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

Last updated: December 20, 2024
Sponsor: Theravance Biopharma
Overall Status: Active - Recruiting

Phase

3

Condition

Dizzy/fainting Spells

Circulation Disorders

Vascular Diseases

Treatment

Ampreloxetine

Placebo

Clinical Study ID

NCT05696717
2022-003903-14
  • Ages > 30
  • All Genders

Study Summary

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).

Eligibility Criteria

Inclusion

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 sustainedreduction in BP of ≥20 mmHg (systolic) or ≥10 mmHg (diastolic) within 3 min ofstanding as part of orthostatic standing test or being tilted up ≥60o from a supineposition 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, orplanning a pregnancy during the course of the study. A woman of childbearingpotential 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 agreeto use highly effective birth control measures (failure rate <1% when usedconsistently and correctly) or agree to abstain from sexual intercourse.

  • Participant is willing and able to provide signed and dated written informed consentto -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

Exclusion Criteria:

  • Participant has a systemic illness known to produce autonomic neuropathy, including,but not limited to, amyloidosis and autoimmune neuropathies. Participant withdiabetes mellitus (DM) will be evaluated on a case-by-case basis by the medicalmonitor 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 examinationon 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 treatmentof essential hypertension.

  • Participant has used strong CYP1A2 inhibitors or inducers within 7 days or 5 halflives, whichever is longer, prior to Visit 2 (Day 1) or requires concomitant useuntil the Safety follow-up Visit.

  • Participant has changed dose, frequency, or type of prescribed medication fororthostatic hypotension within 7 days prior to Visit 2 (Day 1).

  • Midodrine and droxidopa (if applicable) must be tapered off and stopped at least 7days prior to Visit 2 (Day 1).

  • Participant has known or suspected alcohol or substance abuse within the past 12months (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, TextRevision [DSM IV TR®] definition of alcohol or substance abuse).

  • Participant has clinically unstable coronary artery disease or had a majorcardiovascular event (e.g., myocardial infarction) in the past 6 months.

  • Participant has significant uncontrolled cardiac arrhythmia, history of completeheart block, or significant QTc prolongation (≥450 msec for males and ≥470 msec forfemales).

  • 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 toVisit 2 (Day 1).

  • Participant has a history of untreated closed angle glaucoma, or treated closedangle glaucoma that, in the opinion of an ophthalmologist, might result in anincreased risk to the participant.

  • Participant has a Montreal Cognitive Assessment (MoCA) <21.

  • Participant is unable or unwilling to complete all protocol specified proceduresincluding 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 thecervix or basal cell carcinoma, within the past 2 years prior to Screening.

  • Participant has a known gastrointestinal (GI) condition, which in the Investigator'sjudgment, may affect the absorption of study medication (e.g., ulcerative colitis,gastric bypass).

  • Participant has psychiatric, neurological, or behavioral disorders that mayinterfere with the cognitive ability of the participant to give informed consent,understand and comply with study procedures, or interfere with the conduct of thestudy.

  • Participant is currently receiving any investigational drug or has received aninvestigational drug within 30 days of dosing. An investigational drug is defined asa drug that is not approved by a regulatory agency (e.g., Food and DrugAdministration [FDA]).

  • Participant has a clinically significant abnormal laboratory finding(s) (e.g.,alanine aminotransferase [ALT] or aspartate aminotransferase [AST] ≥3.0 x upperlimit of normal [ULN]; blood bilirubin [total] ≥3.0 x ULN; estimated glomerularfiltration rate (eGFR) <30 mL/min/1.73 m2, or any abnormal laboratory value thatcould interfere with safety of the participant).

  • Participant has demonstrated lifetime suicidal ideation and/or suicidal behavior, asoutlined by the C-SSRS (Baseline/Screening Version). Participant should be assessedby the rater for risk of suicide and the participant's appropriateness for inclusionin the study.

  • Participant has a concurrent disease or condition (e.g., COVID-19), or recentsurgery, that in the opinion of the Investigator, would confound or interfere withstudy participation or evaluation of safety, tolerability, or absorption of thestudy drug.

  • Participant has known hypersensitivity to ampreloxetine (ampreloxetinehydrochloride), or any excipients in the formulation.

  • Major surgery (i.e., procedures involving higher risk for infection and extendedrecovery period, such as, joint replacement, gastric bypass, open heart surgery,organ transplant, etc.) occurring less than 4 weeks prior to enrollment.

Study Design

Total Participants: 102
Treatment Group(s): 2
Primary Treatment: Ampreloxetine
Phase: 3
Study Start date:
June 27, 2023
Estimated Completion Date:
January 31, 2027

Connect with a study center

  • Hospital Británico de Buenos Aires

    Caba, C1280AEB
    Argentina

    Active - Recruiting

  • Hospital General de Agudos Jose Maria Ramos Mejía

    Caba, C1221ADC
    Argentina

    Active - Recruiting

  • INEBA Instituto Neurociencias Buenos Aires

    Caba, C1192AAW
    Argentina

    Active - Recruiting

  • Instituto Fleni

    Caba, C1428AQK
    Argentina

    Active - Recruiting

  • Médico/Hospital de la Policía Federal Churruca Visca

    Caba, C1437JCP
    Argentina

    Active - Recruiting

  • Fundación Scherbovsky

    Mendoza, M5500
    Argentina

    Active - Recruiting

  • Theravance Biopharma Investigative Site

    Clayton, Victoria 3168
    Australia

    Active - Recruiting

  • Theravance Biopharma Investigative Site

    Melbourne, Victoria 3168
    Australia

    Active - Recruiting

  • Theravance Biopharma Investigative Site

    Parkville, Victoria 3050
    Australia

    Active - Recruiting

  • Medical University of Innsbruck

    Innsbruck, A-6020
    Austria

    Active - Recruiting

  • Universitatsklinikum Tulln

    Tulln,
    Austria

    Active - Recruiting

  • UZA - Antwerp University Hospital - Department of Neurology

    Edegem,
    Belgium

    Site Not Available

  • Instituto de Neurologia de Curitiba S\C LTDA

    Curitiba, PR 81210-310
    Brazil

    Active - Recruiting

  • Hospital de Clínicas - Universidade Federal de Minas Gerais (HC - UFMG)

    Belo Horizonte, 30130-100
    Brazil

    Active - Recruiting

  • Centro de Pesquisa Clínica (CPC) do Hospital das Clínicas de Porto Alegre (HCPA)

    Porto Alegre, 90035-903
    Brazil

    Active - Recruiting

  • Hospital São Lucas - PUCRS

    Porto Alegre, 90610-000
    Brazil

    Active - Recruiting

  • Hospital da Bahia

    Salvador, 41810-011
    Brazil

    Active - Recruiting

  • University of Calgary - Health Sciences Centre

    Calgary, Alberta T2N 4Z6
    Canada

    Active - Recruiting

  • Corporación de Investigación de Neurología de Santiago (Usa instalaciones de Clínica Dávila)

    Recoleta, Región Metropolinata 8431657
    Chile

    Site Not Available

  • Centro de Estudios de Trastornos del Movimiento Humano (CETRAM)

    Santiago, Región Metropolinata 9120500
    Chile

    Site Not Available

  • Bispebjerg Hospital

    Copenhagen, 2400-NV
    Denmark

    Active - Recruiting

  • Astra Cinic (Clinic4U)

    Tallinn, 11315
    Estonia

    Site Not Available

  • Astra Clinic (Clinic4U)

    Tallinn, 11315
    Estonia

    Active - Recruiting

  • Tartu University Hospital

    Tartu, 30029
    Estonia

    Active - Recruiting

  • Theravance Biopharma Investigative Site

    Nimes, Occitanie Cedex 9
    France

    Active - Recruiting

  • Centre Hospitalier Universitaire de Bordeaux Health

    Bordeaux, 33076
    France

    Active - Recruiting

  • Centre d'Investigation Clinique Hôpital Pierre Paul Rique

    Toulouse, 31059 Cedex
    France

    Active - Recruiting

  • Praxis Dr. Oehlwein, Outpatient Clinic

    Gera, Thueringen 07551
    Germany

    Active - Recruiting

  • Charite Universitaetsmedizin Berlin

    Berlin, 12203
    Germany

    Active - Recruiting

  • Charité - Universitätsmedizin Berlin- Campus Mitte

    Berlin, 10117
    Germany

    Active - Recruiting

  • Semmelweis Egyetem

    Budapest, 1085
    Hungary

    Active - Recruiting

  • Department of Neurology, University of Pécs, Hungary

    Pécs, 7623
    Hungary

    Site Not Available

  • Theravance Biopharma Investigative Site

    Tel Aviv, 64239
    Israel

    Active - Recruiting

  • IRCCS Istituto de Scienze Neurologiche di Bologna (ISNB)

    Bologna, 40139
    Italy

    Active - Recruiting

  • AOU Policlinico-San Marco, Clinica Neurologica

    Catania, 95123
    Italy

    Site Not Available

  • Fondazione Università Gabriele D'Annunzio Chieti-Pescara

    Chieti, 66100
    Italy

    Site Not Available

  • Fondazione IRCCS CA' Granda Ospedale

    Milan, 20122
    Italy

    Site Not Available

  • Parkinson's Centre of Ospedale CTO

    Milano, 20126
    Italy

    Active - Recruiting

  • Azienda Ospedaliera Universitaria Policlinico Tor Vergata

    Rome, 00133
    Italy

    Active - Recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Rome, 00168
    Italy

    Active - Recruiting

  • AOU San Giovanni di Dio e Ruggi d'Aragona, Salerno

    Salerno, 84131
    Italy

    Active - Recruiting

  • Azienda Ospedaliera Santa Maria di Terni

    Terni, I-05100
    Italy

    Active - Recruiting

  • Santa Chiara Hospital

    Trento, 38122
    Italy

    Active - Recruiting

  • Pia Fond. Cardinale Giovanni Panico Azienda Ospedaliera

    Tricase, 73039
    Italy

    Active - Recruiting

  • Theravance Biopharma Investigative Site

    Grafton, Auckland 1023
    New Zealand

    Active - Recruiting

  • Theravance Biopharma Investigative Site

    Christchurch, 8011
    New Zealand

    Active - Recruiting

  • Neurocentrum-Miwomed

    Gdańsk, 80-207
    Poland

    Active - Recruiting

  • Neuro-Care Sp. z o.o. Sp. Komandytowa

    Katowice, 40-749
    Poland

    Active - Recruiting

  • Krakowska Akademia Neurologii Sp.zo.o.

    Kraków, 31-505
    Poland

    Active - Recruiting

  • Instytut Zdrowia dr Boczarska-Jedynak Sp. z o.o., Sp.k.

    Oświęcim, 32-600
    Poland

    Active - Recruiting

  • Neuro-Care Sp. z o.o. Sp. Komandytowa

    Siemianowice Śląskie, 41-100
    Poland

    Site Not Available

  • CNS-Campus Neurologico Senior

    Torres Vedras, 2560-280
    Portugal

    Active - Recruiting

  • Fundació Assistencial Mutua de Terrassa

    Terrassa, Barcelona 08222
    Spain

    Active - Recruiting

  • Hospital Germans Trias i Pujol, Department of Neurology

    Barakaldo, Bizkaia 48903
    Spain

    Active - Recruiting

  • Instituto Investigación Sanitaria Biocruces

    Barakaldo, Bizkaia 48903
    Spain

    Active - Recruiting

  • Hospital Universitario Infante Sofia Paseo Europa

    Madrid, 28702
    Spain

    Active - Recruiting

  • Hospital Universitario de La Princesa

    Madrid, 28006
    Spain

    Active - Recruiting

  • Theravance Biopharma Investigative Site

    Taipei City, 106
    Taiwan

    Active - Recruiting

  • University Hospitals Birmingham NHS Foundation Trust

    Birmingham, B15 2GW
    United Kingdom

    Active - Recruiting

  • Autonomic Unit, National Hospital for Neurology & Neurosurgery

    London, WC1N 3BG
    United Kingdom

    Active - Recruiting

  • Barts Health

    London, EC1M 6BQ
    United Kingdom

    Active - Recruiting

  • Salford Royal Hospital

    Salford, M6 8HD
    United Kingdom

    Active - Recruiting

  • Movement Disorders Center of Arizona

    Scottsdale, Arizona 85258
    United States

    Active - Recruiting

  • The Parkinson's and Movement Disorder Institute

    Fountain Valley, California 92708
    United States

    Active - Recruiting

  • UC San Diego Movement Disorder Center

    La Jolla, California 92037
    United States

    Active - Recruiting

  • Science 37

    Los Angeles, California 90230
    United States

    Site Not Available

  • Stanford Neuroscience Health Center

    Palo Alto, California 94304
    United States

    Active - Recruiting

  • Medstar Georgetown University Hospital

    Washington, District of Columbia 20007
    United States

    Site Not Available

  • Medstar Georgetown University Hospital

    Washington DC, District of Columbia 20007
    United States

    Active - Recruiting

  • Parkinson's Disease And Movement Disorders Center of Boca Raton

    Boca Raton, Florida 33486
    United States

    Active - Recruiting

  • SFM Clinical Research, LLC

    Boca Raton, Florida 33487
    United States

    Active - Recruiting

  • Aqualane Clinical Research

    Naples, Florida 34105
    United States

    Active - Recruiting

  • Neurostudies

    Port Charlotte, Florida 33952
    United States

    Active - Recruiting

  • Neurostudies, Inc

    Port Charlotte, Florida 33952
    United States

    Site Not Available

  • Neurostudies, Inc.

    Port Charlotte, Florida 33952
    United States

    Site Not Available

  • University of South Florida Ataxia Research Center

    Tampa, Florida 33612
    United States

    Active - Recruiting

  • Vero Beach Neurology and Research Institute

    Vero Beach, Florida 32960
    United States

    Site Not Available

  • Rare Disease Research NC, LLC

    Atlanta, Georgia 30329
    United States

    Site Not Available

  • Theravance Biopharma Investigative Site

    Atlanta, Georgia 30329
    United States

    Active - Recruiting

  • Hawaii Pacific Neuroscience

    Honolulu, Hawaii 96817
    United States

    Site Not Available

  • Theravance Biopharma Investigational Site

    Boise, Idaho 83642
    United States

    Site Not Available

  • Morgan Family Medical

    Meridian, Idaho 83642
    United States

    Site Not Available

  • Rush University Medical Center

    Chicago, Illinois 60612
    United States

    Active - Recruiting

  • Northshore University Health System

    Glenview, Illinois 60026-1339
    United States

    Active - Recruiting

  • University of Kansas Medical Center Research Institute, Inc.

    Kansas City, Kansas 66160
    United States

    Active - Recruiting

  • TBPH Investigative Site

    Boston, Massachusetts 02114
    United States

    Active - Recruiting

  • Massachusetts Chan Medical School

    Worcester, Massachusetts 01655
    United States

    Active - Recruiting

  • Quest Research Institute

    Farmington Hills, Michigan 48334
    United States

    Site Not Available

  • International Medical Clinic PLLC

    Pontiac, Michigan 48302
    United States

    Site Not Available

  • NYU Langone Health NYU Dysautonomia Center

    New York, New York 10016
    United States

    Active - Recruiting

  • The Neurological Institute at Columbia University Medical Center

    New York, New York 10032
    United States

    Active - Recruiting

  • Rare Disease Research NC, LLC

    Hillsborough, North Carolina 27278
    United States

    Site Not Available

  • University of Cincinnati Medical Center

    Cincinnati, Ohio 45219
    United States

    Active - Recruiting

  • Hightower Clinical Research

    Ardmore, Oklahoma 73401
    United States

    Site Not Available

  • Neurology Care

    Ardmore, Oklahoma 73401
    United States

    Active - Recruiting

  • Vanderbilt University Medical Center

    Nashville, Tennessee 37232
    United States

    Active - Recruiting

  • University of Texas Southwestern Medical Center

    Dallas, Texas 75390
    United States

    Active - Recruiting

  • Theravance Biopharma Investigative Site

    Houston, Texas 77030
    United States

    Active - Recruiting

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