Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure

Inclusion Criteria: * Subject is male or female and at least 30 years old. * Subject must meet the diagnostic criteria of symptomatic nOH, as demonstrated by a sustained reduction in BP of ≥20 mm Hg (systolic) or ≥10 mm Hg (diastolic) within 3 minutes of being tilted-up to ≥60o from a supine position as determined by a tilt-table test. * Subject must score at least a 4 on the Orthostatic Hypotension Symptom Assessment Question #1 at randomization visit. * For subjects with PD only: Subject has a diagnosis of PD according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria (1992). * For subjects with MSA only: Subject has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (2008). * For subjects with PAF only: Subject has documented impaired autonomic reflexes, including the Valsalva maneuver performed within 24 months from the date of randomization. * Subject has plasma NE levels \>100 pg/mL after being in seated position for 30 minutes. Exclusion Criteria: * Subject has a known systemic illness known to produce autonomic neuropathy, including but not limited to amyloidosis, and autoimmune neuropathies. * Subject has a known intolerance to other NRIs or SNRIs. * Subject currently uses concomitant antihypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction. * Subject has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half-lives, whichever is longer, prior to randomization or requires concomitant use until the follow-up visit. * Subject has changed dose, frequency, or type of prescribed medication for orthostatic hypotension within 7 days prior to V1. * Midodrine and droxidopa (if applicable) must be tapered off at least 7 days prior to V1. * Subject has a known or suspected alcohol or substance abuse within the past 12 months (DSM-IV-TR® definition of alcohol or substance abuse). * Subject has a clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months. * Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to randomization. * Subject has a history of untreated closed angle glaucoma, or treated closed angle glaucoma that, in the opinion of an ophthalmologist, might result in an increased risk to the subject. * Subject has any significant uncontrolled cardiac arrhythmia. * Subject has a Montreal Cognitive Assessment (MoCA) ≤23. * Subject had a myocardial infarction in the past 6 months or has current unstable angina. * Subject has known congestive heart failure (New York Heart Association \[NYHA\] Class 3 or 4). * Subject has a clinically significant abnormal laboratory findings (e.g., alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \>3.0 x upper limit of normal \[ULN\]; blood bilirubin \[total\] \>1.5 x ULN; estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2, or any abnormal laboratory value that could interfere with safety of the subject). * Subject has demonstrated a history of lifetime suicidal ideation and/or suicidal behavior, as outlined by the C-SSRS (Columbia Suicide Severity Rating Scale) (Baseline/Screening Version) subject should be assessed by the rater for risk of suicide and the subject's appropriateness for inclusion in the study.