Chelsea Therapeutics International, Ltd (CHARLOTTE, North Carolina), a biopharmaceutical development company, announced that it has received approval from the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) to begin a phase II trial of Droxidopa, as monotherapy and in combination with carbidopa, for the treatment of fibromyalgia. Droxidopa, an orally active synthetic amino acid precursor of norepinephrine (NE), is converted by the body into norepinephrine and as a prodrug of NE, provides replacement therapy for NE deficiency. Although NE, as a catecholamine does not penetrate the blood-brain barrier, Droxidopa, as a neutral amino acid, is able to do so thus providing both a peripheral and central affect on circulating NE levels.

Chelsea intends to conduct an exploratory phase II trial of the drug, both alone and in combination with carbidopa in 120 fibromyalgia patients. As a dopa decarboxylase inhibitor that does not cross the blood-brain barrier, carbidopa is expected to limit the peripheral metabolism of Droxidopa into NE before it crosses into the brain, thus promoting a greater central effect in those patients receiving combination therapy. In addition to promoting the central effect of the drug, the addition of carbidopa may allow lower doses of Droxidopa to be used thus further reducing the risk of any potential side effects.

Chelsea plans to initiate a multicenter, randomized, double-blind, placebo-controlled, dose response, factorial 12-arm parallel group phase II trial in September 2008. The 12-arm trial will evaluate 120 patients equally randomized to receive Droxidopa monotherapy, carbidopa monotherapy, Droxidopa/carbidopa combination therapy or placebo. Accordingly, 10 patients will be randomized into each of 12 groups to receive Droxidopa 200, 400, or 600 mg TID; carbidopa 25 or 50 mg TID; Droxidopa/carbidopa 200/25, 400/25, or 600/25 mg TID; Droxidopa/carbidopa 200/50, 400/50, or 600/50 mg TID; or placebo over a 9-week treatment period. The primary endpoint will be the average reduction in pain as measured by the Short Form McGill Pain Questionnaire. Secondary outcomes of the study include Fibromyalgia Index Questionnaire, Patient Global Impression of change, Multidimensional Fatigue Inventory, and Hamilton Anxiety Depression survey. Results from this trial are expected to be available in 2010.

Originally approved in 1989 for the treatment of frozen gait or dizziness associated with Parkinson's disease and for the treatment of orthostatic hypotension, syncope, or dizziness associated with Shy-Drager’s syndrome and familial amyloidotic polyneuropathy, Dainippon Sumitomo Pharma Co, Ltd expanded marketing approval in 2000 in Japan to include treatment of vertigo, dizziness, and weakness associated with orthostatic hypotension in hemodialysis patients.

Chelsea is also currently developing a library of metabolically inert antifolate compounds engineered to have potent anti-inflammatory and antitumor 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 rheumatoid arthritis and may have further applications for psoriasis, inflammatory bowel disease, and certain cancers.