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

• Status: Completed
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Theravance Biopharma; Theravance Biopharma R & D, Inc.

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.