Clinical Trial: A Clinical Study for Patients With Neurogenic Orthostatic Hypotension (NOH) Using Droxidopa

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

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 h
Sponsor: Chelsea Therapeutics

Current Primary Outcome: Change in Orthostatic Hypotension Questionnaire Score (OHQ) [ Time Frame: 7 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.

For the change from randomization, negative numbers represent improvement from randomization in OHQ score.



Original Primary Outcome: 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) 7 days following randomization to continued therapy with droxidopa or placebo. [ Time Frame: 7 days ]

Current Secondary Outcome:

  • Change in Ability to Conduct Activities of Daily Living Score (OHDAS Composite Score) [ Time Frame: 7 days ]
    OHDAS composite scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. A negative score indicates an improvement during the double-blind randomized phase relative to value at randomization.
  • Change in Orthostatic Hypotension Symptom Assessment (OHSA Composite) Score [ Time Frame: 7 days ]
    OHSA composite scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. A negative score indicates an improvement during the double-blind randomized phase relative to value at randomization.
  • Change in Activities Involving Standing a Short Time (OHDAS Item 1) [ Time Frame: 7 days ]
    OHDAS Item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. A negative score indicates an improvement during the double-blind randomized phase relative to value at randomization.
  • Change in Activities Involving Walking a Short Time (OHDAS Item 3) [ Time Frame: 7 days ]
    OHDAS Item 3 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. A negative score indicates an improvement during the double-blind randomized phase relative to value at randomization.
  • Change in Dizziness/ Lightheadedness/ Feeling Faint/ or Feeling Like You Might Blackout (OHSA Item 1) [ Time Frame: 7 days ]
    OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. A negative score indicates an improvement during the double-blind randomized phase relative to value at randomization.
  • Patient-Reported Clinical Global Improvement - Severity Scores [ Time Frame: 7 days ]

    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).

  • Clinician-Reported Clinical Global Improvement - Severity Scores [ Time Frame: 7 days ]

    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).

  • Change in Systolic Blood Pressure (SBP) Measurements 3 Minutes Post Standing [ Time Frame: 7 days ]
    Change: standing systolic blood pressure at end of study minus standing systolic blood pressure at randomization. A positive score indicates an improvement during the double-blind randomized phase relative to value at randomization.


Original Secondary Outcome: 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: 7 days ]

Information By: Chelsea Therapeutics

Dates:
Date Received: October 29, 2008
Date Started: September 2008
Date Completion:
Last Updated: April 22, 2014
Last Verified: April 2014