Status:
TERMINATED
Phase 3 Clinical Effect Durability of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure
Lead Sponsor:
Theravance Biopharma
Conditions:
Symptomatic Neurogenic Orthostatic Hypotension
MSA
Eligibility:
All Genders
30+ years
Phase:
PHASE3
Brief Summary
A Phase 3, 22-week, Multi-center, Randomized Withdrawal Study of ampreloxetine in Treating Symptomatic Neurogenic Orthostatic Hypotension in Subjects with Primary Autonomic Failure
Detailed Description
Phase 3, multi-center, randomized withdrawal study to evaluate the sustained benefit in efficacy and safety of ampreloxetine in subjects with primary autonomic failures (MSA, PD, or PAF) and symptomat...
Eligibility Criteria
Inclusion
- Inclusion Criteria (For 0169 Completers Group):
- Subject has completed 4 weeks of double blind treatment in Study 0169 (V6) and, in the opinion of the Investigator, could benefit from continued treatment with ampreloxetine. Only subjects with OHSA#1 score of ≤7 will be eligible for randomization for the double-blind treatment period.
- Subject has a minimum of 80% study medication compliance in Study 0169.
- Inclusion Criteria (For De Novo Group):
- 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 min of being tilted-up ≥60o from a supine position as determined by a tilt-table test.
- Subject must score at least a 4 on the OHSA#1 at V1.
- 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 Norepinephrine (NE) levels ≥ 100 pg/mL after being in seated position for 30 minutes.
- Exclusion Criteria (For 0169 Completers Group):
- Subject has a medical, laboratory, or surgical issue(s) deemed by the investigator to be clinically significant.
- Subject has an uncooperative attitude or reasonable likelihood of non-compliance with the protocol.
- Subject has a concurrent disease or condition that, in the opinion of the investigator, would confound or interfere with study participation or evaluation of safety, tolerability, or pharmacokinetics of the study drug.
- Exclusion Criteria (For De Novo Group):
- 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 serotonin norepinephrine reuptake inhibitors (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 V1 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 known or suspected alcohol or substance abuse within the past 12 months (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision \[DSM-IV-TR®\] definition of alcohol or substance abuse).
- Subject has a clinically unstable coronary artery disease, or has had a major cardiovascular or neurological event in the past 6 months.
- Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to V1.
- 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 is unable or unwilling to complete all protocol specified procedures including questionnaires.
- 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 finding (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/1.73 m2, 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 Columbia Suicide Severity Rating Scale (C-SSRS)(Baseline/Screening Version). Subject should be assessed by the rater for risk of suicide and the subject's appropriateness for inclusion in the study.
Exclusion
Key Trial Info
Start Date :
February 22 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 10 2021
Estimated Enrollment :
203 Patients enrolled
Trial Details
Trial ID
NCT03829657
Start Date
February 22 2019
End Date
November 10 2021
Last Update
January 20 2023
Active Locations (82)
Enter a location and click search to find clinical trials sorted by distance.
1
Banner Sun Health Research Institute
Sun City, Arizona, United States, 85351
2
UC San Diego Movement Disorder Center
La Jolla, California, United States, 92307
3
Stanford Neuroscience Health Center
Palo Alto, California, United States, 94304
4
Colorado Springs Neurological Associates, PC
Colorado Springs, Colorado, United States, 80907