TD-9855 Phase 2 in Neurogenic Orthostatic Hypotension (nOH)
Purpose
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.
Conditions
- 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
Eligibility
- Eligible Ages
- Over 40 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental TD-9855 Part A |
Subjects will receive placebo and escalating single doses of TD-9855 |
|
|
Experimental TD-9855 Part B |
Subjects will receive a single dose of TD-9855 or placebo. |
|
|
Experimental TD-9855 Part C |
Subjects will receive once daily doses of TD-9855 for up to 5 months as part of an optional outpatient open-label extension arm. |
|
More Details
- Status
- Completed
- Sponsor
- Theravance Biopharma
Study Contact
Detailed Description
Part A followed a daily, single-escalating-dose design, starting with placebo on Day 1, followed by a dose of 2.5 mg TD-9855 on Day 2, and proceeding to higher daily doses of TD-9855 up to a maximum dose of 20 mg based on safety, tolerability, and determination of a pressor effect. The starting dose in Part A was initially set to 1 mg (Day 2), escalating to a maximum dose of 10 mg (Day 5), but this was revised to start at 2.5 mg (Day 2) and escalate to 20 mg (Day 5) in protocol amendment 2 (Section 9.8.1). Part B followed a randomized, placebo-controlled, parallel design, evaluating an acute dose of TD-9855 that was determined to have a pressor effect and to be generally well tolerated for a given subject from Part A. Subjects who completed Part A, demonstrated a pressor effect in Part A, and remained otherwise eligible, had the option to receive open-label TD-9855 by tablet daily for up to 5 months (20 weeks) during Part C.