title: Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson's disease (NOH306A).
abstract: BACKGROUND
  Neurogenic orthostatic hypotension (nOH) is common in Parkinson's disease (PD), and represents a failure to generate norepinephrine responses appropriate for postural change. Droxidopa (L-threo-3,4-dihydroxyphenylserine) is an oral norepinephrine prodrug.
  
  
  OBJECTIVE
  Interim analyses of the initial patients enrolled in a multicenter, randomized, double-blind, placebo-controlled phase 3 trial of droxidopa for nOH in PD (ClinicalTrials.gov Identifier: NCT01176240).
  
  
  METHODS
  PD patients with documented nOH underwent ≤ 2 weeks of double-blind droxidopa or placebo dosage optimization followed by 8 weeks of maintenance treatment (100-600 mg t.i.d.). The primary efficacy measure was change in Orthostatic Hypotension Questionnaire (OHQ) composite score from baseline to Week 8. Key secondary variables included dizziness/lightheadedness score (OHQ item 1) and patient-reported falls.
  
  
  RESULTS
  Among 24 droxidopa and 27 placebo recipients, mean OHQ composite-score change at Week 8 was -2.2 versus -2.1 (p = 0.98); in response to this pre-planned futility analysis, the study was temporarily stopped and all data from these patients were considered exploratory. At Week 1, mean dizziness/lightheadedness score change favored droxidopa by 1.5 units (p = 0.24), with subsequent numerical differences favoring droxidopa throughout the observation period, and at Week 1, mean standing systolic blood-pressure change favored droxidopa by 12.5 mmHg (p = 0.04). Compared with placebo, the droxidopa group exhibited an approximately 50% lower rate of reported falls (p = 0.16) and fall-related injuries (post-hoc analysis).
  
  
  CONCLUSIONS
  This exploratory analysis of a small dataset failed to show benefit of droxidopa, as compared with placebo by the primary endpoint. Nonetheless, there were signals of potential benefit for nOH, including improvement in dizziness/lightheadedness and reduction in falls, meriting evaluation in further trials.
authors: University of South Florida, Tampa, FL, USA.
authors: Robert A
authors: RA
authors: Hauser
authors: Chelsea Therapeutics, Inc., Charlotte, NC, USA.
authors: L Arthur
authors: LA
authors: Hewitt
authors: Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA.
authors: Stuart
authors: S
authors: Isaacson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D015103:Droxidopa / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications*
chemical_list: D000978:Antiparkinson Agents; D015103:Droxidopa
keywords: Hypotension; Parkinson's disease; droxidopa; falls; orthostatic; treatment