Droxidopa Phase II trial for Fibro approved

Pharmaceutical company Chelsea Therapeutics International, Ltd today announced that it has has received approval from the UK's Medicines and Healthcare products Regulatory Agency (MHRA) to begin a Phase II trial of Droxidopa, alone and in combination with carbidopa, for the treatment of Fibromyalgia Syndrome (Fibro).

Low levels of the neurochemical norepinephrine have been the target for finding medications for Fibro for some time. Droxidopa, a synthetic amino acid, is converted by the body into norepinephrine and, as a neutral amino acid, it is able to cross the blood-brain barrier, unlike norepinephrine itself, thus providing both a peripheral and central affect on circulating norepinephrine levels.

To evaluate the role of norepinephrine in Fibro and the safety and efficacy of Droxidopa as a treatment for the condition, Chelsea Therapeutics intends to conduct an exploratory Phase II trial of Droxidopa, both alone and in combination with carbidopa in 120 Fibro patients. Carbidopa is expected to limit how much the Droxidopa is converted into norepinephrine before it reaches the brain, thus promoting a greater central effect in those patients receiving the combination therapy of both medications. In addition to promoting the central effect of Droxidopa, Chelsea Therapeutics hopes that the addition of carbidopa may allow lower doses of Droxidopa to be used thus further reducing the risk of any potential side effects.

Chelsea Therapeutics intends to initiate a multi-centre, randomized, double-blind, placebo-controlled Phase II trial in September. 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: 200mg, 400mg or 600 mg of Droxidopa TID; 25mg or 50mg carbidopa TID; 200/25mg, 400/25mg or 600/25mg Droxidopa/carbidopa TID; 200/50mg, 400/50mg or 600/50mg Droxidopa/carbidopa 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 (FIQ), Patient Global Impression of change (PGI-C), Multidimensional Fatigue Inventory (MFI), and Hamilton Anxiety Depression survey (HAMA). Chelsea Therapeutics expect that results from this trial will be available in 2010.

Dr. Simon Pedder, Chelsea's President and Chief Executive Officer, commented that:

"This approval to begin Phase II clinical trials of both mono- and combination therapy in fibromyalgia is a tremendous step forward in our development of Droxidopa, as it as it enables us to begin our first clinical evaluation of Droxidopa in a new indication outside its existing Japanese label and begin to leverage the full potential of droxidopa in a broad range of indications in which norepinephrine deficiency may play a significant role. Given the established role of norepinephrine in pain attenuation, recent clinical data suggesting the efficacy of SNRIs in treating fibromyalgia and the abundant preclinical data showing dose-dependant analgesia of Droxidopa in chronic pain, we are optimistic about the potential role Droxidopa could play in the multibillion dollar fibromyalgia market."

Chelsea Therapeutics is a biopharmaceutical development company, based in Charlotte, North Carolina, USA, that acquires and develops innovative products for the treatment of a variety of human diseases.