Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure

NCT03750552 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 01692018-003289-15
• Study Type: interventional
• Target: 195
• Locations: 17 countries
• Sites: 117

Brief Summary

A Phase 3 study to evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in subjects with primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH with up to 4 weeks of treatment.

Conditions

Symptomatic Neurogenic Orthostatic Hypotension

Keywords

Symptomatic Neurogenic Orthostatic Hypotension; symptomatic nOH; multiple system atrophy; MSA; Parkinson's disease; PD; pure autonomic failure; PAF; primary autonomic failure; SEQUOIA; ampreloxetine; low blood pressure; dizziness; fainting; blacking out; lightheadedness; norepinephrine; hypotension; Parkinsonism; TD-9855; Neurogenic Orthostatic Hypotension; nOH; 0145; 145; 169; 0169; TD9855

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 Score at Week 4

  OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale where each question uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference. Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout. A mean negative change from baseline indicates a better outcome.

  Baseline and Week 4

Secondary Outcomes (4)

• Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score at Week 4

  Baseline and Week 4

• Change From Baseline in Orthostatic Hypotension Daily Activities Scale (OHDAS) Composite Score at Week 4

  Baseline and Week 4

• Number of Participants Who Experienced an Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Week 4

  Baseline and Week 4

• Number of Participants Who Experienced at Least One Fall

  Up to Week 4

Study Arms (2)

ampreloxetine

EXPERIMENTAL

Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.

Drug: ampreloxetine

Placebo

PLACEBO COMPARATOR

Participants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks.

Drug: Placebo

Interventions

ampreloxetine DRUG

Oral tablet, QD

Also known as: TD-9855

ampreloxetine

Placebo DRUG

Oral tablet, QD

Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 minutes of being tilted-up to ≥60o from a supine position as determined by a tilt-table test.
• Subject must score at least a 4 on the Orthostatic Hypotension Symptom Assessment Question #1 at randomization visit.
• 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).
• 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 NE levels \>100 pg/mL after being in seated position for 30 minutes.

You may not qualify if:

• 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 SNRIs.
• Subject currently uses concomitant antihypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction.
• Subject has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half-lives, whichever is longer, prior to randomization 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 a known or suspected alcohol or substance abuse within the past 12 months (DSM-IV-TR® definition of alcohol or substance abuse).
• Subject has a clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months.
• Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to randomization.
• 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 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 findings (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/1.73m2, or any abnormal laboratory value that could interfere with safety of the subject).

Sponsors & Collaborators

• Theravance Biopharma: lead

Study Sites (125)

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

Collaborative Neuroscience Network, LLC

Long Beach, California, 90806, United States

Location

Stanford Neuroscience Health Center

Palo Alto, California, 94304, United States

Location

Colorado Springs Neurological Associates, PC

Colorado Springs, Colorado, 80907, United States

Location

University of Colorado Health

Loveland, Colorado, 80538, United States

Location

Georgetown University Hospital, Dept. of Neurology

Washington D.C., District of Columbia, 20007, United States

Location

Parkinson's Disease and Movement Disorders Center

Boca Raton, Florida, 33486, United States

Location

SFM Clinical Research

Boca Raton, Florida, 33487, United States

Location

Fixel Institute for Neurological Diseases

Gainesville, Florida, 32608, United States

Location

Neurostudies, Inc

Port Charlotte, Florida, 33952, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

NorthShore University Health System

Glenview, Illinois, 60026, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Rutgers New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Georgetown University Hospital

McLean, Virginia, 22101, United States

Location

Inland Northwest Research

Spokane, Washington, 99202, United States

Location

Concord Hospital

Concord, New South Wales, 2139, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Monash Health - Clinical Trials Centre

Clayton, Victoria, 3168, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Perron Institute for Neurological and Translational Science, QEII Medical Centre

Nedlands, 6009, Australia

Location

Medizinische Universitat Innsbruck Abteilung Fur Neurologie

Innsbruck, 6020, Austria

Location

Universitätsklinikum Tulln

Tulln, 3430, Austria

Location

Wilhelminenspital Wien Abteilung fur Neurologie

Vienna, 1160, Austria

Location

UMHAT Sveti Georgi EAD Clinic of Neurological Diseases

Plovdiv, 4000, Bulgaria

Location

MHATNP Sv.Naum, EAD

Sofia, 1113, Bulgaria

Location

UMHAT Alexandrovska EAD Clinic of Neurological Diseases

Sofia, 1431, Bulgaria

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

London Health Sciences Centre-CCIT

London, Ontario, N6A 5A5, Canada

Location

University Health Network - Toronto Western Hospital Movement Disorders Clinic

Toronto, Ontario, M5T 2S8, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

Bispebjerg og Frederiksberg Hospital

Copenhagen, 2400, Denmark

Location

Odense Universitetshospital

Odense, 5000, Denmark

Location

East Tallinn Central Hospital

Tallinn, 10138, Estonia

Location

Astra Team Clinic

Tallinn, 11315, Estonia

Location

Tartu University Hospital

Tartu, 50406, Estonia

Location

Hopital Roger Salengro - CHU Lille

Lille, Nord, France

Location

CHU Caremeau

Nîmes, 30029, France

Location

Hospital Pierre Paul Rquet, CHU Purpan

Toulouse, 31059, France

Location

Universitaetsklinikum Freiburg - Klinik fur Neurologie und Neurophysiologie

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Gemeinschaftspraxis Dr. med. J. Springub/ W. Schwarz

Westerstede, Lower Saxony, 26655, Germany

Location

Praxis Dr. Oehlwein

Gera, Thuringia, 07551, Germany

Location

Charite Universitatsmedizin Berlin - Campus Benjamin Franklin

Berlin, 12 203, Germany

Location

Alexianer St. Joseph-Krankenhaus Berlin-Weißensee, Klinik für Neurologie

Berlin, 13088, Germany

Location

Charite - Campus Virchow-Klinikum, Klinik fur Neurologie

Berlin, 13353, Germany

Location

Charite - Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Clinexpert Kft.

Budapest, 1033, Hungary

Location

Semmelweis Egyetem

Budapest, 1083, Hungary

Location

Pecsi Tudomanyegyetem, Neurologiai Klinika

Pécs, 7623, Hungary

Location

Szent Borbala Korhaz

Tatabánya, 2800, Hungary

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Kaplan Medical Center

Rehovot, 7610001, Israel

Location

Ziv Medical Center

Safed, 1311001, Israel

Location

Tel Aviv Medical Center

Tel Aviv, 6423906, Israel

Location

Chaim Sheba Medical Center

Tel Litwinsky, 5262101, Israel

Location

Istituto Clinico Humanitas - IRCCS

Rozzano, Milano, 20089, Italy

Location

Fondazione Istituto G.Giglio di Cefalù

Cefalù, Palermo, 90015, Italy

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona Umberto I - G.M. Lancisi - G. Salesi, SOD Clinica di Neuroriabilitazione

Ancona, 60126, Italy

Location

Universita di Bologna-Clinica Neurologica-Dipartimento di Scienze Neurologiche Ospedale Bellaria

Bologna, 40139, Italy

Location

Azienda Ospedaliero - Universitaria Policlinico Vittorio Emanuele. - P.O G. Rodolico, Clinica Neurologica

Catania, 95123, Italy

Location

Universita Gabriele D'Annunzio- Cesi-Met

Chieti, 66100, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Ospedale San Raffaele I U.O. di Neurologia

Milan, 58-20132, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

Fondazione PTV - Policlinico Tor Vergata I U.O.C. Neurologia

Roma, 00133, Italy

Location

Ospedale San Giovanni Battista del Sovrano Militare Ordine di Malta

Roma, 00148, Italy

Location

Ospedale San Giovanni Battista

Roma, 00148, Italy

Location

Policlinico Umberto I - Universita degli Studi di Roma La Sapienza / Neurologia

Roma, 00161, Italy

Location

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

Roma, 00168, Italy

Location

Sapienza University of Rome

Roma, 00185, Italy

Location

AOU San Giovanni di Dio e Ruggi d'Aragona

Salerno, 84131, Italy

Location

A.O. Santa Maria

Terni, 5100, Italy

Location

New Zealand Brain Research Institute

Christchurch, 8011, New Zealand

Location

Specjalistyczna Praktyka Lekarska prof.Grzegorz Opala

Katowice, 40-588, Poland

Location

PRATIA MCM Kraków

Krakow, 30-510, Poland

Location

Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej

Krakow, 31-505, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie

Lublin, 20-954, Poland

Location

Instytut Zdrowia dr Boczarska-Jedynak

Oświęcim, 32-600, Poland

Location

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

Siemianowice Śląskie, 41-100, Poland

Location

ETG Warszawa

Warsaw, 02-777, Poland

Location

Specjalistyczne Gabinety sp. z o.o.

Warsaw, 30-539, Poland

Location

Hospital Senhora da Oliveira - Guimaraes, EPE

Guimarães, 4835-044, Portugal

Location

Centro Hospitalar e Universitario Lisboa Norte - Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Campus Neurologico Senior

Torres Vedras, 2560-280, Portugal

Location

State Autonomous Institution of Healthcare Republican Clinical Hospital of the Ministry of Healthcare of Republic Tatarstan

Kazan', Tatarstan Republic, 420064, Russia

Location

Federal State Budgetary Institution Federal Sibirian Scientific and Clinical Center of Federal Medico-Biological Agency

Krasnoyarsk, 660037, Russia

Location

Federal State Budgetary Educational Institution of Additional Professional Education Russian Medical Academy of Continuous Postgraduate Education of the Ministry of Healthcare of the Russian Federation

Moscow, 125284, Russia

Location

NHI Central Clinical Hospital #2 of JSC Russian Railways N.A. Semashko

Moscow, 129128, Russia

Location

City Neurological Center Sibneiromed

Novosibirsk, 630091, Russia

Location

SBEIHPE Novosibirsk State Medical University

Novosibirsk, 630091, Russia

Location

Federal State Budgetary Institution National Medical Research Centre of psychiatry and neurology named after V.M. Bekhterev of the Ministry of Healthcare of the Russian Federation

Saint Petersburg, 192019, Russia

Location

Human Brain Institute RAMS

Saint Petersburg, 197376, Russia

Location

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

Saint Petersburg, 197706, Russia

Location

Regional State Budgetary Institution of Healthcare Smolensk Regional Clinical Hospital

Smolensk, 214018, Russia

Location

Hospital Universitario Donostia

San Sebastián, Guipuzcoa, 20014, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Navarrabiomed Fundacion Miguel Servet

Pamplona, Navarre, 31008, Spain

Location

Hospital de Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Mutua de Terrasa

Barcelona, 08222, Spain

Location

Hospital Universitario Puerta del Mar

Cadiz, 11009, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Communal Institution Dnipropetrovsk I.I.Mechnikov RCH

Dnipro, 49005, Ukraine

Location

Communal Noncommercial Enterprise City Policlinic #9 of Kharkiv City Council

Kharkiv, 61172, Ukraine

Location

Communal Noncommercial Enterprise of Lviv Regional Council Lviv Regional Clinical Hospital Dept of Neurology

Lviv, 79010, Ukraine

Location

CNE Acad O.I. Yushchenko Vinnytsia Reg Psychoneurological Hospital of Vinnytsia Regional Council, Department of Neurology

Vinnytsia, 21005, Ukraine

Location

Communal Institution City Clinical Hospital #6

Zaporizhzhia, 69035, Ukraine

Location

Royal Devon and Exeter Hospital

Exeter, Devon, EX2 5DW, United Kingdom

Location

Re:Cognition Health

Plymouth, Devon, PL6 8BT, United Kingdom

Location

Barts Hospital

London, Greater London, EC1A 7BE, United Kingdom

Location

The National Hospital for Neurology & Neurosurgery

London, Greater London, WC1N 3BG, United Kingdom

Location

King's College Hospital

London, Manchester, SES 9PJ, United Kingdom

Location

Re:Cognition Health Ltd

Birmingham, West Midlands, B16 8LT, United Kingdom

Location

Re:Cognition Health

London, W1G 9JF, United Kingdom

Location

Salford Royal

Salford, M6 8HD, United Kingdom

Location

MeSH Terms

Conditions

Multiple System Atrophy; Parkinson Disease; Pure Autonomic Failure; Hypotension; Dizziness; Syncope; Parkinsonian Disorders

Interventions

ampreloxetine

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Vascular Diseases; Cardiovascular Diseases; Sensation Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations

Results Point of Contact

• Title: Medical Monitor
• Organization: Theravance Biopharma Inc

medinfo@theravance.com

1-855-633-8479

Study Officials

• Medical Monitor

  Theravance Biopharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel assignment

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: November 23, 2018
• Study Start: January 24, 2019
• Primary Completion: July 21, 2021
• Study Completion: July 21, 2021
• Last Updated: September 14, 2022
• Results First Posted: September 14, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7); NZ (1); HU (4); UA (5); AU (3); IT (17); GB (8); DK (2); ES (11); BU (3); US (23); CA (4); FR (3); PT (3); RU (10); IL (5); PL (8)