Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure
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.
- Symptomatic Neurogenic Orthostatic Hypotension
- Eligible Ages
- Over 30 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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.
- 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.
- Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Parallel assignment
- Primary Purpose
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
|Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.||
|Participants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks.||
- Theravance Biopharma
Study ContactTheravance Biopharma Call Center
A Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in subjects with primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH. The study consists of 3 periods: (i) 4-week screening, (ii) 4-week randomized treatment, and (iii) 2-week follow up. The trial utilizes an operational design featuring the ability to conduct protocol required visits as either in clinic or remote visits (except Screening visit).