ATLANTA - Data from a head-to-head clinical study looking at the effects of two prescription medications used to treat overactive bladder (OAB) showed that treatment with Enablex® (darifenacin) did not result in impaired memory function in healthy adults age 60 and older.(1) In contrast, treatment with Ditropan XL®(i) (oxybutynin extended-release or ER), the other medication evaluated in the study, caused significant memory deterioration. Importantly, the individuals receiving oxybutynin ER failed to notice the change in their memory function. These findings were presented today during the 2006 Annual Meeting of the American Urological Association (AUA).
Enablex and Ditropan XL are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. Both therapies are antimuscarinic agents, meaning they act on muscarinic receptors in the body associated with bladder control.
"Beyond balancing efficacy, tolerability and safety, selecting an appropriate overactive bladder treatment requires consideration of possible cognitive effects. These data indicate that Enablex may be a good treatment option for the older population," stated Gary Kay, PhD, Washington Neuropsychological Institute and lead study investigator. "Clinical studies have demonstrated increased sensitivity of older subjects to antimuscarinics, including effects on memory; prompting us to conduct this clinical trial."
These data are analyses of results from a multi-center, randomized, double-blind, placebo-controlled, parallel-group, three-week study involving 150 healthy older adults (male and female ¡Ý60). Results at three weeks suggest that Enablex (15mg) had no significant effect on memory function and was comparable to placebo, as measured by delayed recall accuracy on the Name-Face Association Test (a standardized, computer-administered test in which subjects try to recall the names of 14 people 30 minutes after being introduced to them). This was the primary endpoint for this study. Other standardized memory function tests used in this study evaluated delayed recall of first-last name associations and object locations.
"As the population grows older, the need for safe and effective overactive bladder treatments continues to increase," said Senior Medical Director Anthony DelConte, M.D., Novartis Pharmaceuticals Corporation. "We are pleased this study provides reassurance that Enablex is a viable treatment option for older adults."
About the study
Following a two-week screening period, subjects were randomized (1:1:1 ratio) to receive once-daily treatment in accordance with U.S. prescribing information with oxybutynin ER, Enablex and placebo. Cognitive function was assessed through the Psychologix/CogScreen battery of computerized cognitive function tests performed during clinic visits at baseline and following each week of treatment.
Subjective memory loss was assessed as a tertiary endpoint, using a validated self-reporting instrument, the Memory Assessment Clinics Self Rating Scale (MAC-S). In contrast with the objective memory tests, there was no significant difference between groups in self-rated memory scores, which suggests that changes in memory went unnoticed by subjects.
In this study, the most common adverse events (dry mouth: 26.5% Enablex, 40% oxybutynin ER; constipation: 20.4% Enablex, 4% oxybutynin ER) resulted in low rates of discontinuation.
More on overactive bladder
Overactive bladder, a condition that affects more than 33 million Americans, is caused by the untimely contraction of the bladder muscle.(2) At least 16 percent of the population over the age of 40 suffers from the chronic and troublesome symptoms of overactive bladder.(3) Although prevalence increases with age, the problem affects people of all ages. People with overactive bladder often limit travel, social and even work activities to avoid potentially embarrassing episodes that can occur with this condition.
Abstract 1271: Effects of Enablex and Extended-Release Oxybutynin on Memory in Older Subjects. Gary G. Kay, PhD, May 23, 2006 1:00-4:00 pm EDT
Enablex is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. Enablex is a potent muscarinic receptor antagonist that helps reduce incontinence episodes, increases the amount of urine that the bladder can hold, and decreases the pressure or urgency associated with the urge to urinate. It offers a unique M3 selectivity profile with sustained efficacy and low rates of central nervous system and cardiovascular side effects. Enablex works by preferentially blocking the M3 receptor that is primarily responsible for bladder muscle contraction.
Enablex has been studied in more than 98 clinical trials with a combined total of more than 10,500 people. In clinical trials, the most frequently reported adverse events with Enablex were dry mouth, constipation, dyspepsia and abdominal pain; however, patient discontinuation rates due to these events were low. The majority of adverse events in Enablex-treated subjects were mild or moderate and mostly occurred during the first two weeks of treatment. As with other overactive bladder medications, Enablex is contraindicated in patients with urinary retention, gastric retention or uncontrolled narrow-angle glaucoma and in patients who are at risk for these conditions. Enablex is also contraindicated in patients with known hypersensitivity to the drug or its ingredients.
Novartis Pharmaceuticals Corporation and Procter & Gamble Pharmaceuticals, Inc. (P&GP), a division of The Procter & Gamble Company, are collaborating on the co-promotion and further development of Enablex® (darifenacin) extended release tablets for the treatment of overactive bladder in the United States.
The foregoing release contains forward-looking statements that can be identified by terminology such as "further development," or similar expressions or by express or implied discussions regarding potential new indications or labeling for Enablex or regarding potential future sales of Enablex. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Enablex to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Enablex will be approved for any additional indications or labeling in any market. Nor can there be any guarantee that Enablex sales will reach any particular levels. In particular, management's expectations regarding Enablex could be affected by, among other things, unexpected clinical trial results, including additional analysis of existing clinical data and new clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; increased government , industry, and general public pricing pressures; and other risks and factors referred to in the Novartis AG's current Form 20-F on file with the U.S. Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including those in the cardiovascular, metabolic, cancer, organ transplantation, central nervous system, dermatological, gastrointestinal and respiratory areas. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS) - a world leader in offering medicines to protect health, treat disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. Novartis is the only company with leadership positions in both patented and generic pharmaceuticals. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. In 2005, the Group's businesses achieved net sales of USD 32.2 billion and net income of USD 6.1 billion. Approximately USD 4.8 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 96,000 people and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.
Editor's Note: Full prescribing information available at www.enablex.com.
(i) Ditropan XL is a registered trademark of Alza Corporation, a subsidiary of Johnson & Johnson
(1) Kay, Gary G., et al. "Effects of Darifenacin and Extended-Release Oxybutynin on Memory in Older Subjects" Abstract 1271, American Urological Association Annual Meeting 2006.
(2) Increasing Awareness and Improving the Care of Urinary Incontinence: Highlights from the World Health Organization 2nd International Consultation on Incontinence. Reviews in Urology. 2003; Vol 5, No 1: 22-25.
(3) National Association For Continence. About Incontinence: Urge/OAB. Prevalence. www.nafc.org. [Last accessed, 5/4/06]
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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