Neurogenic
orthostatic hypotension (nOH) results from failure of
norepinephrine responses to postural change to maintain standing systolic blood pressure (s-SBP).
Droxidopa is an oral
prodrug of
norepinephrine. Study nOH306 enrolled patients with
Parkinson's disease (PD) and symptomatic nOH. Subjects underwent up to 2 weeks of double-blind titration of
droxidopa or placebo, followed by 8 weeks of double-blind maintenance treatment (100-600 mg thrice-daily). For the initial 51 subjects (study nOH306A, previously reported), the primary efficacy measure,
Orthostatic Hypotension Questionnaire (OHQ) composite score, did not demonstrate significant change versus placebo at maintenance week 8. For the subsequent 171 subjects (study nOH306B, reported here), the primary efficacy measure was change versus placebo on item 1 ("
dizziness,
lightheadedness, feeling faint, or feeling like you might black out") of the
Orthostatic Hypotension Symptom Assessment (OHSA) subsection of the OHQ at maintenance week 1. At week 1, mean (standard deviation) improvement on OHSA item 1 was 2.3 (2.95) for
droxidopa versus 1.3 (3.16) for placebo (P = 0.018). In addition, mean increase in s-SBP at week 1 was 6.4 (18.85) for
droxidopa versus 0.7 (20.18) mmHg for placebo (nominal P value: 0.032). Differences in change in OHSA item 1 scores from baseline to maintenance weeks 2, 4, and 8 were not statistically significant. Adverse-event (AE) incidence was similar across groups, but 12.4% of
droxidopa and 6.1% of placebo subjects withdrew because of AEs. The most common AEs on
droxidopa (vs. placebo) were
headache (13.5% vs. 7.3%) and
dizziness (10.1% vs. 4.9%). Study nOH306B demonstrated subjective (OHSA item 1) and objective (s-SBP) evidence of short-term
droxidopa efficacy (vs. placebo) for symptomatic nOH in PD.