Neurogenic Orthostatic HypotensionPhase 3NOH303NCT00738062
Open-Label Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)
A Phase 3 study testing Droxidopa in people with Neurogenic Orthostatic Hypotension and Non-Diabetic Autonomic Neuropathy, run by Chelsea Therapeutics at 54 sites in 4 countries.
Trial summary
The purpose of this study is to assess the durability of effect of Droxidopa in treating symptoms of neurogenic orthostatic hypotension in patients with Primary Autonomic Failure (Pure Autonomic Failure, Multiple System Atrophy, Parkinson's Disease), Non-diabetic neuropathy, or Beta Hydroxylase deficiency. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurogenic Orthostatic Hypotension, Non-Diabetic Autonomic Neuropathy, Multiple System Atrophy
- What is being tested?
- Droxidopa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 54 sitesin 4 countries
- Study dates
- Jan 2008to Dec 2010
- Phase
- Phase 3
- 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
- To be eligible for inclusion, each patient must fulfill the following criteria:
- Participated in Droxidopa Protocol 302;
- 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.
Who cannot join
- Patients are not eligible for this study if they fulfill one or more of the following criteria:
- Currently taking ephedrine or midodrine;
- Patients taking ephedrine or midodrine must stop taking these drugs at least 2 days prior to their study entry visit (Visit 1).
- Currently taking anti-hypertensive medication;
- The use of short-acting anti-hypertensive medications at bedtime is permitted.
- Currently taking tri-cyclic antidepressant medication or other norepinephrine re-uptake inhibitors;
Show all 32Show fewer
- Have changed dose, frequency and or type of prescribed medication, within two weeks of study start (excluding ephedrine and midodrine);
- History of more than moderate alcohol consumption;
- History of known or suspected drug or substance abuse;
- Women of childbearing potential who are not using a medically accepted contraception;
- Reproductive potential:
- Female subjects should be either post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile, or women of child-bearing potential (WOCP) who are using or agree to use acceptable methods of contraception.
- Acceptable contraceptives include intrauterine devices (IUDs), hormonal contraceptives (oral, depot, patch or injectable) and double barrier methods such as condoms or diaphragms with spermicidal gel or foam.
- For WOCP a urine pregnancy test must be conducted at each study visit.
- WOCP must be advised to use acceptable contraceptives throughout the study period and for 30 days after the last dose of investigational product.
- If hormonal contraceptives are used they should be taken according to the package insert.
- WOCP who are not currently sexually active must agree to use acceptable contraception, as defined above, if they decide to become sexually active during the period of the study and for 30 days after the last dose of investigational product.
- Sexually active males whose partner is a WOCP and who do not agree to use condoms for the duration of the study and for 30 days after the last dose;
- Women who are pregnant or breast feeding;
- Known or suspected hypersensitivity to the study medication or any of its ingredients;
- Pre-existing sustained severe hypertension (BP 180/110 mmHg in the sitting position);
- Have atrial fibrillation or, in the investigator's opinion, have any other significant cardiac arrhythmia;
- Any other significant systemic, hepatic, cardiac or renal illness;
- Diabetes mellitus or insipidus;
- Have a history of closed angle glaucoma;
- Have a known or suspected malignancy;
- Have a serum creatinine level > 130 umol/L;
- Patients with known gastrointestinal illness or other gastrointestinal disorder that may, in the investigator's opinion, affect the absorption of study drug;
- In the investigator's opinion, have clinically significant abnormalities on clinical examination or laboratory testing;
- In the investigator's opinion, are unable to adequately co-operate because of individual or family situation;
- In the investigator's opinion, are suffering from a mental disorder that interferes with the diagnosis and/or with the conduct of the study, e.g. schizophrenia, major depression, dementia;
- Are not able or willing to comply with the study requirements for the duration of the study.
Trial locations and contacts
54 sites in 4 countries.
54 sites in 4 countries
United States44 sites
University of Maryland Hospital
Baltimore, Maryland, 21201
Jacinto Medical Group, PA
Baytown, Texas, 77521
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Parkinson's Disease & Movment Disorder Center
Boca Raton, Florida, 33486
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Medical Associates of North Georgia
Canton, Georgia, 30114
Saint Mary of Nazareth Hospital Center
Chicago, Illinois, 60622
University of Cincinnati
Cincinnati, Ohio, 45267
University Hospitals Case Medical Center
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
Electrophysiology Associates
Colorado Springs, Colorado, 80910
UT Southwestern Medical Center
Dallas, Texas, 75390-9036
Duke University Medical Center
Durham, North Carolina, 27705
New Jersey Neuroscience Institute
Edison, New Jersey, 08818
Indiana Medical Research
Elkhart, Indiana, 46514
The Parkinson's and Movement Disorders Institute
Fountain Valley, California, 92708
Southeastern Integrated Medical
Gainesville, Florida, 32607
JWM Neurology
Indianapolis, Indiana, 46237
Mayo Jacksonville Florida Department of Neurology
Jacksonville, Florida, 32224
Kingston Neurological Associates, PC
Kingston, New York, 12401
Dedicated Clinical Research
Litchfield Park, Arizona, 85340
University of Louisville
Louisville, Kentucky, 40202
University of Miami Miller School of Medicine
Miami, Florida, 33136
Vanderbilt University
Nashville, Tennessee, 37212
NYU Medical Center
New York, New York, 10016
Columbia University Neurological institute of NY
New York, New York, 10032
North Chicago VA Medical Center
North Chicago, Illinois, 60064
COR Clinical Research, LLC
Oklahoma City, Oklahoma, 73103
Kansas City Bone and Joint, PA
Overland Park, Kansas, 66211
Pacific Neuroscience Medical Group
Oxnard, California, 93030
Xenoscience Inc.
Phoenix, Arizona, 85004
The Oregon Clinic
Portland, Oregon, 97213
Mayo Clinic Rochester
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14618
Scott & White Healthcare - Round Rock
Round Rock, Texas, 78665
Henry Ford Health System
Southfield, Michigan, 48034
Washington University Medical Center
St Louis, Missouri, 63110
Sun Health Research Institute
Sun City, Arizona, 85351
The Parkinson's Institute
Sunnyvale, California, 94085
University of South Florida
Tampa, Florida, 33606
Scott & White Memorial Hospital & Clinic
Temple, Texas, 76508
East Texas Medical Center - Neurological Institute Movment Disorders Center
Tyler, Texas, 75701
Wake Forest University
Winston-Salem, North Carolina, 27157
University of Massachusetts Worcester
Worcester, Massachusetts, 01655
Canada5 sites
McMaster University
Hamilton, Ontario, L8L2X2
Centre for Movement Disorders
Markham, Ontario, L6B1C9
SMBD Jewish General Hospital - Department of Neurology
Montreal, Quebec, H3T 1E2
Parkinson's & Neurodegenerative Disorders Clinic
Ottawa, Ontario, K1G4G3
Quebec Memory and Motor Skills Disorders Clinic
Québec, Quebec, G1R 3X5
Australia3 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Austin Hospital
Heidelburg, 3084
Baker Heart Research Institute
Melbourne, Victoria, 3004
New Zealand2 sites
Van der Veer Institute for Parkinson's Disease and Movement Disorders
Christchurch
Auckland Hospital
Grafton Auckland, Private Bag
About this study
Official title: An Open-label Study, to Assess the Long-term Safety and Clinical Benefit of Droxidopa in Subjects With PAF, Dopamine Beta Hydroxylase Deficiency or Non-diabetic Neuropathy and Symptomatic Neurogenic Orthostatic Hypotension
The purpose of this study is to assess the durability of effect of Droxidopa in treating symptoms of neurogenic orthostatic hypotension in patients with Primary Autonomic Failure (Pure Autonomic Failure, Multiple System Atrophy, Parkinson's Disease), Non-diabetic neuropathy, or Beta Hydroxylase deficiency.
Read the detailed description
Systolic blood pressure is transiently and minimally decreased in healthy individuals upon standing. Normal physiologic feedback mechanisms work through neurally-mediated pathways to maintain the standing blood pressure, and thus maintain adequate cerebral perfusion. The compensatory mechanisms that regulate blood pressure upon standing are dysfunctional in subjects with orthostatic hypotension (OH), a condition that may lead to inadequate cerebral perfusion with accompanying symptoms of syncope, dizziness or lightheadedness, unsteadiness and blurred or impaired vision, among other symptoms.
The autonomic nervous system has a central role in the regulation of blood pressure. Primary Autonomic Failure is manifested in a variety of syndromes. Orthostatic hypotension is a usual presenting symptom. Primary Autonomic Failure may be the primary diagnosis, and classifications include pure autonomic failure (PAF), also called idiopathic orthostatic hypotension (Bradbury-Eggleston syndrome) autonomic failure with multiple system atrophy (Shy-Drager syndrome) and also Parkinson's disease. Regardless of the primary condition, autonomic dysfunction underlies orthostatic hypotension.
Orthostatic hypotension may be a severely disabling condition which can seriously interfere with the quality of life of afflicted subjects. Currently available therapeutic options provide some symptomatic relief in a subset of subjects, but are relatively ineffective and are often accompanied by severe side effects that limit their usefulness. Support garments (tight-fitting leotard) may prove useful in some subjects, but is difficult to don without family or nursing assistance, especially for older subjects. Midodrine, fludrocortisone, methylphenidate, ephedrine, indomethacin and dihydroergotamine are among some of the pharmacological interventions that have been used to treat orthostatic hypotension, although only midodrine is specifically approved for this indication. The limitations of these currently available therapeutic options, and the incapacitating nature and often progressive downhill course of disease, point to the need for an improved therapeutic alternative.
The current withdrawal design study will measure the efficacy of droxidopa on symptoms of neurogenic orthostatic hypotension in patients randomized to continued droxidopa treatment versus placebo, following 14 days of double-blind treatment.
Droxidopa
Droxidopa [also, known as L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS, or L-DOPS] is the International non-proprietary name (INN) for a synthetic amino acid precursor of norepinephrine (NE), which was originally developed by Sumitomo Pharmaceuticals Co., Limited, Japan. It has been approved for use in Japan since 1989. Droxidopa has been shown to improve symptoms of orthostatic hypotension that result from a variety of conditions including Shy Drager syndrome (Multiple System Atrophy), Pure Autonomic Failure, and Parkinson's disease. There are four stereoisomers of DOPS; however, only the L-threo-enantiomer (droxidopa) is biologically active.
The exact mechanism of action of droxidopa in the treatment of symptomatic NOH has not been precisely defined; however, its NE replenishing properties with concomitant recovery of decreased noradrenergic activity are considered to be of major importance.
Droxidopa has been marketed in Japan since 1989. Data from clinical studies and post-marketing surveillance programs conducted in Japan show that the most commonly reported adverse drug reactions with droxidopa are increased blood pressure, nausea, and headache. In clinical studies, the prevalence and severity of droxidopa adverse effects appear to be similar to those reported by the placebo control arm.
- Conditions
- Neurogenic Orthostatic Hypotension, Non-Diabetic Autonomic Neuropathy, Multiple System Atrophy, Dopamine Beta Hydroxylase Deficiency
- Being tested
- Droxidopa, Placebo
- Keywords
- NOH, Neurogenic Orthostatic Hypotension, Orthostatic hypotension, PAF, Pure Autonomic Failure, MSA, Multiple System Atrophy, Neuropathy, Autonomic Failure, Parkinson, Dopamine Deficiency, Dopamine, Droxidopa
- Medical subject headings
- Multiple System Atrophy, dopamine beta hydroxylase deficiency, Hypotension, Orthostatic, Pure Autonomic Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DroxidopaDrug
100 mg, oral, three times per day 200 mg, oral, three times per day 300 mg, oral, three times per day 400 mg, oral, three times per day 500 mg, oral, three times per day 600 mg, oral, three times per day
PlaceboDrug
Also called Inactive drug (to look like Droxidopa)
100 mg, oral, three times per day 200 mg, oral, three times per day 300 mg, oral, three times per day 400 mg, oral, three times per day 500 mg, oral, three times per day 600 mg, oral, three times per day
| Study group | Role | What they receive |
|---|---|---|
| Droxidopa | Active comparator | Study medication Receives: Drug: Droxidopa |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Orthostatic Hypotension Questionnaire Composite Score (OHQ)
The OHQ is the average of two sub-scales, the Orthostatic Hypotension Symptom Assessment Scale (OHSA) and the Orthostatic Hypotension Daily Activities Scale (OHDAS). Each asks the patient to rate their symptoms or disease impact over the past week. The OHSA sub-scale is the average of six items: 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. The OHDAS sub-scale is the average of four items: 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. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe.
In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug). All patients are on open-label droxidopa for 3 months prior to randomization.
Measured: 14 days
Secondary outcomes (7)
Change in Orthostatic Hypotension Daily Activities (OHDAS) Score
The OHDAS scale is the average of four items: 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. Each asks the patient to rate their disease impact over the past week. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe.
Change: score at end of randomization minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug).
Measured: 14 days
Change in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score
The OHSA scale is the average of six items: 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. Each asks the patient to rate their symptoms over the past week. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe.
Change: score at end of randomization minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug).
Measured: 14 days
Change in Systolic Blood Pressure (SBP) Measurements 3 Minutes Post Standing
Change: standing systolic blood pressure at end of study minus standing systolic blood pressure at randomization. In this withdrawal design, a negative score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug). All patients are on open-label droxidopa for 3 months prior to randomization to either continued droxidopa or to placebo.
Measured: 14 days
Patient Reported Clinical Global Impression - Severity
The CGI-S is a 7 point scale ranging from a score of 1 (no symptoms) to 7 (severe symptoms). Patients were grouped according to OH severity at the end of the randomization period as follows;
- Normal-Borderline OH (CGI-S 1-2),
- Mild-Moderate OH (CGI-S 3-4),
- Marked OH-Most Ill with OH (CGI-S 5-7). .
Measured: 14 days
Clinician Recorded Clinical Global Impression - Severity
The CGI-S is a 7 point scale ranging from a score of 1 (no symptoms) to 7 (severe symptoms). Patients were grouped according to OH severity at the end of the randomization period as follows;
- Normal-Borderline OH (CGI-S 1-2),
- Mild-Moderate OH (CGI-S 3-4),
- Marked OH-Most Ill with OH (CGI-S 5-7).
Measured: 14 days
Patient Reported Clinical Global Impression - Improvement
The CGI-I is a 7 point scale ranging from a score of 1 (very much improved) to 7 (very much worse), with no change in the middle, and assesses the improvement in relation to the baseline evaluation.
Patients will be grouped according change in disease as follows;
- Very Much Improved to Slightly Improved (CGI-I 1-3),
- No Change (CGI-I 4),
- Slightly Worse to Very Much Worse (CGI-I 5-7).
Measured: 14 days
Clinician Rated Clinical Global Impressions - Improvement
The CGI-I is a 7 point scale ranging from a score of 1 (very much improved) to 7 (very much worse), with no change in the middle, and assesses the improvement in relation to the baseline evaluation.
Patients will be grouped according change in disease as follows;
- Very Much Improved to Slightly Improved (CGI-I 1-3),
- No Change (CGI-I 4),
- Slightly Worse to Very Much Worse (CGI-I 5-7).
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2008 (estimated)
- Study startJan 2008
- Primary completionDec 2010
- Study completionDec 2010
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.
- Other trials for Neurogenic Orthostatic HypotensionStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chelsea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Horacio Kaufmann Kaufmann, MD, Principal investigator, NYU School of MedicineChristopher J. Mathias, MD, Principal investigator, Imperial School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00738062
- Sponsor's protocol ID
- Droxidopa NOH303
- Acronym
- NOH303
- Status last verified
- Apr 2014
- First submitted
- 19 Aug 2008
- Last updated
- 16 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study, to Assess the Long-term Safety and Clinical Benefit of Droxidopa in Subjects With PAF, Dopamine Beta Hydroxylase Deficiency or Non-diabetic Neuropathy and Symptomatic Neurogenic Orthostatic Hypotension
- ClinicalTrials.gov ID
- NCT00738062
- Acronym / sponsor ID
- NOH303 / Droxidopa NOH303
- Conditions
- Neurogenic Orthostatic Hypotension, Non-Diabetic Autonomic Neuropathy, Multiple System Atrophy, Dopamine Beta Hydroxylase Deficiency
- Keywords
- NOH, Neurogenic Orthostatic Hypotension, Orthostatic hypotension, PAF, Pure Autonomic Failure, MSA, Multiple System Atrophy, Neuropathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Chelsea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jan 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 20 Aug 2008 (estimated)
- Results
- Posted 16 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the durability of effect of Droxidopa in treating symptoms of neurogenic orthostatic hypotension in patients with Primary Autonomic Failure (Pure Autonomic Failure, Multiple System Atrophy, Parkinson's Disease), Non-diabetic neuropathy, or Beta Hydroxylase deficiency.
Detailed description
Systolic blood pressure is transiently and minimally decreased in healthy individuals upon standing. Normal physiologic feedback mechanisms work through neurally-mediated pathways to maintain the standing blood pressure, and thus maintain adequate cerebral perfusion. The compensatory mechanisms that regulate blood pressure upon standing are dysfunctional in subjects with orthostatic hypotension (OH), a condition that may lead to inadequate cerebral perfusion with accompanying symptoms of syncope, dizziness or lightheadedness, unsteadiness and blurred or impaired vision, among other symptoms.
The autonomic nervous system has a central role in the regulation of blood pressure. Primary Autonomic Failure is manifested in a variety of syndromes. Orthostatic hypotension is a usual presenting symptom. Primary Autonomic Failure may be the primary diagnosis, and classifications include pure autonomic failure (PAF), also called idiopathic orthostatic hypotension (Bradbury-Eggleston syndrome) autonomic failure with multiple system atrophy (Shy-Drager syndrome) and also Parkinson's disease. Regardless of the primary condition, autonomic dysfunction underlies orthostatic hypotension.
Orthostatic hypotension may be a severely disabling condition which can seriously interfere with the quality of life of afflicted subjects. Currently available therapeutic options provide some symptomatic relief in a subset of subjects, but are relatively ineffective and are often accompanied by severe side effects that limit their usefulness. Support garments (tight-fitting leotard) may prove useful in some subjects, but is difficult to don without family or nursing assistance, especially for older subjects. Midodrine, fludrocortisone, methylphenidate, ephedrine, indomethacin and dihydroergotamine are among some of the pharmacological interventions that have been used to treat orthostatic hypotension, although only midodrine is specifically approved for this indication. The limitations of these currently available therapeutic options, and the incapacitating nature and often progressive downhill course of disease, point to the need for an improved therapeutic alternative.
The current withdrawal design study will measure the efficacy of droxidopa on symptoms of neurogenic orthostatic hypotension in patients randomized to continued droxidopa treatment versus placebo, following 14 days of double-blind treatment.
Droxidopa
Droxidopa [also, known as L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS, or L-DOPS] is the International non-proprietary name (INN) for a synthetic amino acid precursor of norepinephrine (NE), which was originally developed by Sumitomo Pharmaceuticals Co., Limited, Japan. It has been approved for use in Japan since 1989. Droxidopa has been shown to improve symptoms of orthostatic hypotension that result from a variety of conditions including Shy Drager syndrome (Multiple System Atrophy), Pure Autonomic Failure, and Parkinson's disease. There are four stereoisomers of DOPS; however, only the L-threo-enantiomer (droxidopa) is biologically active.
The exact mechanism of action of droxidopa in the treatment of symptomatic NOH has not been precisely defined; however, its NE replenishing properties with concomitant recovery of decreased noradrenergic activity are considered to be of major importance.
Droxidopa has been marketed in Japan since 1989. Data from clinical studies and post-marketing surveillance programs conducted in Japan show that the most commonly reported adverse drug reactions with droxidopa are increased blood pressure, nausea, and headache. In clinical studies, the prevalence and severity of droxidopa adverse effects appear to be similar to those reported by the placebo control arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Droxidopa | Active comparator | Drug: DroxidopaStudy medication |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Participated in Droxidopa Protocol 302;
- 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 (32 listed)
- Patients are not eligible for this study if they fulfill one or more of the following criteria:
- Currently taking ephedrine or midodrine;
- Patients taking ephedrine or midodrine must stop taking these drugs at least 2 days prior to their study entry visit (Visit 1).
- Currently taking anti-hypertensive medication;
- Currently taking tri-cyclic antidepressant medication or other norepinephrine re-uptake inhibitors;
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 |
|---|---|---|
| Droxidopa100 mg, oral, three times per day 200 mg, oral, three times per day 300 mg, oral, three times per day 400 mg, oral, three times per day 500 mg, oral, three times per day 600 mg, oral, three times per day | Drug | Droxidopa |
| PlaceboAlso: Inactive drug (to look like Droxidopa)100 mg, oral, three times per day 200 mg, oral, three times per day 300 mg, oral, three times per day 400 mg, oral, three times per day 500 mg, oral, three times per day 600 mg, oral, three times per day | Drug | Placebo |
Primary outcome
Change in Orthostatic Hypotension Questionnaire Composite Score (OHQ)
Time frame: 14 days
The OHQ is the average of two sub-scales, the Orthostatic Hypotension Symptom Assessment Scale (OHSA) and the Orthostatic Hypotension Daily Activities Scale (OHDAS). Each asks the patient to rate their symptoms or disease impact over the past week. The OHSA sub-scale is the average of six items: 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. The OHDAS sub-scale is the average of four items: 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. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug). All patients are on open-label droxidopa for 3 months prior to randomization.
7 secondary outcomes
Change in Orthostatic Hypotension Daily Activities (OHDAS) Score
Time frame: 14 days
Change in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score
Time frame: 14 days
Change in Systolic Blood Pressure (SBP) Measurements 3 Minutes Post Standing
Time frame: 14 days
Patient Reported Clinical Global Impression - Severity
Time frame: 14 days
Clinician Recorded Clinical Global Impression - Severity
Time frame: 14 days
Patient Reported Clinical Global Impression - Improvement
Time frame: 14 days
Clinician Rated Clinical Global Impressions - Improvement
Time frame: 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Horacio Kaufmann Kaufmann, MD principal investigator
NYU School of Medicine
Christopher J. Mathias, MD principal investigator
Imperial School of Medicine
54 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Droxidopa in people with Neurogenic Orthostatic Hypotension and Non-Diabetic Autonomic Neuropathy, run by Chelsea Therapeutics at 54 sites in 4 countries.
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 3 inclusion and 32 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 16 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 54 sites in United States, Canada, Australia, New Zealand. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 16 May 2014). 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?
Change in Orthostatic Hypotension Questionnaire Composite Score (OHQ) (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 May 2014.