|
|
|
|
|
|
Sponsored by: |
Chelsea Therapeutics |
Information provided by: | Chelsea Therapeutics |
ClinicalTrials.gov Identifier: | NCT00738062 |
The purpose of this study is to see whether 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.
Condition | Intervention | Phase |
Symptomatic Neurogenic Orthostatic Hypotension (NOH) Non-Diabetic Neuropathy Primary Autonomic Failure Dopamine Beta Hydroxylase Deficiency |
Drug: Droxidopa Drug: Placebo |
Phase III |
Genetics Home Reference related topics: | dopamine beta-hydroxylase deficiency |
MedlinePlus related topics: | Low Blood Pressure Parkinson's Disease |
ChemIDplus related topics: | Dopamine Dopamine hydrochloride Droxidopa |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy 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 |
Estimated Enrollment: | 118 |
Study Start Date: | January 2008 |
Estimated Study Completion Date: | February 2010 |
Estimated Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
Droxidopa: Active Comparator
Study medication
|
Drug: 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
|
Placebo: Placebo Comparator |
Drug: Placebo
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
|
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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
To be eligible for inclusion, each patient must fulfill the following criteria:
Exclusion Criteria:
Patients are not eligible for this study if they fulfill one or more of the following criteria:
Currently taking anti-hypertensive medication;
* The use of short-acting anti-hypertensive medications at bedtime is permitted.
Women of childbearing potential who are not using a medically accepted contraception;
United States, Arizona | |||||
Dedicated Clinical Research | |||||
Litchfield Park, Arizona, United States, 85340 | |||||
Sun Health Research Institute | |||||
Sun City, Arizona, United States, 85351 | |||||
United States, California | |||||
Pacific Neuroscience Medical Group, Inc | |||||
Oxnard, California, United States, 93030 | |||||
Pacific Neuroscience Medical Group | |||||
Oxnard, California, United States, 93030 | |||||
The Parkinson's Institute | |||||
Sunnyvale, California, United States, 94085 | |||||
United States, Florida | |||||
Southeastern Integrated Medical | |||||
Gainesville, Florida, United States, 32607 | |||||
United States, Indiana | |||||
Indiana Medical Research | |||||
Elkhart, Indiana, United States, 46514 | |||||
United States, Kansas | |||||
Kansas City Bone and Joint, PA | |||||
Overland Park, Kansas, United States, 66211 | |||||
United States, Massachusetts | |||||
Beth Israel Deaconess Medical Center | |||||
Boston, Massachusetts, United States, 02215 | |||||
University of Massachusetts Worcester | |||||
Worcester, Massachusetts, United States, 01655 | |||||
United States, Michigan | |||||
Henry Ford Health System | |||||
Southfield, Michigan, United States, 48034 | |||||
United States, Minnesota | |||||
Mayo Clinic Rochester | |||||
Rochester, Minnesota, United States, 55905 | |||||
United States, New Jersey | |||||
JFK Medical Center | |||||
Edison, New Jersey, United States, 08818 | |||||
United States, New York | |||||
NYU Medical Center | |||||
New York City, New York, United States, 10016 | |||||
University of Rochester | |||||
Rochester, New York, United States, 14618 | |||||
United States, Ohio | |||||
Cleveland Clinic | |||||
Cleveland, Ohio, United States, 44195 | |||||
United States, Oklahoma | |||||
COR Clinical Research, LLC | |||||
Oklahoma City, Oklahoma, United States, 73103 | |||||
COR Clinical Research | |||||
Oklahoma City, Oklahoma, United States, 73103 | |||||
United States, Texas | |||||
UT Southwestern Medical Center | |||||
Dallas, Texas, United States, 75390-9036 |
Chelsea Therapeutics |
Responsible Party: | Chelsea Therapeutics ( Cameron Szakacs ) |
Study ID Numbers: | Droxidopa 303 |
First Received: | August 19, 2008 |
Last Updated: | August 19, 2008 |
ClinicalTrials.gov Identifier: | NCT00738062 |
Health Authority: | United States: Food and Drug Administration |
|
|
|
|
|
|