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Clinical Trial
. 2021 Mar;32(3):673-680.
doi: 10.1007/s00192-020-04470-7. Epub 2020 Oct 10.

TAS-303 effects on urethral sphincter function in women with stress urinary incontinence: phase I study

Makoto Yono  1   2 , Shin Irie  3   4 , Momokazu Gotoh  5   6
Affiliations
Clinical Trial

TAS-303 effects on urethral sphincter function in women with stress urinary incontinence: phase I study

Makoto Yono et al. Int Urogynecol J. 2021 Mar.

Abstract

Introduction and hypothesis: TAS-303, which selectively inhibits noradrenaline reuptake, was developed for treating stress urinary incontinence (SUI). The proximal urethra mainly comprises smooth muscle fibers in which α1 adrenergic receptors are abundant. This study was conducted to evaluate the effect of TAS-303 on urethral function and its safety profile in female patients with SUI.

Methods: In total, 16 women (age, 20-64 years) with SUI and > 5.0 g of leakage in the 1-h pad test at screening were randomized and administered the assigned treatment in a double-blind manner. The primary end point was change in the maximal urethral closure pressure (MUCP) at 6 h post-dose. The secondary end point was change in the urethral closure pressure of the entire urethra and each urethral region (proximal, middle, and distal) at 6 h post-dose. The results were analyzed using a t-test.

Results: The mean change ± standard deviation in MUCP at 6 h post-dose was 3.473 ± 12.154 cmH2O for TAS-303 and 2.615 ± 9.794 cmH2O for placebo (between-group difference: 0.858 cmH2O, P = 0.8047). The mean changes ± standard deviation in urethral closure pressure of the proximal urethra at 6 h after the administration of TAS-303 18 mg and placebo were 3.863 ± 10.941 and 1.634 ± 12.093, respectively (between-group difference: 2.229 cmH2O, P = 0.5976).

Conclusions: No significant difference in MUCP and urethral closure pressure was found between TAS-303 and placebo. However, the change in the proximal urethral closure pressure with TAS-303 was larger than that with placebo. This suggests that TAS-303 has pharmacological effects on urethral sphincteric function.

Keywords: Japan; Maximum urethral closure pressure; Randomized controlled study; Stress urinary incontinence; TAS-303; Urethral pressure profile parameters.

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Conflict of interest statement

MG declares having received consultancy fees from Taiho, Astellas, Kowa, and Kyorin and grants from Taiho, Pfizer, Astellas, Daiichi Sankyo, Nihon Kayaku, Nippon Shinyaku, Takeda, and Asahikasei Pharma. All remaining authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Disposition of patients with SUI
Fig. 2
Fig. 2
Maximum urethral closure pressure at rest for the entire urethra (a) and for the proximal (b), middle (c), and distal urethral region (d) before and after administration of TAS-303 18 mg (n = 16) or placebo (n = 16)
Fig. 3
Fig. 3
Mean urethral closure pressure at rest for the entire urethra (a) and for the proximal (b), middle (c), and distal urethral region (d) before and after administration of TAS-303 18 mg (n = 16) or placebo (n = 16)
Fig. 4
Fig. 4
Mean plasma concentration-time profile of TAS-303 in women with stress urinary incontinence (semi-logarithmic scale) after administration of TAS-303 18 mg. N = 16, arithmetic mean ± standard deviation
See this image and copyright information in PMC

References

    1. The International Continence Society (ICS) glossary of terminology. https://www.ics.org/glossary/symptom/stressurinaryincontinence. Accessed 24 Dec 2019.
    1. Fusco F, Abdel-Fattah M, Chapple CR, Creta M, La Falce S, Waltregny D, Novara G. Updated systematic review and meta-analysis of the comparative data on colposuspensions, pubovaginal slings, and midurethral Tapes in the surgical treatment of female stress urinary incontinence. Eur Urol. 2017;72:567–591. doi: 10.1016/j.eururo.2017.04.026. - DOI - PubMed
    1. van der Vaart CH, de Leeuw JR, Roovers JP, Heintz AP. The effect of urinary incontinence and overactive bladder symptoms on quality of life in young women. BJU Int. 2002;90:544–549. doi: 10.1046/j.1464-410X.2002.02963.x. - DOI - PubMed
    1. Coyne KS, Zhou Z, Thompson C, Versi E. The impact on health-related quality of life of stress, urge and mixed urinary incontinence. BJU Int. 2003;92:731–735. doi: 10.1046/j.1464-410X.2003.04463.x. - DOI - PubMed
    1. Thüroff JW, Abrams P, Andersson KE, Artibani W, Chapple CR, Drake MJ, Hampel C, Neisius A, Schröder A, Tubaro A. EAU guidelines on urinary incontinence. Eur Urol. 2011;59:387–400. doi: 10.1016/j.eururo.2010.11.021. - DOI - PubMed

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