MENLO PARK, Calif., Oct. 3, 2012 /PRNewswire/ -- Depomed, Inc. (NASDAQ: DEPO) announced today that it is presenting two abstracts from its Phase 3 clinical trial, BREEZE 3, at this week's 23rd Annual Meeting of the North American Menopause Society (NAMS) in Orlando, FL. The data showed that Serada®, Depomed's investigational non-hormonal extended-release formulation of gabapentin, may help manage menopausal hot flashes.
"Hot flashes are a disruptive problem affecting as many as three out of four menopausal women," said JoAnn V. Pinkerton, M.D., principal investigator of BREEZE 3 and Medical Director of Midlife Health Center, Professor of Obstetrics and Gynecology and Vice Chair of Academic Affairs at the University of Virginia, Charlottesville. "At this time, hormone therapy is the only approved treatment for hot flashes, yet about 40% of symptomatic women either choose not to go on hormones or are not good candidates. The BREEZE data findings are important news for women who are looking for more choices to manage their hot flashes and the sleep issues that often accompany them."
BREEZE 3 Statistical Analyses - Non-parametric Analysis vs. ANCOVA Parametric Analysis. The BREEZE 3 study included 600 menopausal women who were treated with either Serada 1800mg daily (given as one 600mg tablet in the morning and two 600mg tablets at night) or placebo for 24 weeks. Depomed entered into a Special Protocol Assessment with the FDA with respect to the BREEZE 3 study that specified Depomed would use a non-parametric analysis for the efficacy data from BREEZE 3, and would also perform a supportive parametric ANCOVA statistical analysis. As previously disclosed, based on the primary non-parametric analysis, efficacy data from the trial were positive and statistically significant for three of the four pre-specified primary endpoints of frequency and severity of hot flashes at four and 12 weeks. Data for the key secondary endpoints of frequency and severity at 24 weeks did not achieve statistical significance.
The results of the supportive ANCOVA parametric analysis of the BREEZE 3 data were presented at NAMS. In this analysis, Serada significantly reduced the frequency and severity of hot flashes at 4 weeks and 12 weeks compared with placebo. These reductions were maintained out to 24 weeks. In addition, an assessment of sleep measures taken at the start of the trial indicated that, on average, women had clinically meaningful improvements in insomnia and sleep disturbance.
Jim Schoeneck, President and CEO of Depomed, noted, "The Breeze 3 study builds on the positive trends we saw in the earlier Breeze 1 and 2 trials. We believe Serada has the potential to be the first non-hormonal and non-antidepressant therapy for hot flashes."
Depomed submitted an NDA for Serada to the FDA at the end of July 2012.
Phase 3 Trial Results
The first abstract reports the final results of BREEZE 3 using the supportive ANCOVA parametric analysis, which found that Serada helped women manage their hot flashes symptoms. Specifically, the trial showed:
- Serada significantly reduced the average frequency of hot flashes at 4 weeks (-1.69 vs. placebo, p<0.0001) and at 12 weeks (-1.14 vs. placebo, p=0.0007), compared with placebo
- Serada significantly reduced the average severity of hot flashes at 4 weeks (-0.21 vs. placebo, p<0.0001) and at 12 weeks (-0.19 vs. placebo, p=0.0102)
- Reductions were maintained out to 24 weeks (frequency: -1.08 vs. placebo, p=0.0174; severity: -0.22 vs. placebo, p=0.0457)
- Significantly more women said their symptoms improved with Serada at 12 weeks (68% vs. 54% with placebo; p<0.0036) and 24 weeks (74% vs. 54% with placebo; p<0.0001)
Using the non-parametric statistical analysis, the trial results for the co-primary endpoints were statistically significant for the reduction in average frequency of hot flashes at 4 weeks (p=0.0003), the reduction in the average severity of hot flashes at 4 weeks (p<0.0001) and 12 weeks (p=0.0102), but were not statistically significant for the reduction in average frequency of hot flashes at 12 weeks (p=0.10). The results were not statistically significant at 24 weeks for the reduction of hot flash frequency (p=0.2351) or severity (p=0.1510).
Overall, Serada was well tolerated. Five percent more patients on Serada than placebo withdrew from the trial due to adverse events (16.7% vs. 11.5%, respectively). The most common adverse events were headache (9% vs. 8% placebo), daytime sleepiness, or somnolence (6% vs. 3% placebo), upper respiratory tract infections (6% vs. 4% placebo), and dizziness (13% vs. 3% placebo), which are the most bothersome side effects commonly associated with gabapentin. Of note, both treatment arms reported minimal changes in weight over the 24-week arm
Impact of Serada on Sleep The second abstract assessed the impact of Serada on two measures of sleep – the Insomnia Severity Index (ISI) Score and the daily sleep interference (S/I) score. At baseline, women had an ISI Score of >17 indicating moderate insomnia (17.54, Serada and 17.33, placebo) and an S/I score of >7 indicating moderate-to-severe sleep disturbance (7.3, Serada and 7.4, placebo).
After 12 weeks of treatment, Serada produced clinically meaningful improvement in ISI scores (-8.7 vs. -6.3 placebo, p=0.0044) and in S/I scores (-3.6 vs. -2.8 placebo, p=0.0056). These reductions were maintained throughout week 24: ISI score change of -8.6 vs. -6.2 placebo, p=0.0056; and S/I score change of -3.9 vs. -3.0 placebo, p=0.0084).
"Hot flashes can impact many aspects of a woman's quality of life, especially her ability to sleep. In fact, insomnia typically worsens with the severity of hot flashes," said Risa Kagan, M.D., lead investigator of the sleep study at the Jordan Research and Education Institute (REDI) at Alta Bates Summit Medical Center and Clinical Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco. "The data from the Breeze 3 trial may allow us to offer more options for our patients suffering from hot flashes and who have difficulty sleeping."
Breeze 3 Trial Design Breeze 3 is a randomized, double-blind, placebo-controlled study of approximately 600 post-menopausal women experiencing 7 or more moderate-to-severe hot flashes each day. Patients were randomized into one of two treatment arms, with patients receiving either placebo or a total dose of 1800mg of Serada dosed as 600mg in the morning and 1200mg in the evening. The co-primary efficacy endpoints in the study were reductions in the mean frequency of moderate-to-severe hot flashes, and the average severity of hot flashes, measured after four and 12 weeks of stable treatment.
About Menopausal Hot Flashes Hot flashes, which affect 32 million women in the U.S. annually, are characterized by a sudden, temporary onset of body warmth, flushing and sweating. Hot flashes are disruptive and can impact women's overall quality life, affecting their mood and their ability to sleep. In fact, insomnia typically worsens with the severity of hot flashes. According to the North American Menopause Society, hot flashes are the most common menopause-related source of discomfort. Research suggests hot flashes occur when the body's internal thermoregulatory mechanism -- located in the hypothalamus -- becomes irregular, narrowing the body's thermoneutral zone. Thus, even small fluctuations in body temperature can cause menopausal women to experience profuse sweating or severe chills that would not affect a person with a properly functioning thermoregulatory mechanism.
About Serada Serada is a non-hormonal, non-antidepressant investigational treatment for hot flashes that involves an extended-release formulation of gabapentin in combination with Depomed's proprietary Acuform® drug delivery technology. By combining gabapentin with the Acuform technology, Serada is absorbed slowly into the upper gastrointestinal tract over several hours rather than immediately to ensure a steady release of medication and to help reduce potential side effects. Serada is not approved to treat any condition.
About Depomed Depomed, Inc. is a specialty pharmaceutical company with three approved and marketed products. Gralise® (gabapentin) is a once-daily treatment approved for the management of postherpetic neuralgia (PHN). Zipsor® (diclofenac potassium) Liquid Filled Capsules is a non-steroidal anti-inflammatory drug (NSAID) indicated for relief of mild to moderate acute pain in adults. Glumetza® (metformin hydrochloride extended release tablets) is approved for use in adults with type 2 diabetes and is commercialized by Santarus, Inc. in the United States. Depomed formulates its products and product candidates with its proven, proprietary Acuform® drug delivery technology, which is designed to improve existing oral medications, allowing for extended release of medications to the upper gastrointestinal tract when dosed with food. Additional information about Depomed may be found on its website, www.depomed.com.
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