Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH) (NOH302)

This study has been completed.
Chiltern International Inc.
Information provided by (Responsible Party):
Chelsea Therapeutics Identifier:
First received: March 5, 2008
Last updated: March 18, 2013
Last verified: March 2013

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
Symptomatic Neurogenic Orthostatic Hypotension (NOH)
Non-diabetic Neuropathy
Primary Autonomic Failure
Dopamine Beta Hydroxylase Deficiency
Drug: Placebo
Drug: Droxidopa
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Chelsea Therapeutics:

Primary Outcome Measures:
  • To evaluate the efficacy of droxidopa in patients with symptomatic NOH as measured by the relative change in mean score of Item 1 of the (OHSA) 14 days following randomization to continued therapy with droxidopa or placebo. [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate efficacy of droxidopa as measured by changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements 3 minutes post standing; [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Evaluate efficacy of droxidopa by global assessment evaluations using the clinician-recorded and patient-recorded Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scales; [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Evaluate efficacy of droxidopa by symptom and activity measurements using the composite scores of OHSA, OHDAS (the two subcomponents of the Orthostatic Hypotension Questionnaire (OHQ)) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Evaluate the safety of droxidopa based on the occurence of treatment-emergent adverse events and specific evaluation of blood pressure, heart rate, ECG, and laboratory findings across the study [ Time Frame: up to 5 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 118
Study Start Date: January 2008
Study Completion Date: September 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Droxidopa
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
Other Names:
  • L-DOPS
  • L-threo-DOPS
  • Northera
Placebo Comparator: Placebo
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
Other Name: Placebo

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 [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


  • Male or female and aged 18 years or over;
  • Clinical diagnosis of orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA and PAF), Dopamine Beta Hydroxylase Deficiency or Non-Diabetic Autonomic Neuropathies;
  • A documented fall in systolic blood pressure of at least 20 mmHg, or in diastolic blood pressure of at least 10 mmHg, within 3 minutes after standing;
  • 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.


  • Taking ephedrine or midodrine; Patients taking ephedrine or midodrine may enroll after a minimum 7 day washout period;
  • Taking anti-hypertensive medication;
  • Have a history of more than moderate alcohol consumption;
  • Women who are pregnant or lactating;
  • Have a history of closed angle glaucoma;
  • Have 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;
  • In the investigator's opinion, have any other significant systemic, hepatic, cardiac or renal illness;
  • Have diabetes mellitus or insipidus;
  • Have a known or suspected malignancy;
  • Have 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;
  • Have a serum creatinine level > 130 µmol/L;
  Contacts and Locations
Please refer to this study by its identifier: NCT00633880

  Show 54 Study Locations
Sponsors and Collaborators
Chelsea Therapeutics
Chiltern International Inc.
Principal Investigator: Horacio Kaufmann, MD New York University School of Medicine
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
  More Information

Additional Information:
No publications provided

Responsible Party: Chelsea Therapeutics Identifier: NCT00633880     History of Changes
Other Study ID Numbers: Droxidopa NOH302
Study First Received: March 5, 2008
Last Updated: March 18, 2013
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: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Chelsea Therapeutics:
Neurogenic Orthostatic Hypotension
Orthostatic hypotension
Multiple System Atrophy
Pure Autonomic Failure
Autonomic Failure
Dopamine Deficiency

Additional relevant MeSH terms:
Hypotension, Orthostatic
Autonomic Nervous System Diseases
Orthostatic Intolerance
Nervous System Diseases
Central Nervous System Agents
Peripheral Nervous System Agents
Pure Autonomic Failure
Vascular Diseases
Cardiovascular Diseases
Primary Dysautonomias
Antiparkinson Agents
Anti-Dyskinesia Agents
Therapeutic Uses
Pharmacologic Actions
Cardiotonic Agents
Cardiovascular Agents
Autonomic Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents processed this record on April 17, 2014