Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_2

Timeline

Completed

Started Sep 2017

Shorter than P25 for phase_2

Geographic Reach

1 country

6 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

1.2 years study duration

First Submitted

Initial submission to the registry

March 7, 2016

Completed

3 days until next milestone

First Posted

Study publicly available on registry

March 10, 2016

Completed

1.5 years until next milestone

Study Start

First participant enrolled

September 9, 2017

Completed

11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 24, 2018

Completed

4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 28, 2018

Completed

3.8 years until next milestone

Results Posted

Study results publicly available

September 26, 2022

Completed

Last Updated

September 26, 2022

Status Verified

February 1, 2022

Enrollment Period

11 months

First QC Date

March 7, 2016

Results QC Date

February 24, 2022

Last Update Submit

August 30, 2022

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

Keywords

Neurogenic Orthostatic Hypotension (nOH)Multiple System Atrophy (MSA)Pure Autonomic FailureParkinson Disease(PD)nOHMSAPDPAFOrthostatic HypotensionampreloxetineTD-9855

Outcome Measures

Primary Outcomes (3)

Part A: Change From Time-matched Placebo in Seated Systolic Blood Pressure (SBP)
Placebo referred to the Day 1 visit, and the change from placebo referred to the time-matched difference from each TD-9855 dosing day (Days 2 through 5) relative to placebo dosing (Day 1).
7 hours post-dose on Day 1 (Placebo dosing) and on each of Days 2 to 5 (TD-9855 dosing)
Part B: Change From Baseline in Seated SBP
Baseline was defined as the pre-dose measurement on Day 1 of Part B.
Baseline and 7 hours post-dose on Day 1
Part C: Change From Baseline in Likert Scale Score at Week 4
The Likert Scale is question 1 of the Orthostatic Hypotension Symptom Assessment (OHSA). The question asks participants to rate the severity of their orthostatic hypotension symptoms (dizziness, lightheadedness, feeling faint, or feeling like you might black out) on an 11-point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference. A higher score indicates a worse outcome. Baseline was defined as the pre-lunch measurement on Day -1.
Baseline to Week 4

Secondary Outcomes (15)

Part A and Part B: Change From Baseline in Likert Scale Score at 6 to 8 Hours
Baseline to a single time point between 6 to 8 hours post-dose
Part A and Part B: Change From Baseline in the Composite Orthostatic Hypotension Symptom Assessment (OHSA) Score
Baseline to a single time point between 6 to 8 hours post-dose
Part A: Change From Time-matched Placebo in Standing SBP
4 and 7 hours post-dose on Day 1 (Placebo dosing) and on each of Days 2 to 5 (TD-9855 dosing)
Part B: Change From Baseline in Standing SBP
Baseline, 4 and 7 hours post-dose on Day 1
Part A: Change From Time-matched Placebo in Seated SBP
4, 7, 9, 12 hours post-dose on Day 1 (placebo) and Days 2 to 5 (TD-9855 dosing)
+10 more secondary outcomes

Study Arms (3)

TD-9855 Part A

EXPERIMENTAL

Subjects will receive placebo and escalating single doses of TD-9855

Drug: TD-9855Drug: Placebo

TD-9855 Part B

EXPERIMENTAL

Subjects will receive a single dose of TD-9855 or placebo.

Drug: TD-9855Drug: Placebo

TD-9855 Part C

EXPERIMENTAL

Subjects will receive once daily doses of TD-9855 for up to 5 months as part of an optional outpatient open-label extension arm.

Drug: TD-9855Drug: Placebo

Interventions

TD-9855DRUG

Administered orally.

TD-9855 Part ATD-9855 Part BTD-9855 Part C

PlaceboDRUG

Administered orally.

TD-9855 Part ATD-9855 Part BTD-9855 Part C

Eligibility Criteria

Age40 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

You may not qualify if:

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.

Contact the study team to confirm eligibility.