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Treatment of Neurogenic Orthostatic Hypotension in Multiple System Atrophy

A Phase 3, Multi-center, Randomized Withdrawal and Long Term Extension Study of Ampreloxetine for the Treatment of Symptomatic Neurogenic Orthostatic Hypotension in Participants with Multiple System Atrophy

Phase 3 Interventional Theravance Biopharma · NCT05696717

This study is testing if a new medication called ampreloxetine can help people with multiple system atrophy who experience low blood pressure when standing up feel better and have lasting relief from their symptoms.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment102 (estimated)
Ages30 Years and up
SexAll
SponsorTheravance Biopharma Industry-sponsored
Locations78 sites (Scottsdale, Arizona and 77 other locations)
Trial IDNCT05696717 on ClinicalTrials.gov

What this trial studies

This Phase 3 clinical trial evaluates the efficacy and durability of ampreloxetine in treating symptomatic neurogenic orthostatic hypotension (nOH) in participants diagnosed with multiple system atrophy (MSA). The study consists of four periods: screening, open label treatment, randomized withdrawal, and a long-term treatment extension. Participants will be monitored for changes in blood pressure and symptoms related to nOH after 20 weeks of treatment. The trial aims to determine whether ampreloxetine can provide sustained relief from symptoms associated with this condition.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 30 and older with a confirmed diagnosis of possible or probable MSA and symptomatic nOH.

Not a fit: Patients with other forms of orthostatic hypotension or those who do not meet the specific diagnostic criteria for MSA may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients suffering from neurogenic orthostatic hypotension associated with multiple system atrophy.

How similar studies have performed: Other studies have explored treatments for neurogenic orthostatic hypotension, but the specific use of ampreloxetine in this context is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).
* Participant has demonstrated lifetime suicidal ideation and/or suicidal behavior, as outlined by the C-SSRS (Baseline/Screening Version). Participant should be assessed by the rater for risk of suicide and the participant's appropriateness for inclusion in the study.
* Participant has a concurrent disease or condition (e.g., COVID-19), or recent surgery, that in the opinion of the Investigator, would confound or interfere with study participation or evaluation of safety, tolerability, or absorption of the study drug.
* Participant has known hypersensitivity to ampreloxetine (ampreloxetine hydrochloride), or any excipients in the formulation.
* Major surgery (i.e., procedures involving higher risk for infection and extended recovery period, such as, joint replacement, gastric bypass, open heart surgery, organ transplant, etc.) occurring less than 4 weeks prior to enrollment.

Where this trial is running

Scottsdale, Arizona and 77 other locations

+28 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Symptomatic Neurogenic Orthostatic HypotensionMSA - Multiple System Atrophy
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.