Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure
- Conditions
- Symptomatic Neurogenic Orthostatic Hypotension
- Interventions
- Drug: Placebo
- Registration Number
- NCT03750552
- Lead Sponsor
- Theravance Biopharma
- Brief Summary
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.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 195
- 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.
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Subject has a known systemic illness known to produce autonomic neuropathy, including but not limited to amyloidosis, and autoimmune neuropathies.
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Subject has a known intolerance to other NRIs or SNRIs.
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Subject currently uses concomitant antihypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction.
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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.
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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.
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Subject has a known or suspected alcohol or substance abuse within the past 12 months (DSM-IV-TR® definition of alcohol or substance abuse).
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Subject has a clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months.
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Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to randomization.
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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.
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Subject has any significant uncontrolled cardiac arrhythmia.
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Subject has a Montreal Cognitive Assessment (MoCA) ≤23.
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Subject had a myocardial infarction in the past 6 months or has current unstable angina.
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Subject has known congestive heart failure (New York Heart Association [NYHA] Class 3 or 4).
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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).
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks. ampreloxetine ampreloxetine Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 Score at Week 4 Baseline and Week 4 OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale where each question uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.
Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout.
A mean negative change from baseline indicates a better outcome.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score at Week 4 Baseline and Week 4 OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale in which the composite score uses 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 mean negative change from baseline indicates a better outcome.Change From Baseline in Orthostatic Hypotension Daily Activities Scale (OHDAS) Composite Score at Week 4 Baseline and Week 4 OHDAS is an assessment of how low blood pressure symptoms affect daily life. OHDAS is a 4 item assessment in which the composite score uses 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 mean negative change from baseline indicates a better outcome.Number of Participants Who Experienced an Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Week 4 Baseline and Week 4 PGI-C was assessed using a 5-point scale where participants were asked to compare their current condition to their condition at baseline from 1 to 5, with 1 indicating the condition is very much improved and 5 indicating the condition is very much worse. These scores were analyzed in 2 categories: better and no change/worse.
Number of Participants Who Experienced at Least One Fall Up to Week 4
Trial Locations
- Locations (124)
Banner Sun Health Research Institute
🇺🇸Sun City, Arizona, United States
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, 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
Scroll for more (114 remaining)Banner Sun Health Research Institute🇺🇸Sun City, Arizona, United States