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Symptomatic Neurogenic Orthostatic HypotensionPhase 3REDWOODNCT03829657

Phase 3 Clinical Effect Durability of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure

A Phase 3 study testing ampreloxetine in people with Symptomatic Neurogenic Orthostatic Hypotension and MSA, run by Theravance Biopharma at 82 sites in 19 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 30 years and older
What is being tested?
ampreloxetine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
203 participants
Where
82 sitesin 19 countries
Study dates
22 Feb 2019to 10 Nov 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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).
Show all 9Show fewer
  • 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.

Who cannot join

  • 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.
  • 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.
Show all 20Show fewer
  • 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.

Trial locations and contacts

82 sites in 19 countries.

82 sites in 19 countries

United States20 sites

  • Parkinson's Disease and Movement Disorders Center

    Boca Raton, Florida, 33486

  • SFM Clinical Research, LLC

    Boca Raton, Florida, 33487

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Cincinnati Medical Center (UCGNI)

    Cincinnati, Ohio, 45219

  • Colorado Springs Neurological Associates, PC

    Colorado Springs, Colorado, 80907

  • Ohio State University - Wexner Medical Center

    Columbus, Ohio, 43210

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • NorthShore University Health System

    Glenview, Illinois, 60026

  • University of Kansas Medical Center Research Institute, Inc.

    Kansas City, Kansas, 66160

  • UC San Diego Movement Disorder Center

    La Jolla, California, 92307

  • Georgetown University Hospital

    McLean, Virginia, 22101

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • New York University Langone Health

    New York, New York, 10016

  • Stanford Neuroscience Health Center

    Palo Alto, California, 94304

  • Neurostudies, Inc

    Port Charlotte, Florida, 33952

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Inland Northwest Research

    Spokane, Washington, 99202

  • Banner Sun Health Research Institute

    Sun City, Arizona, 85351

  • Wake Forest University Baptist Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Italy9 sites

  • Universita di Bologna-Clinica Neurologica - Dipt di Scienze Neurologiche Ospedale Bellaria

    Bologna, 40139

  • Azienda Ospedaliera Universitaria Policlinico - Vittorio Emanuele (Presidio Gaspare Rodolico)

    Catania, 95125

  • Universita degli studi Gabriele D' Annunzio Chieti

    Chieti, 66100

  • Fondazione IRCCS CA Granda Ospedale Maggiore Policlinico

    Milan, 20122

  • Azienda Ospedaliero-Universitaria Pisana- Ospedale S. Chiara, U.O. di Neurologia - Neurofisiopatologia

    Pisa, 56126

  • Fondazione PTV - Policlinico Tor Vergata I U.0.C. Neurologia

    Roma, 00133

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS / Istituto di Neurologia - Ambulatorio Disturbi del Movimento

    Roma, 00168

  • AOU San Giovanni di Dio e Ruggi d'Aragona

    Salerno, 84131

  • A.O. Santa Maria

    Terni, 05100

Other trials in Italy

United Kingdom7 sites

  • Royal Devon and Exeter Hospital NHS Trust

    Exeter, Devon, EX2 5DW

  • Clinical Research Centre, William Harvey Heart Centre

    London, EC1M 6BQ

  • King's College Hospital

    London, SE5 9RS

  • Re:Cognition Health Ltd

    London, W1G 9JF

  • The National Hospital for Neurology & Neurosurgery

    London, WC1N 3BG

  • Cognition Health Unit 2

    Plymouth, Devon, PL6 8BT

  • Salford Royal NHS Foundation Trust

    Salford, Greater Manchester, M6 8HD

Other trials in United Kingdom

Poland6 sites

  • Specjalistyczna Praktyka Lekarska, Prof. Grzegorz Opala

    Katowice, 40-588

  • Krakowska Akademia Neurologii Sp. Zo.o. Centrum Neurologii Klinicznej

    Krakow, 31-505

  • Instytut Zdrowia dr Boczarska-Jedynak

    Oświęcim, 32-600

  • NEURO-CARE Sp. z o.o. Sp. Komandytowa

    Siemianowice Śląskie, 41-100

  • ETG Warszawa

    Warsaw, 02-777

  • Specjalistyczne Gabinety sp. z o.o.

    Warsaw, 30-539

Other trials in Poland

Russia6 sites

  • FSBI Federal Sibirian Scientific and Clinical Center of Federal Medico-Biological Agency

    Krasnoyarsk, 660037

  • State Budgetary Institution of Healthcare of Novosibirsk region City Clinical Hospital #34

    Novosibirsk, 630054

  • City Neurological Center Sibneiromed, LLC

    Novosibirsk, 630091

  • Saint Petersburg State Budgetary Institution of Healthcare City Hospital #40 of Kurortnyi Region

    Saint Petersburg, Sestroretsk, 197706

  • FSBI National Medical Research Centre of psychiatry and neurology named after V.M. Bekhterev of the MOH of the Russian Federation

    Saint Petersburg, 192019

  • FSBI of Science Institute of Human Brain named after N .P. Bekhtereva of Russian Academy of Sciences

    Saint Petersburg, 197376

Other trials in Russia

Spain5 sites

  • Hospital del Mar

    Barcelona, 08003

  • Hospital de Cruces

    Bilbao, Vizcaya, 48903

  • Hospital Universitario de La Princesa

    Madrid, 28006

  • Complejo Hospitalario de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario Mutua de Terrasa

    Terrassa, Barcelona, 08221

Other trials in Spain

Australia4 sites

  • Clinical Trials Centre, Level 3 Monash Health Translational Precinct Building Monash Medical Centre

    Clayton, Victoria, 3168

  • Concord Hospital, Neurosciences Department

    Concord, New South Wales, 02139

  • Perron Institute for Neurological and Translational Science

    Nedlands, Western Australia, 6009

  • The Royal Melbourne Hospital Neurology Department

    Parkville, Victoria, 3050

Other trials in Australia

Canada3 sites

  • University of Calgary Teaching Research and Wellness Building

    Calgary, Alberta, T2N 4Z6

  • Montreal Neurological Institute & Hospital

    Montreal, Quebec, H3A 2B4

  • Toronto Western Hospital

    Toronto, Ontario, M5T 2S8

Other trials in Canada

Estonia3 sites

  • East Tallinn Central Hospital

    Tallinn, 10138

  • Astra Team Clinic

    Tallinn, 11315

  • Tartu University Hospital

    Tartu, 50406

Other trials in Estonia

Germany3 sites

  • Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin

    Berlin, 12203

  • Charite - Campus Virchow-Klinikum, Klinik fur Neurologie

    Berlin, 13353

  • Praxis Dr. med. Christian Oehlwein

    Gera, 7551

Other trials in Germany

Israel3 sites

  • Rabin Medical Center, Beilinson Campus

    Petah Tikva, 4941492

  • Kaplan Medical Center

    Rehovot, 76100

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 6423906

Other trials in Israel

Ukraine3 sites

  • Communal Noncommercial Enterprise City Policlinic #9 of Kharkiv City Council

    Kharkiv, 61172

  • Communal Noncommercial Enterprise of Lviv Regional Council Lviv Regional Clinical Hospital

    Lviv, 79010

  • Communal Institution Acad. O.I. Yuschenko VRPsH Vinnytsia M.I. Pyrogov NMU Ch of ND with the Course of Neurosurgery

    Vinnytsia, 21005

Other trials in Ukraine

Austria2 sites

  • Medizinische Universitat Innsbruck, Abteilung fur Neurologie

    Innsbruck, 6020

  • Universitatsklinikum Tulln Abteilung fur Neurologie

    Tulln, 3430

Other trials in Austria

Denmark2 sites

  • Bispebjerg Hospital

    Copenhagen, 2400

  • Odense Universitetshospital

    Odense, 5000

Other trials in Denmark

Portugal2 sites

  • Hospital da Senhora da Oliveira Guimarães

    Guimarães, 4835-044

  • CNS-Campus Neurologico Senior

    Torres Vedras, 2560-280

Other trials in Portugal

Bulgaria1 site

  • MHATNP Sv. Naum EAD Clinic of Neurological Diseases for Locomotor Disorders

    Sofia, 1113

Other trials in Bulgaria

France1 site

  • CHU de Nîmes - Hôpital Caremeau

    Nîmes, 30029

Other trials in France

Hungary1 site

  • Semmelweis Egyetem, Neurologiai Klinika

    Budapest, 1083

Other trials in Hungary

New Zealand1 site

  • New Zealand Brain Research Institute

    Christchurch, 8011

Other trials in New Zealand

About this study

Official title: A Phase 3, 22-week, Multi-center, Randomized Withdrawal Study of TD-9855 in Treating Symptomatic Neurogenic Orthostatic Hypotension in Subjects With Primary Autonomic Failure

A Phase 3, 22-week, Multi-center, Randomized Withdrawal Study of ampreloxetine in Treating Symptomatic Neurogenic Orthostatic Hypotension in Subjects with Primary Autonomic Failure

Read the 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 symptomatic nOH. The study consists of 3 periods: (i) 16-week open-label (OL) treatment with ampreloxetine, (ii) 6-week randomized placebo-controlled treatment, and (iii) 2-week follow-up (only for patients who do not enroll in Study 0171 (long-term extension safety study)).

Being tested
ampreloxetine, Placebo
Keywords
Symptomatic Neurogenic Orthostatic Hypotension, symptomatic nOH, multiple symptom atrophy, MSA, Parkinson's disease, PD, pure autonomic failure, PAF, orthostatic hypotension, OH, REDWOOD, ampreloxetine, low blood pressure, dizziness, fainting, blacking out, lightheadedness, norepinephrine, hypotension, Neurogenic Orthostatic Hypotension
Medical subject headings
Parkinson Disease, Pure Autonomic Failure, Hypotension, Orthostatic, Hypotension, Dizziness, Syncope, Parkinsonian Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ampreloxetineDrug

    Also called TD-9855

    Oral tablet, QD (Daily)

  • PlaceboDrug

    Oral tablet, QD

Study groups in NCT03829657
Study groupRoleWhat they receive
ampreloxetine (Open Label (OL))ExperimentalParticipants will receive ampreloxetine as a single, oral, daily dose of active drug for 16 weeks.
Receives: Drug: ampreloxetine
ampreloxetineExperimentalAfter completing the OL, participants randomized to ampreloxetine will receive single, oral, daily dose of active drug for a further 6 weeks.
Receives: Drug: ampreloxetine
PlaceboPlacebo comparatorAfter completing the OL, participants randomized to Placebo will receive single, oral, daily dose of placebo for 6 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Participants With Treatment Failure at Week 6 of RW Treatment Period

    Treatment failure was defined as proportion of participants who met the following criteria at Week 6 following randomization: Change (worsening) from baseline in Question 1 of the Orthostatic Hypotension Symptom Assessment (OHSA#1) score of 1.0 point and worsening of disease severity as assessed by a 1-point change in Patient Global Impression of Severity (PGI-S). OHSA Question #1 assessed dizziness, lightheadedness, feeling faint, or feeling like you might blackout. PGI-S assessed patient's impression of disease severity.

    Least squares mean here is the model-based proportion of participants with treatment failure using logistic regression.

    Measured: 6-week randomized withdrawal period (Week 16 to Week 22)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2019
  2. Study start22 Feb 2019
  3. Primary completion10 Nov 2021
  4. Study completion10 Nov 2021

Why it stopped: Stopped early due to company decision. Company decision based on analysis results in TD-9855-0169.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Open Label Extension followed by Randomized Parallel Assignment
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
203 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03829657
Sponsor's protocol ID
0170
Other IDs
2018-003941-41, 2018
Acronym
REDWOOD
Status last verified
Dec 2022
First submitted
10 Jan 2019
Last updated
20 Jan 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

Publications

  • Freeman R, Kaufmann H, Biaggioni I, Iodice V, Jordan J, Vickery R, Geurin T, Kmiecik MJ, Norcliffe-Kaufmann L. Mechanism-Based Therapy With Ampreloxetine for Neurogenic Orthostatic Hypotension in Multiple System Atrophy: A Randomized Withdrawal Trial. Neurology. 2026 Aug 11;107(3):e218284. doi: 10.1212/WNL.0000000000218284. Epub 2026 Jul 20.

    PubMed 42475649

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ampreloxetine in people with Symptomatic Neurogenic Orthostatic Hypotension and MSA, run by Theravance Biopharma at 82 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 82 sites in United States, Italy, United Kingdom, Poland, Russia and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants With Treatment Failure at Week 6 of RW Treatment Period (time frame: 6-week randomized withdrawal period (Week 16 to Week 22)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03829657, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2023.

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REDWOOD Clinical Trial NCT03829657 | AzTrials