Participants will be randomized to receive a single oral daily dose of ampreloxetine or placebo. Blinding will be for the investigator, participant, care provider and outcome assessor. There are three phases, a four-week screening, four weeks of randomized treatment and a two week follow up. Apart from the screening visit, the required visits can be conducted either in clinic or remotely.
The primary outcome measure is the change from baseline in Orthostatic Hyp-otension Symptom Assessment (OHSA) question #1 at week 4. Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout. The timeframe is baseline to week 4. The secondary outcome measures are: 1. Change from baseline in OHSA composite score in weeks 1 to 4 (timeframe: baseline, week 1, week 2, week 3, week 4); 2. Change from baseline in Orthostatic Hypotension Daily Activities Scale (OHDAS) composite score in weeks 1 to 4 (timeframe: baseline, week 1, week 2, week 3, week 4). OHDAS is an assessment of how low blood pressure symptoms affect daily life; 3. Using the Patient Global Impression of Change (PGI-C) scale, a subject rates their total improvement at week 4 compared to baseline; 4. Incidence of patient-reported falls at week 4.