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

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.