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

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 Dizziness/ Lightheadedness/ Feeling Faint/ or Feeling Like You Might Blackout (OHSA Item 1) [ Time Frame: 14 days ]

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) 14 days following randomization to continued therapy with droxidopa or placebo. [ Time Frame: 14 days ]

Current Secondary Outcome:

• Change in Fatigue (OHSA Item 4) [ Time Frame: 14 days ]
  OHSA item 4 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
• Change in Weakness (OHSA Item 3) [ Time Frame: 14 days ]
  OHSA item 3 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
• Change in Vision (OHSA Item 2) [ Time Frame: 14 days ]
  OHSA item 2 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
• Change in Concentration (OHSA Item 5) [ Time Frame: 14 days ]
  OHSA item 5 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
• Change in Head/Neck Discomfort (OHSA Item 6) [ Time Frame: 14 days ]
  OHSA item 6 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
• Change in Ability to Conduct Activities of Daily Living Score (OHDAS Composite Score) [ Time Frame: 14 days ]
  The OHDAS 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 asks the patient to rate their disease impact over the past week. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
• Change in Orthostatic Hypotension Symptom Assessment Score (OHSA Composite) [ Time Frame: 14 days ]
  The OHSA 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. Each asks the patient to rate their symptoms over the past week. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
• Change in Orthostatic Hypotension Symptom Scores Excluding Dizziness (OHSA Composite Items 2-6) [ Time Frame: 14 days ]
  OHSA composite scale (items 2-6) is the average of five OHSA items: 2) Problems with vision; 3) Weakness; 4) Fatigue; 5) Trouble concentrating; and 6) Head/neck discomfort. Each asks the patient to rate their symptoms over the past week. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe. Change: score at end of study minus score at randomization. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .
• Change in Systolic Blood Pressure (SBP) Measurements 3 Minutes Post Standing; [ Time Frame: 14 days ]
  Change: standing systolic blood pressure at end of study minus standing systolic blood pressure at randomization. In this withdrawal design, a negative score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .

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: 14 days ]
• 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 ]
• 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 ]
• 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 ]

Dates:
Date Received: March 5, 2008
Date Started: January 2008
Date Completion:
Last Updated: April 22, 2014
Last Verified: April 2014