Phase 3 Efficacy and Durability of Ampreloxetine for the Treatment of Symptomatic nOH in Participants With Multiple System Atrophy

Running, not enrolling · Phase 3 · Has a placebo group

Conditions studied: Symptomatic Neurogenic Orthostatic Hypotension, MSA - Multiple System Atrophy

In brief

This is a Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment. This study includes 4 periods: Screening, open label, randomized withdrawal, and long-term treatment extension (LTE).

Key facts

Study ID

NCT05696717

Run by

Theravance Biopharma

People needed

102

Starts

2023-06-27

Expected to finish

2028-01-01

Last updated by the study team

2025-09-05

Who can join

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

You may qualify if…

• Participant is male or female and at least 30 years old.
• Participant 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).
• Participant has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) confirmed by the Enrollment Steering Committee (ESC).
• Participant must meet the diagnostic criteria of nOH, as demonstrated by a sustained reduction in BP of ≥20 mmHg (systolic) or ≥10 mmHg (diastolic) within 3 min of standing as part of orthostatic standing test or being tilted up ≥60o from a supine position as determined by a tilt-table test.
• Participant must score ≤4 on UMSARS Part IV at Visit 1 (Screening).
• Participant must score at least a 4 on the OHSA item 1 at Visit 2 (Day 1).
• Participant must be willing to not take any prohibited medications during the study.
• If participant is female, the participant must not be pregnant, breastfeeding, or planning a pregnancy during the course of the study. A woman of childbearing potential must have a documented negative pregnancy test at screening.
• During the study and for 30 days after receiving the last dose of the study drug, females of childbearing potential or males capable of fathering children must agree to use highly effective birth control measures (failure rate <1% when used consistently and correctly) or agree to abstain from sexual intercourse.
• Participant is willing and able to provide signed and dated written informed consent to -participate prior to initiation of any study related procedures.
• Participant is able to communicate well with the Investigator and clinic staff, understands the expectations of the study and is able to comply with the study procedures, requirements, and restrictions.

You may not qualify if…

• Participant has a systemic illness known to produce autonomic neuropathy, including, but not limited to, amyloidosis and autoimmune neuropathies. Participant with diabetes mellitus (DM) will be evaluated on a case-by-case basis by the medical monitor and considered ineligible unless they meet all of the following criteria:
• Well controlled type-2 DM in treatment with only oral medications and diet
• HbA1C of ≤7.5% performed during screening or up to 12 weeks before screening
• No clinically evident peripheral neuropathy (e.g., normal sensory examination on peripheral extremities)
• No known retinopathy (e.g., annual ophthalmic exam is sufficient)
• No nephropathy (e.g., absence of albuminuria and GFR >60).
• Participant has a known intolerance to other NRIs or SNRIs.
• Participant currently uses concomitant antihypertensive medication for the treatment of essential hypertension.
• Participant has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half lives, whichever is longer, prior to Visit 2 (Day 1) or requires concomitant use until the Safety follow-up Visit.
• Participant has changed dose, frequency, or type of prescribed medication for orthostatic hypotension within 7 days prior to Visit 2 (Day 1).
• Midodrine and droxidopa (if applicable) must be tapered off and stopped at least 7 days prior to Visit 2 (Day 1).
• Participant 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).
• Participant has clinically unstable coronary artery disease or had a major cardiovascular event (e.g., myocardial infarction) in the past 6 months.
• Participant has significant uncontrolled cardiac arrhythmia, history of complete heart block, or significant QTc prolongation (≥450 msec for males and ≥470 msec for females).
• Participant has a new onset of a neurological event (i.e., seizures, confusion, altered levels of consciousness, etc.) in the past 6 months.
• Participant has used any monoamine oxidase inhibitor (MAOI) within 14 days prior to Visit 2 (Day 1).
• Participant 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 participant.
• Participant has a Montreal Cognitive Assessment (MoCA) <21.
• Participant is unable or unwilling to complete all protocol specified procedures including questionnaires.
• Participant has known congestive heart failure (New York Heart Association [NYHA] Class 3 or 4).
• Participant has had any malignant disease, other than carcinoma in situ of the cervix or basal cell carcinoma, within the past 2 years prior to Screening.
• Participant has a known gastrointestinal (GI) condition, which in the Investigator's judgment, may affect the absorption of study medication (e.g., ulcerative colitis, gastric bypass).
• Participant has psychiatric, neurological, or behavioral disorders that may interfere with the cognitive ability of the participant to give informed consent, understand and comply with study procedures, or interfere with the conduct of the study.
• Participant is currently receiving any investigational drug or has received an investigational drug within 30 days of dosing. An investigational drug is defined as a drug that is not approved by a regulatory agency (e.g., Food and Drug Administration [FDA]).
• Participant has a clinically significant abnormal laboratory finding(s) (e.g., alanine aminotransferase [ALT] or aspartate aminotransferase [AST] ≥3.0 x upper limit of normal [ULN]; blood bilirubin [total] ≥3.0 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 participant).

Where it is running

• The Parkinson's and Movement Disorder Institute — Fountain Valley, California, United States
• UC San Diego Movement Disorder Center — La Jolla, California, United States
• David Geffen School of Medicine at UCLA — Los Angeles, California, United States
• Stanford Neuroscience Health Center — Palo Alto, California, United States
• Medstar Georgetown University Hospital — Washington D.C., District of Columbia, United States
• Parkinson's Disease And Movement Disorders Center of Boca Raton — Boca Raton, Florida, United States
• SFM Clinical Research, LLC — Boca Raton, Florida, United States
• Aqualane Clinical Research — Naples, Florida, United States
• Neurostudies, Inc — Port Charlotte, Florida, United States
• University of South Florida Ataxia Research Center — Tampa, Florida, United States
• Emory University — Atlanta, Georgia, United States
• Hawaii Pacific Neuroscience — Honolulu, Hawaii, United States
• Rush University Medical Center — Chicago, Illinois, United States
• Northshore University Health System — Glenview, Illinois, United States
• University of Kansas Medical Center Research Institute, Inc. — Kansas City, Kansas, United States
• Brigham and Women's Hospital (Neuromuscular Division) — Boston, Massachusetts, United States
• Massachusetts Chan Medical School — Worcester, Massachusetts, United States
• Quest Research Institute — Farmington Hills, Michigan, United States
• NYU Langone Health NYU Dysautonomia Center — New York, New York, United States
• The Neurological Institute at Columbia University Medical Center — New York, New York, United States
• University of Cincinnati Medical Center — Cincinnati, Ohio, United States
• Vanderbilt University Medical Center — Nashville, Tennessee, United States
• University of Texas Southwestern Medical Center — Dallas, Texas, United States
• Baylor College of Medicine — Houston, Texas, United States
• Movement Disorders Center of Arizona — Scottsdale, Arizona, United States

Full record on ClinicalTrials.gov

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