Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure
- Conditions
- Symptomatic Neurogenic Orthostatic Hypotension
- Interventions
- Drug: Placebo
- Registration Number
- NCT03750552
- Lead Sponsor
- Theravance Biopharma
- 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.
- Detailed Description
A Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in subjects with primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH. The study consists of 3 periods: (i) 4-week screening, (ii) 4-week randomized treatment, and (iii) 2-week follow up. The trial utilizes an operational design featuring the ability to conduct protocol required visits as either in clinic or remote visits (except Screening visit).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 195
- 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.
-
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).
-
Subject has demonstrated a history of lifetime suicidal ideation and/or suicidal behavior, as outlined by the C-SSRS (Columbia Suicide Severity Rating Scale) (Baseline/Screening Version) subject should be assessed by the rater for risk of suicide and the subject's appropriateness for inclusion in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks. ampreloxetine ampreloxetine Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 Score at Week 4 Baseline and 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score at Week 4 Baseline and Week 4 OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale in which the composite score 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.
A mean negative change from baseline indicates a better outcome.Change From Baseline in Orthostatic Hypotension Daily Activities Scale (OHDAS) Composite Score at Week 4 Baseline and Week 4 OHDAS is an assessment of how low blood pressure symptoms affect daily life. OHDAS is a 4 item assessment in which the composite score 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.
A mean negative change from baseline indicates a better outcome.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 PGI-C was assessed using a 5-point scale where participants were asked to compare their current condition to their condition at baseline from 1 to 5, with 1 indicating the condition is very much improved and 5 indicating the condition is very much worse. These scores were analyzed in 2 categories: better and no change/worse.
Number of Participants Who Experienced at Least One Fall Up to Week 4
Trial Locations
- Locations (124)
Parkinson's Disease and Movement Disorders Center
🇺🇸Boca Raton, Florida, United States
NorthShore University Health System
🇺🇸Glenview, Illinois, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
University Health Network - Toronto Western Hospital Movement Disorders Clinic
🇨🇦Toronto, Ontario, Canada
UMHAT Sveti Georgi EAD Clinic of Neurological Diseases
🇧🇬Plovdiv, Bulgaria
MHATNP Sv.Naum, EAD
🇧🇬Sofia, Bulgaria
Clinexpert Kft.
🇭🇺Budapest, Hungary
Instytut Zdrowia dr Boczarska-Jedynak
🇵🇱Oświęcim, Poland
Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej
🇵🇱Kraków, Poland
Astra Team Clinic
🇪🇪Tallinn, Estonia
Hospital Senhora da Oliveira - Guimaraes, EPE
🇵🇹Guimaraes, Portugal
Hopital Roger Salengro - CHU Lille
🇫🇷Lille Cedex, Nord, France
Campus Neurologico Senior
🇵🇹Torres Vedras, Portugal
Bispebjerg og Frederiksberg Hospital
🇩🇰Copenhagen, Denmark
Odense Universitetshospital
🇩🇰Odense, Denmark
A.O. Santa Maria
🇮🇹Terni, Italy
Sapienza University of Rome
🇮🇹Roma, Italy
Collaborative Neuroscience Network, LLC
🇺🇸Long Beach, California, United States
Georgetown University Hospital, Dept. of Neurology
🇺🇸Washington, District of Columbia, United States
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Universita di Bologna-Clinica Neurologica-Dipartimento di Scienze Neurologiche Ospedale Bellaria
🇮🇹Bologna, Italy
CHU Caremeau
🇫🇷Nîmes, France
Azienda Ospedaliero - Universitaria Policlinico Vittorio Emanuele. - P.O G. Rodolico, Clinica Neurologica
🇮🇹Catania, Italy
Ospedale San Raffaele I U.O. di Neurologia
🇮🇹Milano, Italy
Hospital Pierre Paul Rquet, CHU Purpan
🇫🇷Toulouse, France
Universitaetsklinikum Freiburg - Klinik fur Neurologie und Neurophysiologie
🇩🇪Freiburg, Baden Wuerttemberg, Germany
Alexianer St. Joseph-Krankenhaus Berlin-Weißensee, Klinik für Neurologie
🇩🇪Berlin, Germany
Pecsi Tudomanyegyetem, Neurologiai Klinika
🇭🇺Pécs, Hungary
Fondazione Istituto G.Giglio di Cefalù
🇮🇹Cefalù, Palermo, Italy
Ospedale San Giovanni Battista
🇮🇹Roma, Italy
Charite - Campus Virchow-Klinikum, Klinik fur Neurologie
🇩🇪Berlin, Germany
Istituto Clinico Humanitas - IRCCS
🇮🇹Rozzano, Milano, Italy
Fondazione PTV - Policlinico Tor Vergata I U.O.C. Neurologia
🇮🇹Roma, Italy
Universita Gabriele D'Annunzio- Cesi-Met
🇮🇹Chieti, Italy
Szent Borbala Korhaz
🇭🇺Tatabanya, Hungary
PRATIA MCM Kraków
🇵🇱Kraków, Poland
Charite - Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Ospedale San Giovanni Battista del Sovrano Militare Ordine di Malta
🇮🇹Roma, Italy
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
NEURO-CARE Sp. z o.o. Sp. Komandytowa
🇵🇱Siemianowice Śląskie, Poland
Policlinico Umberto I - Universita degli Studi di Roma La Sapienza / Neurologia
🇮🇹Roma, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS / Istituto di Neurologia - Ambulatorio Disturbi del Movimento
🇮🇹Roma, Italy
City Neurological Center Sibneiromed
🇷🇺Novosibirsk, Russian Federation
SBEIHPE Novosibirsk State Medical University
🇷🇺Novosibirsk, Russian Federation
Specjalistyczna Praktyka Lekarska prof.Grzegorz Opala
🇵🇱Katowice, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
🇵🇱Lublin, Poland
Specjalistyczne Gabinety sp. z o.o.
🇵🇱Warszawa, Poland
Centro Hospitalar e Universitario Lisboa Norte - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Communal Institution Dnipropetrovsk I.I.Mechnikov RCH
🇺🇦Dnipro, Ukraine
Hospital Universitario Mutua de Terrasa
🇪🇸Barcelona, Spain
Hospital de Cruces
🇪🇸Barakaldo, Vizcaya, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario de La Princesa
🇪🇸Madrid, Spain
Hospital Universitario Puerta del Mar
🇪🇸Cadiz, Spain
Saint Petersburg State Budgetary Institution of Healthcare City Hospital # 40 of Kurortnyi Region
🇷🇺Saint Petersburg, Russian Federation
Royal Devon and Exeter Hospital
🇬🇧Exeter, Devon, United Kingdom
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Re:Cognition Health
🇬🇧London, United Kingdom
Salford Royal
🇬🇧Salford, United Kingdom
King's College Hospital
🇬🇧London, Manchester, United Kingdom
Barts Hospital
🇬🇧London, Greater London, United Kingdom
State Autonomous Institution of Healthcare Republican Clinical Hospital of the Ministry of Healthcare of Republic Tatarstan
🇷🇺Kazan, Tatarstan, Russian Federation
Gemeinschaftspraxis Dr. med. J. Springub/ W. Schwarz
🇩🇪Westerstede, Niedersachsen, Germany
Praxis Dr. Oehlwein
🇩🇪Gera, Thueringen, Germany
Rabin Medical Center
🇮🇱Petah Tikva, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Ziv Medical Center
🇮🇱Safed, Israel
Tel Aviv Medical Center
🇮🇱Tel Aviv, Israel
Colorado Springs Neurological Associates, PC
🇺🇸Colorado Springs, Colorado, United States
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Banner Sun Health Research Institute
🇺🇸Sun City, Arizona, United States
Stanford Neuroscience Health Center
🇺🇸Palo Alto, California, United States
University of Colorado Health
🇺🇸Loveland, Colorado, United States
Neurostudies, Inc
🇺🇸Port Charlotte, Florida, United States
SFM Clinical Research
🇺🇸Boca Raton, Florida, United States
Fixel Institute for Neurological Diseases
🇺🇸Gainesville, Florida, United States
Rutgers New Jersey Medical School
🇺🇸Newark, New Jersey, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
New York University Langone Health
🇺🇸New York, New York, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Concord Hospital
🇦🇺Concord, New South Wales, Australia
Inland Northwest Research
🇺🇸Spokane, Washington, United States
Medizinische Universitat Innsbruck Abteilung Fur Neurologie
🇦🇹Innsbruck, Austria
Monash Health - Clinical Trials Centre
🇦🇺Clayton, Victoria, Australia
Perron Institute for Neurological and Translational Science, QEII Medical Centre
🇦🇺Nedlands, Australia
Wilhelminenspital Wien Abteilung fur Neurologie
🇦🇹Wien, Austria
Universitätsklinikum Tulln
🇦🇹Tulln, Austria
UMHAT Alexandrovska EAD Clinic of Neurological Diseases
🇧🇬Sofia, Bulgaria
London Health Sciences Centre-CCIT
🇨🇦London, Ontario, Canada
Montreal Neurological Institute and Hospital
🇨🇦Montreal, Quebec, Canada
East Tallinn Central Hospital
🇪🇪Tallinn, Estonia
Tartu University Hospital
🇪🇪Tartu, Estonia
Chaim Sheba Medical Center
🇮🇱Tel HaShomer, Israel
Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona Umberto I - G.M. Lancisi - G. Salesi, SOD Clinica di Neuroriabilitazione
🇮🇹Ancona, Italy
AOU San Giovanni di Dio e Ruggi d'Aragona
🇮🇹Salerno, Italy
New Zealand Brain Research Institute
🇳🇿Christchurch, New Zealand
ETG Warszawa
🇵🇱Warszawa, Poland
NHI Central Clinical Hospital #2 of JSC Russian Railways N.A. Semashko
🇷🇺Moscow, Russian Federation
Federal State Budgetary Institution Federal Sibirian Scientific and Clinical Center of Federal Medico-Biological Agency
🇷🇺Krasnoyarsk, Russian Federation
Hospital Universitario Donostia
🇪🇸San Sebastián, Guipuzcoa, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Communal Noncommercial Enterprise of Lviv Regional Council Lviv Regional Clinical Hospital Dept of Neurology
🇺🇦Lviv, Ukraine
The National Hospital for Neurology & Neurosurgery
🇬🇧London, Greater London, United Kingdom
Re:Cognition Health Ltd
🇬🇧Birmingham, West Midlands, United Kingdom
The Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Georgetown University Hospital
🇺🇸McLean, Virginia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
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, Russian Federation
Charite Universitatsmedizin Berlin - Campus Benjamin Franklin
🇩🇪Berlin, Germany
University of Calgary
🇨🇦Calgary, Alberta, Canada
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, Russian Federation
Human Brain Institute RAMS
🇷🇺Saint Petersburg, Russian Federation
Regional State Budgetary Institution of Healthcare Smolensk Regional Clinical Hospital
🇷🇺Smolensk, Russian Federation
Communal Noncommercial Enterprise City Policlinic #9 of Kharkiv City Council
🇺🇦Kharkiv, Ukraine
CNE Acad O.I. Yushchenko Vinnytsia Reg Psychoneurological Hospital of Vinnytsia Regional Council, Department of Neurology
🇺🇦Vinnytsia, Ukraine
Communal Institution City Clinical Hospital #6
🇺🇦Zaporizhzhia, Ukraine
Navarrabiomed Fundacion Miguel Servet
🇪🇸Pamplona, Navarra, Spain
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States