Patients with Parkinson's disease and neurogenic orthostatic hypotension treated with droxidopa showed improvements in symptoms of dizziness and lightheadedness, and in systolic blood pressure.
Droxidopa improves the signs and symptoms of neurogenic orthostatic hypotension (NOH), including dizziness, lightheadedness, and standing systolic blood pressure, in patients with Parkinson's disease (PD), according to research presented at the 65th Annual Meeting of the American Academy of Neurology.
Neurogenic orthostatic hypotension, characterized by the failure of the autonomic system to respond to changes in posture due to inadequate norepinephrine release, is an autonomic dysfunction that is occurs in approximately 18% of patients with Parkinson's disease. Additionally, however, NOH can also occur in patients with multiple system atrophy and pure autonomic failure. Droxidopa is a synthetic catecholamine that is able to cross the blood-brain barrier, where it is directly converted to norepinephrine via decarboxylation, increasing the levels of both centrally and peripherally available norepinephrine. It is currently undergoing phase 3 trials for the treatment of symptomatic NOH in patients with primary autonomic failure.
Stuart Isaacson, MD, of the Herbert Wertheim College of Medicine at the Florida International University, and colleagues reported the results of a randomized, placebo-controlled trial involving 222 patients with a clinical diagnosis of PD plus signs and symptoms of NOH who received either placebo (n=111) or were dose-titrated to droxidopa, 100 to 600 mg, three times daily (n=111) over a 2-week double blind period followed by eight weeks of double-blind treatment. A diagnosis of NOH was defined as a composite score of 3 or higher on the Orthostatic Hypotension Questionnaire (OHQ) and a decrease in blood pressure of 20 mmHg or more systolic or 10 mmHg diastolic within three minutes of standing after sitting.
Compared with placebo, droxidopa-treated patients with Parkinson's disease exhibited improved symptoms of both dizziness and lightheadedness and systolic blood pressure at Week 1 (p=0.018 and p=0.032, respectively). Additionally, although not statistically significant, patients treated with droxidopa experienced fewer falls and fall-related injuries, including contusions, lacerations, excoriations, and fractures.
Overall, droxidopa was safe and well tolerated and did not exacerbate patients' Parkinson's disease symptoms. The most common droxidopa-associated adverse events included headache (13.2% vs 7.4% for droxidopa and placebo, respectively), dizziness (9.6% vs. 4.6%), nausea (8.8% vs. 4.6%), fatigue (7.0% vs. 5.6%), and hypertension (7.0% vs. 0.9%). Importantly, many of the study participants were taking a dopa-decarboxylase inhibitor, the enzyme that converts droxidopa to norepinephrine. Neither the symptomatic effects of droxidopa nor its effect on standing systolic blood pressure appeared to be affected by dopa-decarboxylase inhibitor use.
“There remains a significant unmet need for new treatment options in NOH, an orphan disease which remains challenging to study. The empiric, data-driven approach taken in studying droxidopa to date reveals a remarkably consistent, clinically meaningful effect across studies, as well as good tolerability. This study, in particular, highlights droxidopa's significant improvements on the symptoms of dizziness/lightheadedness and standing systolic blood pressure at one week, as well as important effects on falls and fall related injuries. These data suggest that droxidopa is an important new therapy for patients living with Parkinson's disease and symptomatic NOH," the authors concluded.
This study was supported by Chelsea Therapeutics.