An investigational medication designated TAS-303 shows efficacy and safety in treatment of women with stress urinary incontinence (SUI), reports a placebo-controlled clinical trial in the August issue of The Journal of Urology®, an Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.
"Our study adds new evidence that TAS-303 reduces the frequency of incontinence episodes in women with SUI, without the worrisome adverse effects associated with the existing SUI medication duloxetine," comments Prof. Momokazu Gotoh of Chukyo Hospital, Nagoya, Japan.
A safer medication option for treatment of SUI?
Stress urinary incontinence – defined as leakage on exertion or with sneezing or coughing – is a common clinical problem, particularly in women. Recommended treatments include pelvic floor muscle training (PFMT) and surgery (mid-urethral sling procedure). Currently, medication options for SUI are limited.
Duloxetine – a type of medication called a serotonin and noradrenaline reuptake inhibitor – is approved for treatment of SUI in Europe, but not in the United States or Japan. That reflects concerns about adverse effects, including a risk of nausea causing patients to discontinue treatment. Duloxetine has also been linked to a slightly increased risk of suicide or violence among patients with major depression.
TAS-303 is a different class of medication – a highly selective noradrenaline reuptake inhibitor – that has been shown to increase pressures within the urethra, potentially lessening leakage from the bladder. Because it is highly selective for the peripheral nervous system and does not affect serotonin reuptake, TAS-303 may avoid the adverse effects associated with duloxetine.
TAS-303 reduces SUI episode frequency while avoiding adverse effects
Building on promising results in preliminary studies, the researchers designed a phase 2 clinical trial to evaluate the effectiveness and safety of TAS-303 for SUI. In the study, 231 women with SUI symptoms were randomly assigned to treatment with TAS-303 or inactive placebo pills.
In the primary endpoint, percent change from baseline to week 12 in mean frequency of SUI episodes per 24 hours, patients assigned to TAS-303 had a significant reduction. On analysis accounting for other patient characteristics (least squares mean), the frequency of SUI episodes decreased by about 58% with TAS-303, compared to 47% in the placebo group. Frequency of SUI episodes decreased by at least half in 65% of patients in the TAS-303 group versus 53% with placebo.
The reduction in episode frequency with TAS-303 "was more clearly confirmed" in patients with more severe SUI (two or more episodes per day). The improvement also appeared greater in patients aged 60 years or older.
Benefits appeared within four weeks of treatment and continued through at least 12 weeks. The researchers suggest that combining TAS-303 with PMFT might allow for more rapid improvement – thus encouraging patients to continue PMFT exercises, which may take up to 12 weeks to show an effect. TAS-303 also showed improvement in urinary incontinence amount and health-related quality of life.
"Based on these findings, TAS-303 may be considered to have comparable efficacy with that of duloxetine and improved safety due to the absence of nervous system- or gastrointestinal-related adverse drug reactions," Dr. Gotoh and coauthors conclude. They emphasize that further studies in more diverse patient samples will be needed to confirm the effectiveness of TAS-303 for SUI.
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