Chelsea Therapeutics International has reported results of a phase II dose-finding study designed to evaluate the safety and determine the potential therapeutic dose range of droxidopa, alone or in combination with carbidopa, that might be effective for the treatment of fibromyalgia.

Topline results of the study indicate a dose response with the highest dose of droxidopa, 600 mg TID, demonstrating a 6.2-point average improvement from a baseline score of 23.00 on the Short Form McGill Questionnaire (SF-MPQ) at the end of the nine-week treatment period, the study's primary endpoint. This reflects a 3.2 unit improvement over placebo on the SF-MPQ total pain score.

Although the study was not designed to demonstrate statistical significance given the limited number of patients per arm, results of the study show a mean change in pain as measured by the visual analog scale (VAS) of -1.64 for patients treated with droxidopa monotherapy compared to a mean change of -0.90 for placebo. Assessment using the Fibromyalgia Index Questionnaire (FIQ) showed patients treated with droxidopa monotherapy demonstrated a mean change from baseline of -9.72 compared to -4.74 reported by patients in the placebo arm. Administration of droxidopa as a monotherapy proved more effective than droxidopa/carbidopa combination therapy in this study.

While overall discontinuations in the study were consistent with the relatively high dropout rates observed in fibromyalgia studies, there were fewer discontinuations in the monotherapy arm (29.2%) compared to placebo (46.7%). No serious adverse events were observed with either droxidopa monotherapy or combination treatment with carbidopa.

The phase II trial, conducted in the U.K., was a multi-center, randomized, double-blind, placebo-controlled, dose response, factorial 12-arm parallel group study evaluating 120 patients equally randomized to receive Droxidopa monotherapy, carbidopa monotherapy, Droxidopa/carbidopa combination therapy or placebo. Following the recommendation of an independent data monitoring committee, in July 2010 the trial was optimized to continue enrollment only in the following seven arms: placebo; 50mg carbidopa TID, 600mg droxidopa TID; 400/25mg, 200/50mg, 400/50mg or 600/50mg droxidopa/carbidopa TID.

The primary endpoint was the average reduction in pain as measured by the Short Form McGill Pain Questionnaire. Secondary outcomes of the study include Fibromyalgia Index Questionnaire (FIQ) and Visual Analog Scale (VAS).