To evaluate the time to treatment intervention in patients with Parkinson's Disease (PD), Multiple System Atrophy (MSA), Pure Autonomic Failure (PAF), Non-Diabetic Autonomic Neuropathy (NDAN) or Dopamine Beta Hydroxylase (DBH) Deficiency who have been previously stabilized with droxidopa therapy for symptoms of neurogenic orthostatic hypotension (NOH) (dizziness, light-headedness, or feelings that they are about to black out)
This is a multi-site, placebo-controlled, double-blind, randomized withdrawal, time to intervention study with a duration of up to 36 weeks, consisting of 5 periods: Screening Period: up to 4 weeks duration; Open-Label Titration Period (Titration Period): up to 4 weeks duration; Open-Label Treatment Period (Open-Label Period): 12 weeks duration; Double-Blind Treatment Period (Double-Blind Period): 12 weeks duration; Safety Follow-Up Period: 4 weeks duration
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
453
100, 200 or 300 mg
Time To Intervention
Kaplan-Meier estimates are presented for time to treatment intervention. The estimates represent the quartiles of the survival time, where 50% corresponds to the median time to need for treatment intervention. Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Treatment Period: * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) AND lack of efficacy as judged by the investigator; OR * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at 2 consecutive visits; OR * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at the visit before early discontinuation; OR * participant stops IMP or withdraws from study for patient-reported lack of efficacy.
Time frame: Randomization (Day 0) up to Week 12
Number of Participants Who Needed Intervention During the 12-week Double-Blind Treatment Period
Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Treatment Period: * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) AND lack of efficacy as judged by the investigator; OR * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at 2 consecutive visits; OR * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at the visit before early discontinuation; OR * participant stops IMP or withdraws from study for patient-reported lack of efficacy.
Time frame: Randomization (Day 0) up to Week 12
Time To All-cause Discontinuation
Kaplan-Meier estimates are presented for time to all-cause discontinuation. The estimates represent the quartiles of the survival time, where 50% corresponds to the median time to discontinuation. Time to all-cause discontinuation was defined as the time from randomization to withdrawal or last contact date.
Time frame: Randomization (Day 0) up to Week 12
Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score
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MDFirst Research - Chandler
Chandler, Arizona, United States
21st Century Neurology
Phoenix, Arizona, United States
Movement Disorders Center of Arizona
Scottsdale, Arizona, United States
Center For Neurosciences
Tucson, Arizona, United States
Movement Disorder Clinic - The University of Arizona
Tucson, Arizona, United States
University of Arizona Health Sciences Center, Department Of Neurology
Tucson, Arizona, United States
Arkansas Cardiology Clinic
Little Rock, Arkansas, United States
East Bay Physicians Medical Group
Berkeley, California, United States
Sutter East Bay Medical Foundation
Berkeley, California, United States
The Parkinson's and Movement Disorder Institute
Fountain Valley, California, United States
...and 158 more locations
The OHSA scale was designed to rate symptoms occurring specifically as a result of low blood pressure (BP), on average, over the past week using an 11-point scale (0 to 10), with more severe symptoms scoring higher. A score of zero indicates that the symptom was not experienced, and 10 is the worst possible. The scale was used to assess six symptoms: 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. Scores for each activity and a composite score for all six activities were tabulated. A mean negative change from baseline means that symptoms have improved. A mean positive change from baseline means that symptoms have gotten worse.
Time frame: Randomization (Day 0); Weeks 2 to 12
Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score
The OHQ composite score was a mean of the OHSA composite and the Orthostatic Hypotension Daily Activity Scale (OHDAS) composite scores. The OHDAS was designed as a measure of quality of life. It uses an 11-point scale to assess whether orthostatic hypotension (OH) "interfered" with four types of activities: 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. A zero rating means that over the preceding week the activity was performed with no interference and a 10 rating means that orthostatic hypotension completely interfered with the activity. Scores for each activity and a composite score for all four activities were tabulated. A mean negative change from baseline means that symptoms have improved. A mean positive change from baseline means that symptoms have gotten worse.
Time frame: Randomization (Day 0); Weeks 2 to 12
Clinician-rated Clinical Global Impressions - Severity (CGI-S)
The CGI-S was developed to provide global measures of the severity of a participant's clinical condition during clinical studies. The CGI-S was utilized by both the clinician and the participant to provide an impression of the participant's current state of OH. The severity of the participant's current illness was rated by the clinician on a 7-point scale ranging from 1 (normal, no OH) to 7 (among those patients most extremely ill with OH).
Time frame: Weeks 2 to 12
Participant-rated CGI-S
The CGI-S was developed to provide global measures of the severity of a participant's clinical condition during clinical studies. The CGI-S was utilized by both the clinician and the participant to provide an impression of the participant's current state of OH. The severity of the participant's current illness was rated by the participant on a 7-point scale ranging from 1 (normal, no OH) to 7 (most extremely ill with OH).
Time frame: Weeks 2 to 12