Clinical trial NCT02586623: Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension
Official title: RESTORE: A Clinical Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension to Assess Sustained Effects of Droxidopa Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Symptomatic Neurogenic Orthostatic Hypotension
Keywords: Parkinson's Disease
Multiple System Atrophy
Pure Autonomic Failure
Primary Autonomic Failure
Dopamine Beta Hydroxylase Deficiency
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2015-10-26
Enrollment: 453
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the time to treatment intervention in patients with Parkinson's Disease (PD), Multiple System Atrophy (MSA), Pure Autonomic Failure (PAF), Non-Diabetic Autonomic Neuropathy (NDAN) or Dopamine Beta Hydroxylase (DBH) Deficiency who have been previously stabilized with droxidopa therapy for symptoms of neurogenic orthostatic hypotension (NOH) (dizziness, light-headedness, or feelings that they are about to black out)

Detailed description: This is a multi-site, placebo-controlled, double-blind, randomized withdrawal, time to intervention study with a duration of up to 36 weeks, consisting of 5 periods:

Screening Period: up to 4 weeks duration; Open-Label Titration Period (Titration Period): up to 4 weeks duration; Open-Label Treatment Period (Open-Label Period): 12 weeks duration; Double-Blind Treatment Period (Double-Blind Period): 12 weeks duration; Safety Follow-Up Period: 4 weeks duration

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

Primary outcomes:
measure: Time To Intervention
timeFrame: Randomization (Day 0) up to Week 12
Secondary outcomes:
measure: Number of Participants Who Needed Intervention During the 12-week Double-Blind Treatment Period
timeFrame: Randomization (Day 0) up to Week 12
measure: Time To All-cause Discontinuation
timeFrame: Randomization (Day 0) up to Week 12
measure: Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score
timeFrame: Randomization (Day 0); Weeks 2 to 12
measure: Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score
timeFrame: Randomization (Day 0); Weeks 2 to 12
measure: Clinician-rated Clinical Global Impressions - Severity (CGI-S)
timeFrame: Weeks 2 to 12
measure: Participant-rated CGI-S
timeFrame: Weeks 2 to 12
Other outcomes:
Locations:
city: Chandler
country: United States
facility: MDFirst Research - Chandler
state: Arizona
city: Phoenix
country: United States
facility: 21st Century Neurology
state: Arizona
city: Scottsdale
country: United States
facility: Movement Disorders Center of Arizona
state: Arizona
city: Tucson
country: United States
facility: Center For Neurosciences
state: Arizona
city: Tucson
country: United States
facility: Movement Disorder Clinic - The University of Arizona
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Health Sciences Center, Department Of Neurology
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Cardiology Clinic
state: Arkansas
city: Berkeley
country: United States
facility: East Bay Physicians Medical Group
state: California
city: Berkeley
country: United States
facility: Sutter East Bay Medical Foundation
state: California
city: Fountain Valley
country: United States
facility: The Parkinson's and Movement Disorder Institute
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists, LLC
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: University Of Southern California
state: California
city: Mountain View
country: United States
facility: Parkinson's Institute and Clinical Center
state: California
city: Oxnard
country: United States
facility: Diverse Research Solutions, LLC
state: California
city: Oxnard
country: United States
facility: Focilmed
state: California
city: Palo Alto
country: United States
facility: Parkinsons Disease & Movement Disorder of Silicon Valley
state: California
city: Pasadena
country: United States
facility: Neurosearch, Inc. - Pasedena
state: California
city: Pasadena
country: United States
facility: Neurosearch, Inc. - Ventura
state: California
city: Pasadena
country: United States
facility: SC3 Research Group
state: California
city: Reseda
country: United States
facility: Neurosearch, Inc. - Reseda
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento
state: California
city: Sacramento
country: United States
facility: Sutter Neuroscience
state: California
city: Sunnyvale
country: United States
facility: The Parkinson's Institute and Clinical Center
state: California
city: Torrance
country: United States
facility: Neurosearch Inc. - Torrance
state: California
city: Colorado Springs
country: United States
facility: Colorado Springs Neurological Associates
state: Colorado
city: Danbury
country: United States
facility: Associated Neurologists, P.C.
state: Connecticut
city: Fairfield
country: United States
facility: Associated Neurologists of Southern Connecticut, P.C.
state: Connecticut
city: Manchester
country: United States
facility: Eastern Connecticut Neurology Specialists, LLC
state: Connecticut
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale Neurology / Hypertension Program
state: Connecticut
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Neurology Specialists
state: Delaware
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: MedStar Georgetown-MedStar Georgetown Transplant Institute University Hospital (MGUH)
state: District of Columbia
city: Boca Raton
country: United States
facility: Neurology Offices Of South Florida
state: Florida
city: Boca Raton
country: United States
facility: Parkinson's Disease And Movement Disorders Center of Boca Raton
state: Florida
city: Boca Raton
country: United States
facility: South Florida Neurology Associates, P.A.
state: Florida
city: Clearwater
country: United States
facility: Innovative Research of West Florida
state: Florida
city: Gainesville
country: United States
facility: UF Center for Movement Disorders and Neurorestoration
state: Florida
city: Hialeah
country: United States
facility: Galiz Research
state: Florida
city: Kissimmee
country: United States
facility: SIH Research
state: Florida
city: Maitland
country: United States
facility: Neurology Associates
state: Florida
city: Miami Gardens
country: United States
facility: Pro-Care Research Center, Corporation
state: Florida
city: Miami Lakes
country: United States
facility: New Life Medical Research Center
state: Florida
city: Miami
country: United States
facility: Future Clinical Research
state: Florida
city: Miami
country: United States
facility: Project 4 Research
state: Florida
city: Miami
country: United States
facility: Premium Medical Research, Corp
state: Florida
city: Miami
country: United States
facility: University Of Miami - Jackson Memorial Hospital, Dept. of Neurology
state: Florida
city: Miami
country: United States
facility: Coral Way Research
state: Florida
city: Miami
country: United States
facility: Florida Research Center
state: Florida
city: Miami
country: United States
facility: Anchor Medical Research, LLC
state: Florida
city: Miami
country: United States
facility: Novel Clinical Research Center, LLC
state: Florida
city: Port Charlotte
country: United States
facility: Neurostudies, Inc.
state: Florida
city: Port Charlotte
country: United States
facility: Parkinson's Disease Treatment Center of Southwest Florida
state: Florida
city: Tampa
country: United States
facility: Eminance Medical & Clinical Research
state: Florida
city: Tampa
country: United States
facility: University Of South Florida
state: Florida
city: Tampa
country: United States
facility: USF Parkinson's & Movement Disorders Center
state: Florida
city: Vero Beach
country: United States
facility: Vero Neurology
state: Florida
city: Vero Beach
country: United States
facility: Geodyssey Research, LLC
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Gainesville
country: United States
facility: Neurological Center of North Georgia
state: Georgia
city: Gainesville
country: United States
facility: The Neurological Center of North Georgia
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Medical Group
state: Illinois
city: Chicago
country: United States
facility: Cardio Specialists Group, Ltd., Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center - Department Of Cardiology
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center, Department of Neurology
state: Illinois
city: Glenview
country: United States
facility: NorthShore Neurological Institute
state: Illinois
city: Winfield
country: United States
facility: Central Dupage Hospital
state: Illinois
city: Winfield
country: United States
facility: Northwestern Medicine Central DuPage Hospital
state: Illinois
city: Avon
country: United States
facility: American Health Network of Indiana
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan Physician Network Indiana Heart Physicians
state: Indiana
city: Kansas City
country: United States
facility: Mid America Cardiology - University of Kansas
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Covington
country: United States
facility: Louisiana Heart Center
state: Louisiana
city: Scarborough
country: United States
facility: Maine Medical Partners Technology
state: Maine
city: Hagerstown
country: United States
facility: Mir Neurology
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital - Movement Disorders Clinic
state: Massachusetts
city: Boston
country: United States
facility: Movement Disorders Clinic
state: Massachusetts
city: Boston
country: United States
facility: Autonomic and Movement Disorders
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Faulkner Hospital (BWFH) - Brigham & Women's Foot & Ankle Center
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University, Department of Neurology
state: Michigan
city: Farmington Hills
country: United States
facility: Detroit Clinical Research Center
state: Michigan
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research
state: Michigan
city: Traverse City
country: United States
facility: Northern Michigan Neurology
state: Michigan
city: Traverse City
country: United States
facility: Nothern Michigan Neurology
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford West Bloomfield Hospital
state: Michigan
city: Kearney
country: United States
facility: Platte Valley Medical Group
state: Nebraska
city: Omaha
country: United States
facility: Methodist Physicians Clinic - Heart Consultants
state: Nebraska
city: Omaha
country: United States
facility: MPC Heart Consultants
state: Nebraska
city: Omaha
country: United States
facility: University Of Nebraska Medical Center
state: Nebraska
city: Omaha
country: United States
facility: The Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Edison
country: United States
facility: JFK Neuroscience Institution
state: New Jersey
city: Toms River
country: United States
facility: Neuroscience Research Institute, LLC
state: New Jersey
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Commack
country: United States
facility: David L. Kreitzman MD, PC
state: New York
city: Commack
country: United States
facility: Office of David L. Kreitzman, M.D., P.C.
state: New York
city: Hawthorne
country: United States
facility: Neurology Associates of West Chester
state: New York
city: New Hyde Park
country: United States
facility: Parker Jewish Institute for Health Care & Rehabilitation
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College, Dept. of Neurology
state: New York
city: New York
country: United States
facility: The Bendheim Parkinson and Movement Disorders Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Project 4 Research, Inc., The Neurological Institute at Columbia University Medical Center
state: New York
city: New York
country: United States
facility: The Neurological Institute at Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Parker Jewish Institute For Healthcare And Rehabilitation
state: New York
city: Plainview
country: United States
facility: Island Neurological Associates
state: New York
city: Staten Island
country: United States
facility: Alpha Neurology
state: New York
city: West Haverstraw
country: United States
facility: Helen Hayes Hospital
state: New York
city: Williamsville
country: United States
facility: UBMD Neurology
state: New York
city: Apex
country: United States
facility: Peak Clinical Trials
state: North Carolina
city: Charlotte
country: United States
facility: The Neurological Institute, PA
state: North Carolina
city: Charlotte
country: United States
facility: Neurosciences Institute
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas HealthCare System Neurosciences Institute
state: North Carolina
city: Bellevue
country: United States
facility: Insight Neuroscience, LLC
state: Ohio
city: Centerville
country: United States
facility: Dayton Center for Neurological Disorders
state: Ohio
city: Cincinnati
country: United States
facility: Riverhills Healthcare, Inc.
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic - Taussig Cancer Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio Health Research Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State University, Department of Neurology
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Toledo
country: United States
facility: Gardner-McMaster Parkinson Center - The University of Toledo
state: Ohio
city: Toledo
country: United States
facility: Medical College of Ohio, Department of Neurology
state: Ohio
city: Ardmore
country: United States
facility: Baha Abu-Esheh, MD
state: Oklahoma
city: Ardmore
country: United States
facility: CardioVoyage, LLC
state: Oklahoma
city: Oklahoma City
country: United States
facility: COR Clinical Research, LLC
state: Oklahoma
city: Portland
country: United States
facility: Legacy / Oregon Clinic Neurology
state: Oregon
city: Portland
country: United States
facility: The Oregon Clinic
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Neurology Associates
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Children's Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel Neurosciences Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania, Parkinson's Disease & Movement Disorders Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Department of Neurology
state: Pennsylvania
city: Providence
country: United States
facility: Dr. Umer Akbar MD, Office of
state: Rhode Island
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Autonomic Dysfunction Center - Clinical Trials Center
state: Tennessee
city: Carrollton
country: United States
facility: iMD Medical Center
state: Texas
city: Carrollton
country: United States
facility: Sunbeam Clinical Research
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Greenville
country: United States
facility: Elite Primary Care
state: Texas
city: Greenville
country: United States
facility: Sunbeam Clinical Research
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: McKinney
country: United States
facility: Texas Institute of Cardiology, The Heartbeat Clinic
state: Texas
city: McKinney
country: United States
facility: The Heartbeat Clinic
state: Texas
city: Prosper
country: United States
facility: Sunbeam Clinical Research, LLC.
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: Tyler
country: United States
facility: Christus Research Institute
state: Texas
city: Webster
country: United States
facility: Clear Lake Specialties
state: Texas
city: Salt Lake City
country: United States
facility: Bateman Home Center
state: Utah
city: Alexandria
country: United States
facility: Inova Health Systems
state: Virginia
city: Falls Church
country: United States
facility: Integrated Neurology Services, PLLC
state: Virginia
city: Norfolk
country: United States
facility: Health Research of Hampton Roads-Norfolk, Inc
state: Virginia
city: Norfolk
country: United States
facility: Sentara Neurology Specialists
state: Virginia
city: Richmond
country: United States
facility: Henrico Doctors Neurology Associates, LLC
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: Kirkland
country: United States
facility: Booth Gardner Parkinson's Care Center
state: Washington
city: Spokane
country: United States
facility: Northwest Neurology, Premier Clinical Research
state: Washington
city: Spokane
country: United States
facility: Premeir Clinical Research
state: Washington
city: Grafton
country: United States
facility: Aurora Medical Center
state: Wisconsin
city: Grafton
country: United States
facility: Grafton Medical Office
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Department of Neurology
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Sinai Medical Center-Arrhythmia Center
state: Wisconsin
Study officials:
affiliation: LundbeckClinicalTrials@Lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: Hauser RA, Favit A, Hewitt LA, Lindsten A, Gorny S, Kymes S, Isaacson SH. Durability of the Clinical Benefit of Droxidopa for Neurogenic Orthostatic Hypotension During 12 Weeks of Open-Label Treatment. Neurol Ther. 2022 Mar;11(1):459-469. doi: 10.1007/s40120-021-00317-5. Epub 2022 Feb 2.