ACTIVE_NOT_RECRUITING

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

Conditions

Symptomatic Neurogenic Orthostatic Hypotension MSA - Multiple System Atrophy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

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

Quick Facts

Study Start:2023-06-27

Study Completion:2028-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05696717

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 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.

Inclusion Criteria

Exclusion 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 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.

Contacts and Locations

Study Locations (Sites)

Movement Disorders Center of Arizona

Scottsdale, Arizona, 85258

United States

The Parkinson's and Movement Disorder Institute

Fountain Valley, California, 92708

United States

UC San Diego Movement Disorder Center

La Jolla, California, 92037

United States

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095

United States

Stanford Neuroscience Health Center

Palo Alto, California, 94304

United States

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007

United States

Parkinson's Disease And Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486

United States

SFM Clinical Research, LLC

Boca Raton, Florida, 33487

United States

Aqualane Clinical Research

Naples, Florida, 34105

United States

Neurostudies, Inc

Port Charlotte, Florida, 33952

United States

University of South Florida Ataxia Research Center

Tampa, Florida, 33612

United States

Emory University

Atlanta, Georgia, 30329

United States

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817

United States

Rush University Medical Center

Chicago, Illinois, 60612

United States

Northshore University Health System

Glenview, Illinois, 60026-1339

United States

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66160

United States

Brigham and Women's Hospital (Neuromuscular Division)

Boston, Massachusetts, 02115

United States

Massachusetts Chan Medical School

Worcester, Massachusetts, 01655

United States

Quest Research Institute

Farmington Hills, Michigan, 48334

United States

NYU Langone Health NYU Dysautonomia Center

New York, New York, 10016

United States

The Neurological Institute at Columbia University Medical Center

New York, New York, 10032

United States

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219

United States

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

United States

University of Texas Southwestern Medical Center

Dallas, Texas, 75390

United States

Baylor College of Medicine

Houston, Texas, 77030

United States

Movement Disorders and Autonomic Disorders Clinic; University of Utah

Salt Lake City, Utah, 84108

United States

Collaborators and Investigators

Sponsor: Theravance Biopharma

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-27

Study Completion Date2028-01

Study Record Updates

Study Start Date2023-06-27

Study Completion Date2028-01

Terms related to this study

Additional Relevant MeSH Terms

Symptomatic Neurogenic Orthostatic Hypotension
MSA - Multiple System Atrophy