CHARLOTTE, N.C., Feb. 7, 2008 (PRIME NEWSWIRE) -- Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) announced that it has initiated patient dosing in study 302, the first of two pivotal Phase III trials designed to demonstrate efficacy and support US marketing of approval of Droxidopa in neurogenic orthostatic hypotension (NOH).
Study 302 is a randomized, placebo-controlled, parallel-group, withdrawal-design Phase III study with an initial open-label dose titration and 7 day open-label treatment period, followed by a 14-day double-blind randomized withdrawal period. During the open label dose titration period, all patients will be titrated to maximum therapeutic benefit with up to 600 mg t.i.d. of Droxidopa and must demonstrate both a blood pressure and symptomatic improvement. Patients not responding to treatment during the titration period will be excluded from the trial. Patients demonstrating improvement remain on their respective effective doses of active drug for 1 week. An equal number of patients (N=59) will then continue receiving Droxidopa or be randomized to placebo for two weeks. At the end of the two-week period, patients are evaluated for changes in symptomatic benefit relative to that recorded at randomization.
The primary endpoint will be the relative symptomatic change, as measured by the mean score of Item 1 (dizziness or light-headedness) of the Orthostatic Hypotension Symptom Assessment (OHSA), 14 days following randomization either to continued therapy with Droxidopa or to placebo. The OHSA scale is a validated scale designed to rate symptoms occurring specifically as a result of low blood pressure and uses an 11-point scale (zero to 10), with more severe symptoms scoring higher.
Study 302 is approximately 5 weeks in duration, including the titration period which could be up to 2 weeks depending on dose response. Both pivotal trials (Studies 301 and 302) will evaluate up to 118 patients, for a combined total of up to 236 patients. Chelsea currently expects to activate approximately 35 North American sites and 15 European sites in each study to allow for broad participation from key opinion leaders while simultaneously expediting enrollment.
It is anticipated that both pivotal studies (301 & 302) will be completed by year-end 2008, allowing for a new drug application (NDA) to be filed with the FDA early in 2009. Patients from Study 302 will also be eligible to enter a renewable three-month extension program (Study 303) to supplement existing safety data.
"I am pleased to report that not only have we initiated patient dosing in our Phase III program, but that we have also made substantial progress in identifying and enrolling a significant number of trial sites that will allow us to move forward aggressively with patient recruitment," commented Dr. Simon Pedder, President and CEO of Chelsea. "A key component to our enrollment strategy is to dramatically increase the number of active sites participating in our trials. In the coming weeks, we expect the rate at which we bring sites online to dramatically increase and in turn anticipate a corresponding increase in the rate of patient screening and enrollment into the trial."
About Droxidopa and Symptomatic Neurogenic Orthostatic Hypotension (NOH)
Symptomatic NOH is a neurogenic disorder resulting from a deficient release of norepinephrine, the neurotransmitter used by sympathetic autonomic nerves to send signals to the blood vessels and the heart. This deficiency results in decreased blood pressure when a person assumes a standing position and is characterized by lightheadedness, dizziness, blurred vision and syncope. Droxidopa, an orally active synthetic precursor of norepinephrine, increases the supply of norepinephrine available for delivery to its receptors to improve orthostatic blood pressure and alleviate symptoms of orthostatic hypotension.
Chelsea estimates that nearly 300,000 patients suffer from chronic symptomatic NOH in the U.S. and EU combined. In addition to creating significant health care costs, symptomatic NOH has a dramatic impact on the quality of patient life. Midodrine, currently the only FDA approved treatment for orthostatic hypotension, not only fails to treat the underlying cause of symptomatic NOH but is limited in its use by a pronounced side-effect profile and black box warning for supine hypertension. Given the chronic nature of symptomatic NOH and the proven safety and tolerability of Droxidopa, Chelsea expects that daily oral treatment with Droxidopa should provide a significant improvement in the long-term treatment of symptomatic NOH.
Droxidopa, developed by and licensed from Dainippon Sumitomo Pharma Co., Ltd. (DSP), initially received Japanese approval in 1989 for the treatment of frozen gait and dizziness on standing associated with Parkinson's Disease and for the treatment of orthostatic hypotension, syncope or dizziness on standing associated with Shy-Drager syndrome and Familial Amyloidotic Polyneuropathy. In 2000, Droxidopa received expanded marketing approval to include prevention of vertigo, dizziness and weakness associated with orthostatic hypotension in hemodialysis patients.
About Chelsea Therapeutics
Chelsea Therapeutics is a biopharmaceutical development company that acquires and develops innovative products for the treatment of a variety of human diseases. The Company is currently developing a library of metabolically inert antifolate compounds engineered to have potent anti-inflammatory and anti-tumor activity to treat a range of immunological disorders. Early clinical data suggests that Chelsea's lead antifolate compound, CH-1504, is a safe and effective treatment alternative to methotrexate for RA and may have further applications for psoriasis, IBD and certain cancers. Chelsea's antifolate program is complemented by a strategic partnership with Active Biotech AB for the joint development of a portfolio of therapeutics targeting immune-mediated inflammatory disorders and transplantation. In addition to its autoimmune pipeline, Chelsea is developing Droxidopa, an orally active synthetic precursor of norepinephrine, for the treatment of neurogenic orthostatic hypotension. Currently approved and marketed in Japan, Droxidopa has accumulated over 15 years of proven safety and efficacy, historically generating annual revenues of approximately $50 million in Japan.
This press release contains forward-looking statements regarding future events. These statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include reliance on collaborations and licenses, risks and costs of drug development, regulatory approvals, intellectual property risks, our reliance on our lead drug candidate CH-1504, our history of losses and need to raise more money, competition, market acceptance for our products if any are approved for marketing, reliance on key personnel including specifically Dr. Pedder, management of rapid growth, and the need to acquire or develop additional products.