TD-9855 Phase 2 in Neurogenic Orthostatic Hypotension (nOH)

Inclusion Criteria:

- Diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease,
multiple system atrophy, or pure autonomic failure, (i.e. neurogenic orthostatic
hypotension).

- At screening, subject must meet the diagnostic criteria of neurogenic orthostatic
hypotension, as demonstrated by a ≥ 30 mm Hg drop in systolic blood pressure (SBP)
within 5 minutes of standing.

- Impaired autonomic reflexes, as determined by absence of BP overshoot during phase IV
of the Valsalva maneuver, in subjects where Valsalva is performed, as appropriate.

- For the optional open-label extension study subjects must have demonstrated a pressor
effect and completed dosing in Part A.

Exclusion Criteria:

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

- Concomitant use of vasoconstricting agents for the purpose of increasing BP such as
ephedrine, dihydroergotamine, or midodrine must be stopped at least 2 days or five
half lives (whichever is longer) prior to dosing on Day 1 of Part A and C, and
throughout the duration of Part C. Subjects previously enrolled in Part A under
previous versions of the protocol will continue taking fludrocortisone during the
washout period and in Part C at the dose and regimen used in Part A. For new subjects
enrolling in Part A under Amendment 3, fludrocortisone use in both Parts of the study
and during the washout period will be limited to 0.1 mg QD.

- Concomitant use of anti-hypertensive medication for the treatment of essential
hypertension unrelated to autonomic dysfunction.

- Known or suspected alcohol or substance abuse within the past 12 months.