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Sponsors and Collaborators: |
Chelsea Therapeutics Chiltern International Inc. |
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Information provided by: | Chelsea Therapeutics |
ClinicalTrials.gov Identifier: | NCT00633880 |
The purpose of this study is to see whether droxidopa is effective 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 |
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Symptomatic Neurogenic Orthostatic Hypotension (NOH) Non-diabetic Neuropathy Primary Autonomic Failure Dopamine Beta Hydroxylase Deficiency |
Drug: Placebo Drug: Droxidopa |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | Phase III, Multi-Center, Study to Assess the Clinical Effect of Droxidopa in Subjects With Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency or Non-Diabetic Neuropathy and Symptomatic NOH |
Estimated Enrollment: | 118 |
Study Start Date: | January 2008 |
Estimated Study Completion Date: | September 2009 |
Primary Completion Date: | August 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Droxidopa: Active Comparator
Double-blind
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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
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Placebo: Placebo Comparator
Double-blind
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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
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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 |
PATIENT INCLUSION CRITERIA:
MAIN PATIENT EXCLUSION CRITERIA:
Principal Investigator: | Horacio Kaufmann, MD | New York University Medical Center |
Principal Investigator: | Christopher J Mathias, MD | Imperial School of Medicine |
Principal Investigator: | Roy Freeman, MD | Harvard Medicine School |
Principal Investigator: | Phillip A Low, MD | Mayo Foundation |
Responsible Party: | Chelsea Therapeutics ( Cameron Szakacs ) |
Study ID Numbers: | Droxidopa 302 |
Study First Received: | March 5, 2008 |
Last Updated: | August 25, 2009 |
ClinicalTrials.gov Identifier: | NCT00633880 History of Changes |
Health Authority: | United States: Food and Drug Administration; Canada: Health Canada; United Kingdom: Medicines and Healthcare Products Regulatory Agency; Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products; Australia: Therapeutic Goods Administration |
NOH Neurogenic Orthostatic Hypotension Orthostatic hypotension PAF Pure Autonomic Failure MSA Multiple System Atrophy |
Neuropathy Autonomic Failure Parkinson Dopamine Deficiency Dopamine Droxidopa |
Hypotension Dopamine Autonomic Nervous System Diseases Hypotension, Orthostatic Multiple System Atrophy Parkinson Disease |
Vascular Diseases Dopamine Agents Droxidopa Postural Hypotension Atrophy Dopamine Beta Hydroxylase Deficiency |
Hypotension Autonomic Nervous System Diseases Hypotension, Orthostatic Anti-Dyskinesia Agents Therapeutic Uses Nervous System Diseases |
Vascular Diseases Antiparkinson Agents Droxidopa Cardiovascular Diseases Central Nervous System Agents Pharmacologic Actions |