TD-9855 Phase 2 in Neurogenic Orthostatic Hypotension (nOH)
Condition: Neurogenic Orthostatic Hypotension; Multiple System Atrophy (MSA) With Orthostatic Hypotension; Pure Autonomic Failure; Parkinson Disease; Hypotension, Orthostatic; Orthostatic Hypotension; Pure Autonomic Failure With Orthostatic Hypotension; Parkinson Disease With Orthostatic Hypotension
MeSH terms: Parkinson Disease; Multiple System Atrophy; Shy-Drager Syndrome; Hypotension, Orthostatic; Pure Autonomic Failure; Hypotension; Atrophy
Intervention: TD-9855; Placebo
Intervention description: Administered orally.; Administered orally.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 34.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Neurogenic Orthostatic Hypotension (nOH); Multiple System Atrophy (MSA); Pure Autonomic Failure; Parkinson Disease(PD); nOH; MSA; PD; PAF; Orthostatic Hypotension; ampreloxetine; TD-9855

Summary:

      This multiple-center, 3-part, single-blind dose escalation (Part A), randomized, double-blind
      (Part B), and open-label multiple dose extension (Part C) study will be conducted in male and
      female subjects with neurogenic orthostatic hypotension to evaluate the effect of TD-9855 in
      improving symptoms of orthostatic intolerance.
    

Eligibility criteria:

        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.