Droxidopa and Reduced Falls in a Trial of Parkinson Disease Patients With Neurogenic Orthostatic Hypotension.

Objectives: Droxidopa is a prodrug of norepinephrine indicated for the treatment of orthostatic dizziness, lightheadedness, or the "feeling that you are about to black out" in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure including Parkinson disease (PD). The objective of this study was to compare fall rates in PD patients with symptomatic neurogenic orthostatic hypotension randomized to droxidopa or placebo.
Methods: Study NOH306 was a 10-week, phase 3, randomized, placebo-controlled, double-blind trial of droxidopa in PD patients with symptomatic neurogenic orthostatic hypotension that included assessments of falls as a key secondary end point. In this report, the principal analysis consisted of a comparison of the rate of patient-reported falls from randomization to end of study in droxidopa versus placebo groups.
Results: A total of 225 patients were randomized; 222 patients were included in the safety analyses, and 197 patients provided efficacy data and were included in the falls analyses. The 92 droxidopa patients reported 308 falls, and the 105 placebo patients reported 908 falls. In the droxidopa group, the fall rate was 0.4 falls per patient-week; in the placebo group, the rate was 1.05 falls per patient-week (prespecified Wilcoxon rank sum P = 0.704; post hoc Poisson-inverse Gaussian test P = 0.014), yielding a relative risk reduction of 77% using the Poisson-inverse Gaussian model. Fall-related injuries occurred in 16.7% of droxidopa-treated patients and 26.9% of placebo-treated patients.
Conclusions: Treatment with droxidopa appears to reduce falls in PD patients with symptomatic neurogenic orthostatic hypotension, but this finding must be confirmed.
Competing Interests: and Source of Funding: The trial and post hoc analyses were funded by Lundbeck. R.A.H. has received honoraria or payments for consulting, advisory services, or speaking services from Chelsea Therapeutics (now Lundbeck NA Ltd) and Lundbeck. L.A.H. is an employee of Lundbeck. G.J.R. was an employee of Lundbeck at the time of the studies and manuscript development. S.H. has provided consulting services to Lundbeck NA Ltd. S.H.I. has received honoraria in the past 12 months for continuing medical education, consultancy services, research grants, and/or promotional speaking from Lundbeck. The authors received editorial assistance from CHC Group (North Wales, PA), which was supported by Lundbeck LLC.