Open-Label Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)

Last updated: April 22, 2014
Sponsor: Chelsea Therapeutics
Overall Status: Completed

Phase

3

Condition

Dizzy/fainting Spells

Circulation Disorders

Multiple System Atrophy

Treatment

N/A

Clinical Study ID

NCT00738062
Droxidopa NOH303
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria: 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 theymay withdraw their consent at any time without prejudice to their future medical care.

Exclusion

Exclusion Criteria: Patients are not eligible for this study if they fulfill one or more of the followingcriteria:

  • Currently taking ephedrine or midodrine;

  • Patients taking ephedrine or midodrine must stop taking these drugs at least 2 daysprior 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 norepinephrinere-uptake inhibitors;

  • Have changed dose, frequency and or type of prescribed medication, within two weeks ofstudy 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 12consecutive 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), hormonalcontraceptives (oral, depot, patch or injectable) and double barrier methods suchas 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 periodand for 30 days after the last dose of investigational product.

  • If hormonal contraceptives are used they should be taken according to the packageinsert.

  • WOCP who are not currently sexually active must agree to use acceptablecontraception, as defined above, if they decide to become sexually active duringthe period of the study and for 30 days after the last dose of investigationalproduct.

  • Sexually active males whose partner is a WOCP and who do not agree to use condoms forthe 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 significantcardiac 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 thatmay, in the investigator's opinion, affect the absorption of study drug;

  • In the investigator's opinion, have clinically significant abnormalities on clinicalexamination or laboratory testing;

  • In the investigator's opinion, are unable to adequately co-operate because ofindividual or family situation;

  • In the investigator's opinion, are suffering from a mental disorder that interfereswith the diagnosis and/or with the conduct of the study, e.g. schizophrenia, majordepression, dementia;

  • Are not able or willing to comply with the study requirements for the duration of thestudy.

Study Design

Total Participants: 103
Study Start date:
January 01, 2008
Estimated Completion Date:
December 31, 2010

Study 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.

Connect with a study center

  • Royal Adelaide Hospital

    Adelaide, South Australia 5000
    Australia

    Site Not Available

  • Baker Heart Research Institute

    Melbourne, Victoria 3004
    Australia

    Site Not Available

  • Austin Hospital

    Heidelburg, 3084
    Australia

    Site Not Available

  • McMaster University

    Hamilton, Ontario L8L2X2
    Canada

    Site Not Available

  • Centre for Movement Disorders

    Markham, Ontario L6B1C9
    Canada

    Site Not Available

  • Parkinson's & Neurodegenerative Disorders Clinic

    Ottawa, Ontario K1G4G3
    Canada

    Site Not Available

  • SMBD Jewish General Hospital - Department of Neurology

    Montreal, Quebec H3T 1E2
    Canada

    Site Not Available

  • Quebec Memory and Motor Skills Disorders Clinic

    Quebec, G1R 3X5
    Canada

    Site Not Available

  • Auckland Hospital

    Grafton Auckland, Private Bag
    New Zealand

    Site Not Available

  • Van der Veer Institute for Parkinson's Disease and Movement Disorders

    Christchurch,
    New Zealand

    Site Not Available

  • University of Alabama at Birmingham

    Birmingham, Alabama 35233
    United States

    Site Not Available

  • Dedicated Clinical Research

    Litchfield Park, Arizona 85340
    United States

    Site Not Available

  • Xenoscience Inc.

    Phoenix, Arizona 85004
    United States

    Site Not Available

  • Sun Health Research Institute

    Sun City, Arizona 85351
    United States

    Site Not Available

  • The Parkinson's and Movement Disorders Institute

    Fountain Valley, California 92708
    United States

    Site Not Available

  • Pacific Neuroscience Medical Group

    Oxnard, California 93030
    United States

    Site Not Available

  • The Parkinson's Institute

    Sunnyvale, California 94085
    United States

    Site Not Available

  • Electrophysiology Associates

    Colorado Springs, Colorado 80910
    United States

    Site Not Available

  • Parkinson's Disease & Movment Disorder Center

    Boca Raton, Florida 33486
    United States

    Site Not Available

  • Southeastern Integrated Medical

    Gainesville, Florida 32607
    United States

    Site Not Available

  • Mayo Jacksonville Florida Department of Neurology

    Jacksonville, Florida 32224
    United States

    Site Not Available

  • University of Miami Miller School of Medicine

    Miami, Florida 33136
    United States

    Site Not Available

  • University of South Florida

    Tampa, Florida 33606
    United States

    Site Not Available

  • Medical Associates of North Georgia

    Canton, Georgia 30114
    United States

    Site Not Available

  • Saint Mary of Nazareth Hospital Center

    Chicago, Illinois 60622
    United States

    Site Not Available

  • North Chicago VA Medical Center

    North Chicago, Illinois 60064
    United States

    Site Not Available

  • Indiana Medical Research

    Elkhart, Indiana 46514
    United States

    Site Not Available

  • JWM Neurology

    Indianapolis, Indiana 46237
    United States

    Site Not Available

  • Kansas City Bone and Joint, PA

    Overland Park, Kansas 66211
    United States

    Site Not Available

  • University of Louisville

    Louisville, Kentucky 40202
    United States

    Site Not Available

  • University of Maryland Hospital

    Baltimore, Maryland 21201
    United States

    Site Not Available

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts 02215
    United States

    Site Not Available

  • University of Massachusetts Worcester

    Worcester, Massachusetts 01655
    United States

    Site Not Available

  • Henry Ford Health System

    Southfield, Michigan 48034
    United States

    Site Not Available

  • Mayo Clinic Rochester

    Rochester, Minnesota 55905
    United States

    Site Not Available

  • Washington University Medical Center

    St. Louis, Missouri 63110
    United States

    Site Not Available

  • New Jersey Neuroscience Institute

    Edison, New Jersey 08818
    United States

    Site Not Available

  • Kingston Neurological Associates, PC

    Kingston, New York 12401
    United States

    Site Not Available

  • Columbia University Neurological institute of NY

    New York, New York 10032
    United States

    Site Not Available

  • NYU Medical Center

    New York City, New York 10016
    United States

    Site Not Available

  • University of Rochester

    Rochester, New York 14618
    United States

    Site Not Available

  • Duke University Medical Center

    Durham, North Carolina 27705
    United States

    Site Not Available

  • Wake Forest University

    Winston Salem, North Carolina 27157
    United States

    Site Not Available

  • University of Cincinnati

    Cincinnati, Ohio 45267
    United States

    Site Not Available

  • Cleveland Clinic

    Cleveland, Ohio 44195
    United States

    Site Not Available

  • University Hospitals Case Medical Center

    Cleveland, Ohio 44106
    United States

    Site Not Available

  • COR Clinical Research, LLC

    Oklahoma City, Oklahoma 73103
    United States

    Site Not Available

  • The Oregon Clinic

    Portland, Oregon 97213
    United States

    Site Not Available

  • Vanderbilt University

    Nashville, Tennessee 37212
    United States

    Site Not Available

  • Jacinto Medical Group, PA

    Baytown, Texas 77521
    United States

    Site Not Available

  • UT Southwestern Medical Center

    Dallas, Texas 75390-9036
    United States

    Site Not Available

  • Scott & White Healthcare - Round Rock

    Round Rock, Texas 78665
    United States

    Site Not Available

  • Scott & White Memorial Hospital & Clinic

    Temple, Texas 76508
    United States

    Site Not Available

  • East Texas Medical Center - Neurological Institute Movment Disorders Center

    Tyler, Texas 75701
    United States

    Site Not Available

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