Depomed, Inc. announced that it has reached agreement with the US Food and Drug Administration (FDA) regarding a Special Protocol Assessment (SPA) on the design and analysis of Breeze 3, a phase 3 trial evaluating Serada (extended release gabapentin tablets) for menopausal hot flashes.
Depomed is initiating Breeze 3 immediately as clinical sites are all on line with more than 200 patients in the screening process already. Breeze 3 is expected to be completed by the end of the third quarter of 2011, with results to be reported in the fourth quarter.
"We believe that Breeze 3 will be successful based on the new refined trial design which is expected to accurately measure Serada's drug effect, and result in a placebo effect between 45 per cent to 55 per cent, as seen in other published hot flash trials," said Michael Sweeney, M.D., Depomed's vice president, research and development.
Carl A. Pelzel, president and chief executive officer of Depomed, added, "We are pleased to reach an SPA agreement with the FDA, and advance this important product candidate closer to commercialization."
Breeze 3 will be a randomized, double-blind, placebo-controlled study of approximately 600 patients. Patients will be randomized into one of two treatment arms, with patients receiving either placebo or a total dose of 1800mg of Serada dosed 600mg in the morning and 1200mg in the evening. The co-primary efficacy endpoints in the study will be 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. As in the prior Breeze 1 trial, the treatment duration of the study will be 24 weeks, to address the FDA's view that an effective drug should also demonstrate persistence of efficacy at 24 weeks.
Modifications to the design of Breeze 3 relative to Breeze 1 and 2 include: (i) a single active arm rather than two arms, and therefore a required statistical p value of .05 rather than .025 to achieve statistical significance; (ii) 65 per cent more patients in the active treatment arm than in Breeze 1 and 2; (iii) a two-week run in period to prior to randomization, rather than one week, which is designed to reduce the regression to the mean observed in Breeze 1 and 2, resulting in a more stable baseline, and thereby potentially reducing the placebo effect; and (iv) an alternative statistical analysis method, known as a non-parametric analysis, that is designed to reduce the influence significant outliers can have on the achievement of efficacy endpoints.
An SPA is an agreement with the FDA that a proposed trial protocol design, clinical endpoints and statistical analyses are acceptable to support a product candidate's regulatory approval.
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 impact women's overall quality of 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 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 perfuse sweating or severe chills that would not affect a person with a properly functioning thermoregulatory mechanism.
Serada is an extended-release formulation of gabapentin for the treatment of menopausal hot flashes using Depomed's proprietary Acuform drug delivery technology. By combining gabapentin with Acuform technology, Serada is absorbed slowly into the upper gastrointestinal tract over several hours rather than immediately. Immediate release formulations of gabapentin have been approved by the FDA to treat neuropathic pain and epilepsy.
Depomed, Inc. is a specialty pharmaceutical company with one product candidate through Phase 3 clinical development, another in phase 3 clinical development, two approved products on the market and other product candidates in its early stage pipeline.