Study To Assess The Clinical Benefit Of Droxidopa And Droxidopa/Carbidopa In Subjects With Fibromyalgia

Fibromyalgia syndrome (FMS) and Chronic widespread pain (CWP) are two syndromes within a broader class known as functional somatic syndromes. Chronic widespread pain (CWP) is defined according to the American College of Rheumatology (ACR), as pain both above and below the waist involving both sides of the body and lasting for at least 3 months. Fibromyalgia syndrome (FMS), a subset of CWP, is a multisystem disease characterized by sleep disturbance, fatigue, headache, morning stiffness, paresthesias, and anxiety.

While there is debate as to specific etiology and pathogenesis, fibromyalgia is generally believed to be the result of a perturbation of central pain processing, specifically the neuroendocrine system. Fibromyalgia patients have been shown to have lower levels of metabolites from three neurotransmitters (serotonin, norepinephrine, and dopamine) in their cerebrospinal fluid (CSF) compared to healthy controls. The low rate of turnover of these neurotransmitters supports the hypothesis of a metabolic defect in fibromyalgia and suggests that the defect occurs at a neuroregulatory level. Results of a study that examined the effect of a permanent reduction in the noradrenergic innervation of the spinal cord suggested that the antinociceptive effects of norepinephrine are closely linked to opioidergic and tachykinergic neurotransmission.

Droxidopa \[also, known as L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS, or L-DOPS\] is the International non-proprietary name (INN) for a synthetic amino acid precursor of norepinephrine (NE), which was originally developed by Sumitomo Pharmaceuticals Co., Limited, Japan. It has been approved for use in Japan since 1989. Droxidopa has been shown to improve symptoms of orthostatic hypotension that result from a variety of conditions including Shy Drager syndrome (Multiple System Atrophy), Pure Autonomic Failure, and Parkinson's disease. There are four stereoisomers of DOPS; however, only the L-threo-enantiomer (droxidopa) is biologically active. Data from clinical studies and post-marketing surveillance programs conducted in Japan show that the most commonly reported adverse drug reactions with droxidopa are increased blood pressure, nausea, and headache. In clinical studies to date, data suggests that droxidopa is well-tolerated and effective as a norepinephrine precursor.

Pre-clinical and clinical studies suggest that droxidopa has an analgesic effect in patients with chronic pain. An increase in central nervous system (CNS) levels of norepinephrine has been shown to correlate with an analgesic effect. Based on the pre-clinical and clinical findings to date, it is hypothesized that droxidopa can provide pain reduction in fibromyalgia patients through increasing the CNS levels of norepinephrine.