Once daily Solifenacin Succinate significantly reduced urgency episodes for patients with overactive bladder

Main Category: Public Health
Article Date: 31 Jul 2004 - 0:00 PDT


Solifenacin succinate appears to be the first antimuscarinic agent to show statistically significant reductions in episodes of urgency across multiple trials

Solifenacin succinate, a once-daily oral antimuscarinic agent in development for the treatment of overactive bladder (OAB), significantly reduced urgency episodes in a pooled analysis of four pivotal trials involving more than 2800 patients, according to data presented today at the annual meeting of the American Urogynecologic Society (AUGS). OAB is a condition that affects approximately 17 million men and women in the United States.

According to the definition of OAB by the International Continence Society, the defining symptom of OAB is urgency, or the sudden, compelling desire to urinate that is difficult to defer. From this data, solifenacin appears to be the first antimuscarinic agent

to show statistically significant reductions in episodes of urgency across multiple trials. "The constant urgent need to urinate can have a debilitating effect on patients," said Vincent Lucente, MD, Chief Medical Officer at the Institute for Female Pelvic Medicine & Reconstructive Surgery. "It can affect the emotional and practical aspects of everyday life - such as being able to sit through an important meeting at work or getting a good night's sleep."

The study results showed patients taking solifenacin 5 mg once-daily experienced 2.9 fewer urgency episodes per 24 hours and patients taking solifenacin 10 mg once-daily experienced 3.4 fewer episodes per 24 hours, compared with those taking placebo who experienced 2.0 fewer episodes per 24 hours (P<0.001 for both doses). Patients reported a mean of approximately six urgency episodes per 24 hours at the time they entered the study.3

"Urgency is one of the defining symptoms of OAB," said Steven Swift, MD, Associate Professor of Benign Gynecology at the Medical University of South Carolina in Charleston, SC. "That's why reducing the number of daily 'urgency episodes' is an important therapeutic goal for both healthcare professionals and patients."

About the studies 3,4

The four pivotal, randomized, double-blind, placebo-controlled, 12-week studies, involving more than 2800 patients, had similar protocols, which permitted pooling of the results for the analysis. Patients evaluable for the efficacy analysis included 1124 treated with placebo, 548 treated with solifenacin 5 mg once-daily, and 1151 treated with solifenacin 10 mg once-daily.

Results included the following:

-- At the end of the study, 62 percent of patients receiving the once-daily dose of solifenacin 5 mg and 66 percent of patients receiving the once-daily dose of 10 mg reported that the number of urgency episodes was reduced by at least 50 percent, compared to only 44 percent of patients receiving placebo.

-- Median percent reductions in urgency episodes from baseline were 66 percent for 5 mg once-daily and 70 percent for 10 mg once-daily, compared with 40 percent for placebo (P<0.001 for both dosage groups vs. placebo).

-- Twenty-nine percent of patients receiving solifenacin 5 mg once-daily and 26 percent of patients receiving solifenacin 10 mg once-daily reported no symptomatic urgency at the study endpoint, compared to 16 percent of patients receiving placebo (P<0.001 for both dosage groups vs. placebo).

A subset analysis revealed that solifenacin was effective in reducing urgency episodes in both women and men.

Solifenacin was well-tolerated in placebo-controlled trials; side effects were predominantly mild or moderate in severity and included dry mouth, constipation and blurred vision. Approximately 11 percent of patients taking solifenacin 5 mg once-daily experienced dry mouth, compared with 28 percent of patients taking solifenacin 10 mg once-daily and 4.2 percent of patients taking placebo. Only 2.8 percent of the patients taking solifenacin 5 mg once-daily and 6.8 percent of patients taking solifenacin 10 mg once-daily discontinued treatment due to an adverse event, compared to 4.4 percent of patients taking placebo.

About Overactive Bladder

Overactive bladder (OAB) is a common bladder control problem affecting more than 17 million Americans and between 50 and 100 million people worldwide. In the past, most studies underestimated the prevalence of OAB because they focused on only those patients with incontinence, and not the more common symptoms of frequency and urgency. As a result, recent studies have suggested that the prevalence of OAB may actually be higher.1

Frequently, sufferers do not seek medical care because they believe - inaccurately - that their symptoms are part of the normal aging process. Patients often are too embarrassed or are reluctant to talk with their physician about bladder control problems. Indeed, 40 percent of affected patients do not seek medical attention, and nearly 75 percent remain untreated.5

About Solifenacin Succinate

Solifenacin succinate is a once-daily oral muscarinic antagonist in development for the treatment of overactive bladder that acts to block the receptors in the smooth muscle of the bladder. The compound was discovered and developed by Yamanouchi Pharmaceuticals and its New Drug Application (NDA) was submitted to the U.S. Food and Drug Administration by Yamanouchi Pharma America in December of 2002. In August of 2003, Yamanouchi and GlaxoSmithKline signed an agreement for the co-promotion of solifenacin in the United States, and both are collaborating to help ensure an expeditious and efficient launch of solifenacin in the US market.

About Yamanouchi Pharmaceutical Co., Ltd.

Yamanouchi Pharmaceutical Co., Ltd., established in 1923 and headquartered in Tokyo, Japan, is a leading pharmaceutical company in Japan. With its subsidiaries worldwide, Yamanouchi is expanding its business base to Europe, the United States and Asia and employs approximately 9,300 people worldwide. The company has discovered and developed many medicines now marketed in the United States through successful licensing agreements. For detailed company information, visit http://www.yamanouchi.com.

About GlaxoSmithKline

GlaxoSmithKline, one of the world's leading research-based pharmaceutical and healthcare companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information, please visit the company's Web site at http://www.gsk.com

i Nitti VW. Clinical impact of overactive bladder. Reviews in Urology. 2002;4(4):S2-S6.

ii Abrams P, Cardozo L, Fall M, et al. The standardisation in terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourology & Urodynamics. 2002;21(2):167-78.

iii Lucente V, Swift S, for YM-905 Study Group. Urgency episodes were significantly reduced with solifenacin treatment for overactive bladder. Abstract presented at: AUGS/SGS Joint Scientific Meeting; July 29-31, 2004; San Diego, Ca.

4 Lucente V, Swift S, for YM-905 Study Group. Urgency episodes were statistically significantly reduced with solifenacin in patients with overactive bladder. Poster presented at: AUGS/SGS Joint Scientific Meeting; July 29-31, 2004; San Diego, Ca.

5 Milsom I, Abrams P, Cardozo L, Roberts RG, Thuroff J, Wein AJ. How widespread are the symptoms of an overactive bladder and how are they managed? a population-based prevalence study. BJU International. 2001;87:760-766.

CONTACT
Emily Voelker
Edelman
(212) 819-4856
Joe Duraes
Edelman
(212) 704-8244

• Additional
• References
• Citations