Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension

Inclusion Criteria:

• 18 years or older and able to stand (with or without limited assistance)
• Clinical diagnosis of symptomatic orthostatic hypotension associated with PrimaryAutonomic Failure (PD, MSA or PAF) or NDAN or DBH Deficiency
• Score of at least 4 or greater on Orthostatic Hypotension Symptom Assessment (OHSA)Item #1 (measured at Screening [Visit 1] and the first Titration Visit [Visit 2a]prior to dosing)
• A documented drop of at least 20 millimeters of mercury (mmHg) in SBP, within 3minutes of standing. This can either be documented in the patient history or assessedduring Screening prior to the first Titration Visit (Visit 2a)
• Provide written informed consent to participate in the study and understand that theymay withdraw their consent at any time without prejudice to their future medical care Additional inclusion criteria for patients taking prescribed droxidopa prior to studyentry: Patients who are taking prescribed droxidopa therapy are eligible to participate in thestudy if they meet the other inclusion criteria and also have been on a stable dose ofprescribed droxidopa for at least 2 weeks prior to the Screening Visit (Visit 1). Inaddition, they must meet either of the following at the Screening Visit (Visit 1):
• The patient's Visit 1 OHSA Item #1 score is ≥ 7 AND the prescribed dose is ≤ 300 mgthree times daily (TID); OR
• The patient's Visit 1 OHSA Item #1 score is ≤6 AND worsens by ≥ 2 units when retestedafter washing out of droxidopa for at least 3 days

Exclusion Criteria:

• In the investigator's opinion, the patient is not able to understand or cooperate withstudy procedures
• Known or suspected alcohol or substance use disorder within the past 12 months (DSM-5criteria)
• Women who are pregnant or breastfeeding
• Women of childbearing potential (WOCP) who are not using at least one method ofcontraception with their partner
• Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHgdiastolic. Sustained is defined as the average of 3 observations each at least 10minutes apart with the patient having been supine and at rest for at least 5 minutesprior to each measurement.
• Untreated closed angle glaucoma
• Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine hypertension are allowed inthis study)
• Any significant uncontrolled cardiac arrhythmia
• History of myocardial infarction or stroke, within the past 2 years
• Current unstable angina
• Congestive heart failure (NYHA Class 3 or 4)
• Diabetic autonomic neuropathy
• History of cancer within the past 2 years other than a successfully treated,non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer insitu
• Any major surgical procedure within the past 30 days
• Currently receiving any investigational drug or have received an investigational drugwithin the past 28 days Additional protocol defined exclusion criteria do apply