Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure

Completed · Phase 3 · Has a placebo group

Conditions studied: Symptomatic Neurogenic Orthostatic Hypotension

In brief

A Phase 3 study to evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in subjects with primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH with up to 4 weeks of treatment.

Key facts

Study ID: NCT03750552
Run by: Theravance Biopharma
People needed: 195
Starts: 2019-01-24
Expected to finish: 2021-07-21
Last updated by the study team: 2022-09-14

Who can join

Age: 30 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Subject is male or female and at least 30 years old.
Subject must meet the diagnostic criteria of symptomatic nOH, as demonstrated by a sustained reduction in BP of ≥20 mm Hg (systolic) or ≥10 mm Hg (diastolic) within 3 minutes of being tilted-up to ≥60o from a supine position as determined by a tilt-table test.
Subject must score at least a 4 on the Orthostatic Hypotension Symptom Assessment Question #1 at randomization visit.
For subjects with PD only: Subject has a diagnosis of PD according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria (1992).
For subjects with MSA only: Subject has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (2008).
For subjects with PAF only: Subject has documented impaired autonomic reflexes, including the Valsalva maneuver performed within 24 months from the date of randomization.
Subject has plasma NE levels >100 pg/mL after being in seated position for 30 minutes.

You may not qualify if…

Subject has a known systemic illness known to produce autonomic neuropathy, including but not limited to amyloidosis, and autoimmune neuropathies.
Subject has a known intolerance to other NRIs or SNRIs.
Subject currently uses concomitant antihypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction.
Subject has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half-lives, whichever is longer, prior to randomization or requires concomitant use until the follow-up visit.
Subject has changed dose, frequency, or type of prescribed medication for orthostatic hypotension within 7 days prior to V1.
Midodrine and droxidopa (if applicable) must be tapered off at least 7 days prior to V1.
Subject has a known or suspected alcohol or substance abuse within the past 12 months (DSM-IV-TR® definition of alcohol or substance abuse).
Subject has a clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months.
Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to randomization.
Subject has a history of untreated closed angle glaucoma, or treated closed angle glaucoma that, in the opinion of an ophthalmologist, might result in an increased risk to the subject.
Subject has any significant uncontrolled cardiac arrhythmia.
Subject has a Montreal Cognitive Assessment (MoCA) ≤23.
Subject had a myocardial infarction in the past 6 months or has current unstable angina.
Subject has known congestive heart failure (New York Heart Association [NYHA] Class 3 or 4).
Subject has a clinically significant abnormal laboratory findings (e.g., alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3.0 x upper limit of normal [ULN]; blood bilirubin [total] >1.5 x ULN; estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2, or any abnormal laboratory value that could interfere with safety of the subject).
Subject has demonstrated a history of lifetime suicidal ideation and/or suicidal behavior, as outlined by the C-SSRS (Columbia Suicide Severity Rating Scale) (Baseline/Screening Version) subject should be assessed by the rater for risk of suicide and the subject's appropriateness for inclusion in the study.

Where it is running

Collaborative Neuroscience Network, LLC — Long Beach, California, United States
Stanford Neuroscience Health Center — Palo Alto, California, United States
Colorado Springs Neurological Associates, PC — Colorado Springs, Colorado, United States
University of Colorado Health — Loveland, Colorado, United States
Georgetown University Hospital, Dept. of Neurology — Washington D.C., District of Columbia, United States
Parkinson's Disease and Movement Disorders Center — Boca Raton, Florida, United States
SFM Clinical Research — Boca Raton, Florida, United States
Fixel Institute for Neurological Diseases — Gainesville, Florida, United States
Neurostudies, Inc — Port Charlotte, Florida, United States
Rush University Medical Center — Chicago, Illinois, United States
NorthShore University Health System — Glenview, Illinois, United States
University of Kansas Medical Center — Kansas City, Kansas, United States
Mayo Clinic - Rochester — Rochester, Minnesota, United States
Rutgers New Jersey Medical School — Newark, New Jersey, United States
New York University Langone Health — New York, New York, United States
University of Cincinnati Medical Center — Cincinnati, Ohio, United States
The Ohio State University Wexner Medical Center — Columbus, Ohio, United States
Oregon Health & Science University — Portland, Oregon, United States
Vanderbilt University Medical Center — Nashville, Tennessee, United States
University of Texas Southwestern Medical Center — Dallas, Texas, United States
Georgetown University Hospital — McLean, Virginia, United States
Inland Northwest Research — Spokane, Washington, United States
Concord Hospital — Concord, New South Wales, Australia
Royal Brisbane and Women's Hospital — Herston, Queensland, Australia
Banner Sun Health Research Institute — Sun City, Arizona, United States

Full record on ClinicalTrials.gov

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