Chelsea reports new Ph III droxidopa data

US drug developer Chelsea Therapeutics presented data from the open-label titration portion of a Phase III trial demonstrating patients treated with droxidopa, a synthetic precursor to norepinephrine, showed a robust reduction in the severity of symptoms associated with neurogenic orthostatic hypotension and a significant improvement standing systolic blood pressure at an international symposium of the American Autonomic Society, held in Hawaii.

Patients identified as responders during the open-label titration phase of the study, and therefore eligible for inclusion in the double-blind, randomized trial, demonstrated a mean improvement of 4.6 units on Item One (dizziness or light-headedness) of the orthostatic hypotension symptom assessment scale during titration. The average baseline score for responders prior to treatment was 6.4 and the average score at the end of the titration was 1.8. OHSA 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. The same measure will be used as the primary endpoint in the blinded study to determine the relative difference in symptomatic benefit between droxidopa and placebo 14 days post-randomization. The study, evaluating up to 118 patients, is powered to detect a mean relative change of 1.6 units or greater between treatment and placebo groups with a standard deviation of three.

In addition to significant symptomatic improvement, says the firm, responders demonstrated a mean improvement in standing systolic blood pressure of 27mmHg. This improvement was achieved with only a modest impact on supine blood pressure, with mean standing SBP increasing 32.4% compared to only a 13.8% rise in mean supine SBP.