The impact of patient characteristics on the efficacy of TAS-303 for stress urinary incontinence: sub-group analyses of a phase 2 study

Yokoyama O1, Takahashi S2, Kato K3, Takei M4, Gotoh M5

Research Type

Clinical

Abstract Category

Female Stress Urinary Incontinence (SUI)

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Abstract 50
Female Stress Urinary Incontinence
Scientific Podium Short Oral Session 8
Wednesday 27th September 2023
15:42 - 15:50
Theatre 102
Stress Urinary Incontinence Voiding Diary Pad Test Clinical Trial Prospective Study
1. Department of Urology, Harue Hospital, 2. Department of Urology, Nihon University School of Medicine, 3. Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, 4. Department of Urology, Harasanshin Hospital, 5. Japan Community Health Care Organization Chukyo Hospital
Presenter
O

Osamu Yokoyama

Links

Abstract

Hypothesis / aims of study
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.
Study design, materials and methods
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).
Results
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.
Interpretation of results
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.
Concluding message
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.
Figure 1 The percent change in mean SUIEF per 24 hours at week 12 in the FAS
Figure 2 The percent change in mean SUIEF per 24 hours at week 12 from the mean SUIEF ≥2 per 24 hours at baseline
Disclosures
Funding All authors declare having received consultancy fees from TAIHO Pharmaceutical Co., Ltd. This study was funded by TAIHO Pharmaceutical Co., Ltd. Clinical Trial Yes Registration Number ClinicalTrials.gov Identifier: NCT04512053 RCT Yes Subjects Human Ethics Committee This study was firstly approved by the institutional review board at Nakameguro Atlas Clinic in Tokyo, Japan. Helsinki Yes Informed Consent Yes
Citation

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

14/02/2024 16:04:16