A Study in Subjects With Neurogenic Orthostatic Hypotension

Inclusion Criteria:

1. Male or female subjects ≥ 18 and ≤ 85 years of age, at time of informed consent.

2. Diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease orpure autonomic failure (i.e. neurogenic orthostatic hypotension).

3. At Screening, subjects must meet the diagnostic criteria of neurogenic orthostatichypotension, as demonstrated by a decrease ≥20 mm Hg in systolic or ≥10 mm Hg indiastolic BP upon standing ≤3 minutes from a supine position.

4. At Screening, subjects must have a score ≥4 on the Orthostatic Hypotension SymptomAssessment (OHSA) scale question #1.

5. Currently receiving, or known to be responsive to, direct or indirect α1-AR agonists (e.g., midodrine, droxidopa) for treatment of nOH.

6. If the Investigator determines that additional autonomic function testing isrequired to confirm the diagnosis of autonomic dysfunction, the Valsalva maneuvermay be performed to show the absence of BP overshoot during phase IV.

7. Body weight greater or equal to 50 kg and body mass index (BMI) between 18 and 35kg/m2, inclusive at Screening.

8. Stable medical conditions for 3 months prior to Screening.

9. For patients taking antiparkinsonian medication: stable dose of levodopa, dopamineagonist, amantadine, and/or monoamine oxidase B inhibitor, i.e. unchanged for 1month.

10. Subject is ambulatory with/without the use of an assistive device.

11. Willing to follow the protocol requirements and comply with protocol restrictions.

12. Capable of providing informed consent and complying with study procedures.

13. Able to speak, understand, and read English.

Exclusion Criteria:

1. Systemic illnesses known to produce autonomic neuropathy, including but not limitedto diabetes mellitus, amyloidosis, monoclonal gammopathy of unknown significance,and autoimmune neuropathies.

2. Concomitant use of vasoconstricting agents for the purpose of increasing bloodpressure (BP) such as ephedrine, dihydroergotamine, or midodrine must be stopped atleast 1 day or 5 half-lives (whichever is longer) prior to dosing on Day 1 andthroughout the duration of the study. Fludrocortisone use in the study will belimited to a stable dose of 0.1 mg once-daily (QD).

3. Supine SBP ≥ 170 mm Hg or seated SBP ≥ 140 mm Hg at Screening.

4. Subjects with clinically meaningful urinary retention who use or are likely to use α1-AR antagonists (e.g., tamsulosin [Flomax]), or other medications (e.g.,trazodone).

5. Concomitant use of anti-hypertensive medication for the treatment of essentialhypertension unrelated to autonomic dysfunction.

6. Evidence of any significant or unstable clinical disorder or laboratory finding thatrenders the subject unsuitable for receiving an investigational drug includingclinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary,gastrointestinal, endocrine (excluding managed hypo and hyperthyroidism), metabolic,renal, or other systemic disease or laboratory abnormality.

7. History of malignant disease within 5 years, including solid tumors and hematologicmalignancies (except [a] basal cell and squamous cell carcinomas of the skin thathave been completely excised and are considered cured; [b] low-grade adenocarcinomaof the prostate).

8. Any clinically significant illness or disease (apart from those typically associatedwith neurodegenerative disease) as determined by medical and surgical history,physical examination, 12-lead electrocardiogram (ECG) and clinical laboratoryassessments conducted at Screening.

9. History of suicidal ideation or an episode of clinically severe depression asdetermined by the Investigator.

10. Clinically significant abnormalities of ECG, including QTcF > 450 ms, for males andQTcF > 470 ms for females, and/or HR < 50 beats per minute, or evidence ofclinically significant bundle branch blocks, as indicated by 12-lead ECG in a supineposition at Screening.

11. A calculated eGFR of ≤60 mL/min/1.73m2 according to the Chronic KidneyDisease-Epidemiology Collaboration (CKD-EPI) equation at Screening.

12. Current use of any prohibited prescription medication during Screening or throughoutstudy, unless approved by both the Investigator and the Sponsor Medical Monitor.

13. Prior treatment with any investigational drug ≤90 days prior to dosing (Day 1), or ≤5 half-lives of the drug (whichever is longer), or current enrollment in any otherstudy treatment or disease study, except for observational studies.

14. Known or suspected alcohol or substance abuse within the past 12 months and/orpositive test for alcohol or drugs of abuse at Screening.

15. Positive screening test for human immunodeficiency virus (HIV), hepatitis C antibody (HCV Ab) or current hepatitis B infection (defined as positive for hepatitis Bsurface antigen [HbsAg] at Screening).

16. Females who are breastfeeding.

17. Any other reason for which the Investigator considers it is not in the best interestof the subject to undertake the study.