Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension (RESTORE)
Symptomatic Neurogenic Orthostatic Hypotension
About this trial
This is an interventional treatment trial for Symptomatic Neurogenic Orthostatic Hypotension focused on measuring Parkinson's Disease, Multiple System Atrophy, Pure Autonomic Failure, Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency
Eligibility Criteria
Inclusion Criteria:
- 18 years or older and able to stand (with or without limited assistance)
- Clinical diagnosis of symptomatic orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA or PAF) or NDAN or DBH Deficiency
- Score of at least 4 or greater on Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 (measured at Screening [Visit 1] and the first Titration Visit [Visit 2a] prior to dosing)
- A documented drop of at least 20 millimeters of mercury (mmHg) in SBP, within 3 minutes of standing. This can either be documented in the patient history or assessed during Screening prior to the first Titration Visit (Visit 2a)
- Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care
Additional inclusion criteria for patients taking prescribed droxidopa prior to study entry:
Patients who are taking prescribed droxidopa therapy are eligible to participate in the study if they meet the other inclusion criteria and also have been on a stable dose of prescribed droxidopa for at least 2 weeks prior to the Screening Visit (Visit 1). In addition, they must meet either of the following at the Screening Visit (Visit 1):
- The patient's Visit 1 OHSA Item #1 score is ≥ 7 AND the prescribed dose is ≤ 300 mg three times daily (TID); OR
- The patient's Visit 1 OHSA Item #1 score is ≤6 AND worsens by ≥ 2 units when retested after washing out of droxidopa for at least 3 days
Exclusion Criteria:
- In the investigator's opinion, the patient is not able to understand or cooperate with study procedures
- Known or suspected alcohol or substance use disorder within the past 12 months (DSM-5 criteria)
- Women who are pregnant or breastfeeding
- Women of childbearing potential (WOCP) who are not using at least one method of contraception with their partner
- Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg diastolic. Sustained is defined as the average of 3 observations each at least 10 minutes apart with the patient having been supine and at rest for at least 5 minutes prior to each measurement.
- Untreated closed angle glaucoma
- Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine hypertension are allowed in this study)
- Any significant uncontrolled cardiac arrhythmia
- History of myocardial infarction or stroke, within the past 2 years
- Current unstable angina
- Congestive heart failure (NYHA Class 3 or 4)
- Diabetic autonomic neuropathy
- History of cancer within the past 2 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ
- Any major surgical procedure within the past 30 days
- Currently receiving any investigational drug or have received an investigational drug within the past 28 days
Additional protocol defined exclusion criteria do apply
Sites / Locations
- MDFirst Research - Chandler
- 21st Century Neurology
- Movement Disorders Center of Arizona
- Center For Neurosciences
- Movement Disorder Clinic - The University of Arizona
- University of Arizona Health Sciences Center, Department Of Neurology
- Arkansas Cardiology Clinic
- East Bay Physicians Medical Group
- Sutter East Bay Medical Foundation
- The Parkinson's and Movement Disorder Institute
- Behavioral Research Specialists, LLC
- Loma Linda University Medical Center
- University Of Southern California
- Parkinson's Institute and Clinical Center
- Diverse Research Solutions, LLC
- Focilmed
- Parkinsons Disease & Movement Disorder of Silicon Valley
- Neurosearch, Inc. - Pasedena
- Neurosearch, Inc. - Ventura
- SC3 Research Group
- Neurosearch, Inc. - Reseda
- Radiological Associates of Sacramento
- Sutter Neuroscience
- The Parkinson's Institute and Clinical Center
- Neurosearch Inc. - Torrance
- Colorado Springs Neurological Associates
- Associated Neurologists, P.C.
- Associated Neurologists of Southern Connecticut, P.C.
- Eastern Connecticut Neurology Specialists, LLC
- Yale-New Haven Hospital
- Yale Neurology / Hypertension Program
- Yale University School Of Medicine
- Christiana Care Neurology Specialists
- Georgetown University
- MedStar Georgetown-MedStar Georgetown Transplant Institute University Hospital (MGUH)
- Neurology Offices Of South Florida
- Parkinson's Disease And Movement Disorders Center of Boca Raton
- South Florida Neurology Associates, P.A.
- Innovative Research of West Florida
- UF Center for Movement Disorders and Neurorestoration
- Galiz Research
- SIH Research
- Neurology Associates
- Pro-Care Research Center, Corporation
- New Life Medical Research Center
- Future Clinical Research
- Project 4 Research
- Premium Medical Research, Corp
- University Of Miami - Jackson Memorial Hospital, Dept. of Neurology
- Coral Way Research
- Florida Research Center
- Anchor Medical Research, LLC
- Novel Clinical Research Center, LLC
- Neurostudies, Inc.
- Parkinson's Disease Treatment Center of Southwest Florida
- Eminance Medical & Clinical Research
- University Of South Florida
- USF Parkinson's & Movement Disorders Center
- Vero Neurology
- Geodyssey Research, LLC
- Emory University
- Georgia Regents University
- Neurological Center of North Georgia
- The Neurological Center of North Georgia
- Hawaii Pacific Neuroscience
- Northwestern Medical Group
- Cardio Specialists Group, Ltd., Rush University Medical Center
- Rush University Medical Center - Department Of Cardiology
- Rush University Medical Center, Department of Neurology
- NorthShore Neurological Institute
- Central Dupage Hospital
- Northwestern Medicine Central DuPage Hospital
- American Health Network of Indiana
- Fort Wayne Neurological Center
- Franciscan Physician Network Indiana Heart Physicians
- Mid America Cardiology - University of Kansas
- University of Kansas Medical Center
- Louisiana Heart Center
- Maine Medical Partners Technology
- Mir Neurology
- Tufts Medical Center
- Massachusetts General Hospital - Movement Disorders Clinic
- Movement Disorders Clinic
- Autonomic and Movement Disorders
- Brigham and Women's Faulkner Hospital (BWFH) - Brigham & Women's Foot & Ankle Center
- Michigan State University, Department of Neurology
- Detroit Clinical Research Center
- Michigan Center of Medical Research
- Northern Michigan Neurology
- Nothern Michigan Neurology
- Henry Ford West Bloomfield Hospital
- Platte Valley Medical Group
- Methodist Physicians Clinic - Heart Consultants
- MPC Heart Consultants
- University Of Nebraska Medical Center
- The Nebraska Medical Center
- Dartmouth-Hitchcock Medical Center
- JFK Neuroscience Institution
- Neuroscience Research Institute, LLC
- SUNY Downstate Medical Center
- David L. Kreitzman MD, PC
- Office of David L. Kreitzman, M.D., P.C.
- Neurology Associates of West Chester
- Parker Jewish Institute for Health Care & Rehabilitation
- Weill Cornell Medical College, Dept. of Neurology
- The Bendheim Parkinson and Movement Disorders Center
- Columbia University Medical Center
- Project 4 Research, Inc., The Neurological Institute at Columbia University Medical Center
- The Neurological Institute at Columbia University Medical Center
- Parker Jewish Institute For Healthcare And Rehabilitation
- Island Neurological Associates
- Alpha Neurology
- Helen Hayes Hospital
- UBMD Neurology
- Peak Clinical Trials
- The Neurological Institute, PA
- Neurosciences Institute
- Carolinas HealthCare System Neurosciences Institute
- Insight Neuroscience, LLC
- Dayton Center for Neurological Disorders
- Riverhills Healthcare, Inc.
- Cleveland Clinic - Taussig Cancer Institute
- Ohio Health Research Institute
- Ohio State University, Department of Neurology
- The Ohio State University
- Gardner-McMaster Parkinson Center - The University of Toledo
- Medical College of Ohio, Department of Neurology
- Baha Abu-Esheh, MD
- CardioVoyage, LLC
- COR Clinical Research, LLC
- Legacy / Oregon Clinic Neurology
- The Oregon Clinic
- St. Luke's Neurology Associates
- Penn State Hershey Children's Hospital
- Penn State Milton S. Hershey Medical Center
- Drexel Neurosciences Institute
- University of Pennsylvania, Parkinson's Disease & Movement Disorders Center
- University of Pittsburgh, Department of Neurology
- Dr. Umer Akbar MD, Office of
- Rhode Island Hospital
- Vanderbilt University Autonomic Dysfunction Center - Clinical Trials Center
- iMD Medical Center
- Sunbeam Clinical Research
- UT Southwestern Medical Center
- Elite Primary Care
- Sunbeam Clinical Research
- University of Texas Health Science Center at Houston
- Texas Institute of Cardiology, The Heartbeat Clinic
- The Heartbeat Clinic
- Sunbeam Clinical Research, LLC.
- Central Texas Neurology Consultants
- Christus Research Institute
- Clear Lake Specialties
- Bateman Home Center
- Inova Health Systems
- Integrated Neurology Services, PLLC
- Health Research of Hampton Roads-Norfolk, Inc
- Sentara Neurology Specialists
- Henrico Doctors Neurology Associates, LLC
- Carilion Clinic
- Booth Gardner Parkinson's Care Center
- Northwest Neurology, Premier Clinical Research
- Premeir Clinical Research
- Aurora Medical Center
- Grafton Medical Office
- Aurora St. Luke's Medical Center
- Medical College of Wisconsin, Department of Neurology
- Aurora Sinai Medical Center-Arrhythmia Center
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Open Label Period
Randomized Period
Active droxidopa 100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally. During the Open Label Titration Period, patients will first receive 100 mg TID and their dose will be raised (in 100 mg increments) at subsequent visits until optimal dose is determined. During the Open Label Treatment Period, patients will receive active droxidopa100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally (equal to the patient's individual dose at the end of the Open-Label Titration Period).
Active droxidopa 100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally (equal to patients individual dose at the end of the Open-Label Period) or matching placebo.