percent change in SUI episode frequency (SUIEF) per 24 hours, after a 12-week treatment in female patients with SUI compared with placebo. The primary study results showed that the TAS-303 group had significantly improved SUIEF compared to the placebo group, with no safety concerns (as presented at ICS2022). Several subgroup analyses were performed to evaluate the impact of patient characteristics, such as baseline SUI severity and age, on the efficacy of TAS-303.

This study included Japanese female patients with SUI, including stress-predominant mixed urinary incontinence (MUI), aged at least 20 years, with SUI symptoms for at least 12 weeks and positive 1-hour pad test results. In addition, patients with mean SUIEF per 24 hours of ≥ 1 based on a 7-day bladder diary entry proceeded to the treatment period. Randomization was performed using an interactive web-based response system. In this study, after completion of a single-blind observation period of receiving placebo once daily for 3 weeks, patients orally received TAS-303 18 mg or placebo once daily for 12 weeks in the double-blind treatment period. The primary endpoint was the percentage change in the mean SUIEF per 24 h from baseline to week 12. These additional analyses focused on the severity and age of patients with SUI. Subgroup analyses were performed with mean SUIEF ≥ 2 per 24 hours and age ≥ 60 years at baseline. SUI severity was further investigated based on the detailed frequency of SUI episode (mean SUIEF per 24 hours: 1–1.5, 1.5–2, 2–3, 3–4, 4–5, 5 ≤ ). The amount of incontinence measured using the 24-hour pad weight test was also characterized (none: 0–4.4 g, mild: 4.4–20 g, moderate: > 20–75 g, severe: > 75 g).

The full analysis set (FAS) consisted of 231 patients that were randomized (116 and 115 patients in the TAS-303 and placebo groups, respectively). The mean age of the TAS-303 and placebo groups were 53.9 and 54.1 years, respectively. A total of 106 (91.4 %) patients in the TAS-303 group and 107 (93.0 %) in the placebo group were diagnosed with SUI. The mean SUIEF per 24 hours at baseline was 2.009 and 2.126 in the TAS-303 and placebo groups, respectively. The percent change in mean SUIEF per 24 hours at week 12 in the FAS were -58.48 % and -46.70 % in the TAS-303 and placebo groups, respectively (P value=0.022, Student's t-test) (Figure 1). The percent change in mean SUIEF per 24 hours at week 12 from the mean SUIEF ≥ 2 per 24 hours at baseline were -59.28 % and -40.53 % in the TAS-303 and placebo groups, respectively (Figure 2). In the subgroup with the higher baseline SUIEF, the percent change of SUIEF in the TAS-303 group was similar to that of the overall population, but smaller in the placebo group.
The percent change in mean SUIEF per 24 hours at week 12 in per mean SUIEF (1–1.5, 1.5–2, 2–3, 3–4, 4–5, 5 ≤ ) were -59.40 %, -53.19 %, -59.86 %, -59.93 %, -45.87 %, and -73.90 % in the TAS-303 group, respectively, and -47.37 %, -62.64 %, -47.81 %, -46.25 %, -17.93 %, and -7.52 % in the placebo group, respectively. The percent change in mean SUIEF per 24 hours at week 12 in the 24-hour pad test severity (none: 0–4.4 g, mild: 4.4–20 g, moderate: > 20–75 g, severe: > 75 g) were -63.77 %, -55.21 %, -56.08 %, and -81.51 % in the TAS-303 group, and -49.04 %, -49.87 %, -37.02 %, and -20.76 % in the placebo group. A more detailed analysis of SUI severity showed that the TAS-303 group was as effective as the overall population, regardless of severity of SUI. Whereas, the placebo group showed a smaller effect in the severe population.
The percent change in mean SUIEF per 24 hours at week 12 in patients aged ≥ 60 years were -67.46 % and -49.36 % in the TAS-303 and placebo groups, respectively. Compared to the overall population, the difference between the TAS-303 and placebo groups widened in the elderly population.

The efficacy of TAS-303 in improving SUIEF was similar across the entire group and each subgroup. The difference between TAS-303 and the placebo groups appeared to increase in the group with severe symptoms, which could be attributed to the higher placebo effect observed in the mild group.

While treatments such as surgery, bulking agents, and other therapies are currently available for SUI, there is no standard useful pharmacotherapy. TAS-303, an oral medication, is expected to become a treatment option for patients with various SUI severity owing to its convenient administration and favorable balance of efficacy and safety.

Continence 7S1 (2023) 100768
DOI: 10.1016/j.cont.2023.100768