Symptomatic Neurogenic Orthostatic HypotensionPhase 4RESTORENCT02586623
Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension
A Phase 4 study testing Droxidopa capsules in people with Symptomatic Neurogenic Orthostatic Hypotension, run by H. Lundbeck A/S at 168 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Symptomatic Neurogenic Orthostatic Hypotension
- What is being tested?
- Droxidopa capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 453 participants
- Where
- 168 sitesUnited States
- Study dates
- 11 Feb 2016to 9 Sep 2022
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
168 sites in 1 country.
168 sites in 1 country
United States168 sites
Inova Health Systems
Alexandria, Virginia, 22311
Peak Clinical Trials
Apex, North Carolina, 27502
Baha Abu-Esheh, MD
Ardmore, Oklahoma, 73401
CardioVoyage, LLC
Ardmore, Oklahoma, 73401
Emory University
Atlanta, Georgia, 30329
Georgia Regents University
Augusta, Georgia, 30912
American Health Network of Indiana
Avon, Indiana, 46123
Insight Neuroscience, LLC
Bellevue, Ohio, 44811
East Bay Physicians Medical Group
Berkeley, California, 94705
Sutter East Bay Medical Foundation
Berkeley, California, 94705
St. Luke's Neurology Associates
Bethlehem, Pennsylvania, 18018
Neurology Offices Of South Florida
Boca Raton, Florida, 33428
Parkinson's Disease And Movement Disorders Center of Boca Raton
Boca Raton, Florida, 33486
South Florida Neurology Associates, P.A.
Boca Raton, Florida, 33487
Tufts Medical Center
Boston, Massachusetts, 02111
Massachusetts General Hospital - Movement Disorders Clinic
Boston, Massachusetts, 02114
Movement Disorders Clinic
Boston, Massachusetts, 02114
Autonomic and Movement Disorders
Boston, Massachusetts, 02130
Brigham and Women's Faulkner Hospital (BWFH) - Brigham & Women's Foot & Ankle Center
Boston, Massachusetts, 02130
SUNY Downstate Medical Center
Brooklyn, New York, 11203
iMD Medical Center
Carrollton, Texas, 75006
Sunbeam Clinical Research
Carrollton, Texas, 75006
Dayton Center for Neurological Disorders
Centerville, Ohio, 45459
MDFirst Research - Chandler
Chandler, Arizona, 85226
The Neurological Institute, PA
Charlotte, North Carolina, 28204
Neurosciences Institute
Charlotte, North Carolina, 28205
Carolinas HealthCare System Neurosciences Institute
Charlotte, North Carolina, 28207
Northwestern Medical Group
Chicago, Illinois, 60611
Cardio Specialists Group, Ltd., Rush University Medical Center
Chicago, Illinois, 60612
Rush University Medical Center - Department Of Cardiology
Chicago, Illinois, 60612
Rush University Medical Center, Department of Neurology
Chicago, Illinois, 60612
Riverhills Healthcare, Inc.
Cincinnati, Ohio, 45219
Innovative Research of West Florida
Clearwater, Florida, 33756
Cleveland Clinic - Taussig Cancer Institute
Cleveland, Ohio, 44195
Colorado Springs Neurological Associates
Colorado Springs, Colorado, 80907
Ohio Health Research Institute
Columbus, Ohio, 43214
Ohio State University, Department of Neurology
Columbus, Ohio, 43221
The Ohio State University
Columbus, Ohio, 43221
David L. Kreitzman MD, PC
Commack, New York, 11725
Office of David L. Kreitzman, M.D., P.C.
Commack, New York, 11725
Louisiana Heart Center
Covington, Louisiana, 70433
UT Southwestern Medical Center
Dallas, Texas, 75390
Associated Neurologists, P.C.
Danbury, Connecticut, 06810
Michigan State University, Department of Neurology
East Lansing, Michigan, 48824
JFK Neuroscience Institution
Edison, New Jersey, 08220
Associated Neurologists of Southern Connecticut, P.C.
Fairfield, Connecticut, 06824
Integrated Neurology Services, PLLC
Falls Church, Virginia, 22043
Detroit Clinical Research Center
Farmington Hills, Michigan, 48334
Michigan Center of Medical Research
Farmington Hills, Michigan, 48334
Fort Wayne Neurological Center
Fort Wayne, Indiana, 46804
The Parkinson's and Movement Disorder Institute
Fountain Valley, California, 92708
UF Center for Movement Disorders and Neurorestoration
Gainesville, Florida, 32607
Neurological Center of North Georgia
Gainesville, Georgia, 30501
The Neurological Center of North Georgia
Gainesville, Georgia, 30501
Behavioral Research Specialists, LLC
Glendale, California, 91206
NorthShore Neurological Institute
Glenview, Illinois, 60026
Aurora Medical Center
Grafton, Wisconsin, 53024
Grafton Medical Office
Grafton, Wisconsin, 53024
Elite Primary Care
Greenville, Texas, 75401
Sunbeam Clinical Research
Greenville, Texas, 75401
Mir Neurology
Hagerstown, Maryland, 21740
Neurology Associates of West Chester
Hawthorne, New York, 10532
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, 17025
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Galiz Research
Hialeah, Florida, 33016
Hawaii Pacific Neuroscience
Honolulu, Hawaii, 96817
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Franciscan Physician Network Indiana Heart Physicians
Indianapolis, Indiana, 46237
Mid America Cardiology - University of Kansas
Kansas City, Kansas, 66160
University of Kansas Medical Center
Kansas City, Kansas, 66160
Platte Valley Medical Group
Kearney, Nebraska, 68845
Booth Gardner Parkinson's Care Center
Kirkland, Washington, 98034
SIH Research
Kissimmee, Florida, 34759
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Arkansas Cardiology Clinic
Little Rock, Arkansas, 72205
Loma Linda University Medical Center
Loma Linda, California, 92354
University Of Southern California
Los Angeles, California, 90033
Neurology Associates
Maitland, Florida, 32751
Eastern Connecticut Neurology Specialists, LLC
Manchester, Connecticut, 06040
Texas Institute of Cardiology, The Heartbeat Clinic
McKinney, Texas, 75069
The Heartbeat Clinic
McKinney, Texas, 75069
Future Clinical Research
Miami, Florida, 33122
Project 4 Research
Miami, Florida, 33125
Premium Medical Research, Corp
Miami, Florida, 33126
University Of Miami - Jackson Memorial Hospital, Dept. of Neurology
Miami, Florida, 33136
Coral Way Research
Miami, Florida, 33155
Florida Research Center
Miami, Florida, 33174
Anchor Medical Research, LLC
Miami, Florida, 33176
Novel Clinical Research Center, LLC
Miami, Florida, 33186
Pro-Care Research Center, Corporation
Miami Gardens, Florida, 33014
New Life Medical Research Center
Miami Lakes, Florida, 33014
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, 53215
Medical College of Wisconsin, Department of Neurology
Milwaukee, Wisconsin, 53226
Aurora Sinai Medical Center-Arrhythmia Center
Milwaukee, Wisconsin, 53233
Parkinson's Institute and Clinical Center
Mountain View, California, 94040
Vanderbilt University Autonomic Dysfunction Center - Clinical Trials Center
Nashville, Tennessee, 37232
Yale-New Haven Hospital
New Haven, Connecticut, 06510
Yale Neurology / Hypertension Program
New Haven, Connecticut, 06519
Yale University School Of Medicine
New Haven, Connecticut, 06520
Parker Jewish Institute for Health Care & Rehabilitation
New Hyde Park, New York, 11040
Weill Cornell Medical College, Dept. of Neurology
New York, New York, 10021
The Bendheim Parkinson and Movement Disorders Center
New York, New York, 10029
Columbia University Medical Center
New York, New York, 10032
Project 4 Research, Inc., The Neurological Institute at Columbia University Medical Center
New York, New York, 10032
The Neurological Institute at Columbia University Medical Center
New York, New York, 10032
Parker Jewish Institute For Healthcare And Rehabilitation
New York, New York, 11542
Christiana Care Neurology Specialists
Newark, Delaware, 19713
Health Research of Hampton Roads-Norfolk, Inc
Norfolk, Virginia, 23502
Sentara Neurology Specialists
Norfolk, Virginia, 23507
COR Clinical Research, LLC
Oklahoma City, Oklahoma, 73103
Methodist Physicians Clinic - Heart Consultants
Omaha, Nebraska, 68114
MPC Heart Consultants
Omaha, Nebraska, 68114
University Of Nebraska Medical Center
Omaha, Nebraska, 68198-8435
The Nebraska Medical Center
Omaha, Nebraska, 68198
Diverse Research Solutions, LLC
Oxnard, California, 93030
Focilmed
Oxnard, California, 93030
Parkinsons Disease & Movement Disorder of Silicon Valley
Palo Alto, California, 94301
Neurosearch, Inc. - Pasedena
Pasadena, California, 91105
Neurosearch, Inc. - Ventura
Pasadena, California, 91105
SC3 Research Group
Pasadena, California, 91105
Drexel Neurosciences Institute
Philadelphia, Pennsylvania, 19102
University of Pennsylvania, Parkinson's Disease & Movement Disorders Center
Philadelphia, Pennsylvania, 19107
21st Century Neurology
Phoenix, Arizona, 85004
University of Pittsburgh, Department of Neurology
Pittsburgh, Pennsylvania, 15213
Island Neurological Associates
Plainview, New York, 11803
Neurostudies, Inc.
Port Charlotte, Florida, 33952
Parkinson's Disease Treatment Center of Southwest Florida
Port Charlotte, Florida, 33952
Legacy / Oregon Clinic Neurology
Portland, Oregon, 97210
The Oregon Clinic
Portland, Oregon, 97210
Sunbeam Clinical Research, LLC.
Prosper, Texas, 75078
Dr. Umer Akbar MD, Office of
Providence, Rhode Island, 02903
Rhode Island Hospital
Providence, Rhode Island, 02905
Neurosearch, Inc. - Reseda
Reseda, California, 91335
Henrico Doctors Neurology Associates, LLC
Richmond, Virginia, 23226
Carilion Clinic
Roanoke, Virginia, 24016
Central Texas Neurology Consultants
Round Rock, Texas, 78681
Radiological Associates of Sacramento
Sacramento, California, 95815
Sutter Neuroscience
Sacramento, California, 95816
Bateman Home Center
Salt Lake City, Utah, 84102
Maine Medical Partners Technology
Scarborough, Maine, 04074
Movement Disorders Center of Arizona
Scottsdale, Arizona, 85258
Northwest Neurology, Premier Clinical Research
Spokane, Washington, 99202
Premeir Clinical Research
Spokane, Washington, 99202
Alpha Neurology
Staten Island, New York, 10306
The Parkinson's Institute and Clinical Center
Sunnyvale, California, 94085
Eminance Medical & Clinical Research
Tampa, Florida, 33604
University Of South Florida
Tampa, Florida, 33613
USF Parkinson's & Movement Disorders Center
Tampa, Florida, 33613
Gardner-McMaster Parkinson Center - The University of Toledo
Toledo, Ohio, 43614
Medical College of Ohio, Department of Neurology
Toledo, Ohio, 43614
Neuroscience Research Institute, LLC
Toms River, New Jersey, 08755
Neurosearch Inc. - Torrance
Torrance, California, 90505
Northern Michigan Neurology
Traverse City, Michigan, 49684
Nothern Michigan Neurology
Traverse City, Michigan, 49684
Center For Neurosciences
Tucson, Arizona, 85718
Movement Disorder Clinic - The University of Arizona
Tucson, Arizona, 85724-5023
University of Arizona Health Sciences Center, Department Of Neurology
Tucson, Arizona, 85724
Christus Research Institute
Tyler, Texas, 75701
Vero Neurology
Vero Beach, Florida, 32960
Geodyssey Research, LLC
Vero Beach, Florida, 32962
Georgetown University
Washington D.C., District of Columbia, 20007
MedStar Georgetown-MedStar Georgetown Transplant Institute University Hospital (MGUH)
Washington D.C., District of Columbia, 20007
Clear Lake Specialties
Webster, Texas, 77598
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322
Helen Hayes Hospital
West Haverstraw, New York, 10093
UBMD Neurology
Williamsville, New York, 14221
Central Dupage Hospital
Winfield, Illinois, 60190
Northwestern Medicine Central DuPage Hospital
Winfield, Illinois, 60190
About this study
Official title: RESTORE: A Clinical Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension to Assess Sustained Effects of Droxidopa Therapy
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)
Read the 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
- Being tested
- Droxidopa capsules, Placebo capsules
- Keywords
- Parkinson's Disease, Multiple System Atrophy, Pure Autonomic Failure, Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency
- Medical subject headings
- Parkinson Disease, Multiple System Atrophy, Pure Autonomic Failure, dopamine beta hydroxylase deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Droxidopa capsulesDrug
Also called Northera
100, 200 or 300 mg
Placebo capsulesDrug
Also called Placebo
| Study group | Role | What they receive |
|---|---|---|
| Open Label Period | Experimental | 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). Receives: Drug: Droxidopa capsules |
| Randomized Period | Placebo comparator | 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. Receives: Drug: Droxidopa capsules; Drug: Placebo capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time To Intervention
Kaplan-Meier estimates are presented for time to treatment intervention. The estimates represent the quartiles of the survival time, where 50% corresponds to the median time to need for treatment intervention.
Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Treatment Period:
- OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) AND lack of efficacy as judged by the investigator; OR
- OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at 2 consecutive visits; OR
- OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at the visit before early discontinuation; OR
- participant stops IMP or withdraws from study for patient-reported lack of efficacy.
Measured: Randomization (Day 0) up to Week 12
Secondary outcomes (6)
Number of Participants Who Needed Intervention During the 12-week Double-Blind Treatment Period
Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Treatment Period:
- OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) AND lack of efficacy as judged by the investigator; OR
- OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at 2 consecutive visits; OR
- OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at the visit before early discontinuation; OR
- participant stops IMP or withdraws from study for patient-reported lack of efficacy.
Measured: Randomization (Day 0) up to Week 12
Time To All-cause Discontinuation
Kaplan-Meier estimates are presented for time to all-cause discontinuation. The estimates represent the quartiles of the survival time, where 50% corresponds to the median time to discontinuation. Time to all-cause discontinuation was defined as the time from randomization to withdrawal or last contact date.
Measured: Randomization (Day 0) up to Week 12
Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score
The OHSA scale was designed to rate symptoms occurring specifically as a result of low blood pressure (BP), on average, over the past week using an 11-point scale (0 to 10), with more severe symptoms scoring higher. A score of zero indicates that the symptom was not experienced, and 10 is the worst possible. The scale was used to assess six symptoms: 1) Dizziness, lightheadedness, feeling faint, or feeling like you might black out, 2) problems with vision, 3) weakness, 4) fatigue, 5) trouble concentrating, and 6) head/neck discomfort. Scores for each activity and a composite score for all six activities were tabulated. A mean negative change from baseline means that symptoms have improved. A mean positive change from baseline means that symptoms have gotten worse.
Measured: Randomization (Day 0); Weeks 2 to 12
Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score
The OHQ composite score was a mean of the OHSA composite and the Orthostatic Hypotension Daily Activity Scale (OHDAS) composite scores. The OHDAS was designed as a measure of quality of life. It uses an 11-point scale to assess whether orthostatic hypotension (OH) "interfered" with four types of activities: 1) standing for a short time, 2) standing for a long time, 3) walking for a short time, and 4) walking for a long time. A zero rating means that over the preceding week the activity was performed with no interference and a 10 rating means that orthostatic hypotension completely interfered with the activity. Scores for each activity and a composite score for all four activities were tabulated. A mean negative change from baseline means that symptoms have improved. A mean positive change from baseline means that symptoms have gotten worse.
Measured: Randomization (Day 0); Weeks 2 to 12
Clinician-rated Clinical Global Impressions - Severity (CGI-S)
The CGI-S was developed to provide global measures of the severity of a participant's clinical condition during clinical studies. The CGI-S was utilized by both the clinician and the participant to provide an impression of the participant's current state of OH. The severity of the participant's current illness was rated by the clinician on a 7-point scale ranging from 1 (normal, no OH) to 7 (among those patients most extremely ill with OH).
Measured: Weeks 2 to 12
Participant-rated CGI-S
The CGI-S was developed to provide global measures of the severity of a participant's clinical condition during clinical studies. The CGI-S was utilized by both the clinician and the participant to provide an impression of the participant's current state of OH. The severity of the participant's current illness was rated by the participant on a 7-point scale ranging from 1 (normal, no OH) to 7 (most extremely ill with OH).
Measured: Weeks 2 to 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2015 (estimated)
- Study start11 Feb 2016
- Primary completion21 Jul 2022
- Study completion9 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Symptomatic Neurogenic Orthostatic HypotensionStudies of the same condition, open and under way.
- More trials run by H. Lundbeck A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 453 participants (actual)
Sponsor and investigators
- Lead sponsor
- H. Lundbeck A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Email contact via H. Lundbeck A/S, Study director, LundbeckClinicalTrials@Lundbeck.com
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02586623
- Sponsor's protocol ID
- 16306A
- Other IDs
- NOH402
- Acronym
- RESTORE
- Status last verified
- Aug 2023
- First submitted
- 23 Oct 2015
- Last updated
- 23 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 35107750
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RESTORE: A Clinical Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension to Assess Sustained Effects of Droxidopa Therapy
- ClinicalTrials.gov ID
- NCT02586623
- Acronym / sponsor ID
- RESTORE / 16306A
- Keywords
- Parkinson's Disease, Multiple System Atrophy, Pure Autonomic Failure, Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 453 participants (actual)
- Lead sponsor
- H. Lundbeck A/SIndustry (pharma, biotech, devices)
- Study start
- 11 Feb 2016 (actual)
- Primary completion
- 21 Jul 2022 (actual)
- Study completion
- 9 Sep 2022 (actual)
- First posted
- 26 Oct 2015 (estimated)
- Results
- Posted 23 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Open Label Period | Experimental | Drug: Droxidopa capsulesActive 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). |
| Randomized Period | Placebo comparator | Drug: Droxidopa capsules, Drug: Placebo capsulesActive 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Droxidopa capsulesAlso: Northera100, 200 or 300 mg | Drug | Open Label Period, Randomized Period |
| Placebo capsulesAlso: Placebo | Drug | Randomized Period |
Primary outcome
Time To Intervention
Time frame: Randomization (Day 0) up to Week 12
Kaplan-Meier estimates are presented for time to treatment intervention. The estimates represent the quartiles of the survival time, where 50% corresponds to the median time to need for treatment intervention. Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Treatment Period: * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) AND lack of efficacy as judged by the investigator; OR * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at 2 consecutive visits; OR * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at the visit before early discontinuation; OR * participant stops IMP or withdraws from study for patient-reported lack of efficacy.
6 secondary outcomes
Number of Participants Who Needed Intervention During the 12-week Double-Blind Treatment Period
Time frame: Randomization (Day 0) up to Week 12
Time To All-cause Discontinuation
Time frame: Randomization (Day 0) up to Week 12
Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score
Time frame: Randomization (Day 0); Weeks 2 to 12
Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score
Time frame: Randomization (Day 0); Weeks 2 to 12
Clinician-rated Clinical Global Impressions - Severity (CGI-S)
Time frame: Weeks 2 to 12
Participant-rated CGI-S
Time frame: Weeks 2 to 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35107750Hauser 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Email contact via H. Lundbeck A/S study director
LundbeckClinicalTrials@Lundbeck.com
168 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Droxidopa capsules in people with Symptomatic Neurogenic Orthostatic Hypotension, run by H. Lundbeck A/S at 168 sites in United States.
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 16 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: finished, as of the sponsor's last update on 23 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 168 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 23 Aug 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?
Time To Intervention (time frame: Randomization (Day 0) up to Week 12). 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 NCT02586623, 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 23 Aug 2023.