Trial Outcomes & Findings for Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH) (NCT NCT00633880)

NCT ID: NCT00633880

Last Updated: 2014-05-20

Results Overview

OHSA item 1 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) .

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

181 participants

Primary outcome timeframe

14 days

Results posted on

2014-05-20

Participant Flow

Participant milestones

Participant milestones
Measure
Open Label Titration
All patients titrated to their optimal dose of droxidopa during an initial open label phase for 7-14 days
Droxidopa
Double-blind 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
Placebo
Double-blind 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
Open Label Titration
STARTED
181
0
0
Open Label Titration
COMPLETED
101
0
0
Open Label Titration
NOT COMPLETED
80
0
0
Randomized Double Blind
STARTED
0
50
51
Randomized Double Blind
COMPLETED
0
50
51
Randomized Double Blind
NOT COMPLETED
0
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Open Label Titration
All patients titrated to their optimal dose of droxidopa during an initial open label phase for 7-14 days
Droxidopa
Double-blind 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
Placebo
Double-blind 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
Open Label Titration
Lack of Efficacy
1
0
0
Open Label Titration
Adverse Event
13
0
0
Open Label Titration
Treatment Failure
55
0
0
Open Label Titration
Protocol Violation
6
0
0
Open Label Titration
Physician Decision
1
0
0
Open Label Titration
Withdrawal by Subject
4
0
0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Not Randomized
n=80 Participants
Entered open-label droxidopa dose titration, but did not randomize
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=51 Participants
Double-blind 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
Total
n=181 Participants
Total of all reporting groups
Age, Continuous
69.5 years
STANDARD_DEVIATION 9.74 • n=99 Participants
63.1 years
STANDARD_DEVIATION 13.76 • n=107 Participants
66.6 years
STANDARD_DEVIATION 11.25 • n=206 Participants
66.9 years
STANDARD_DEVIATION 11.62 • n=7 Participants
Sex: Female, Male
Female
35 Participants
n=99 Participants
20 Participants
n=107 Participants
19 Participants
n=206 Participants
74 Participants
n=7 Participants
Sex: Female, Male
Male
45 Participants
n=99 Participants
30 Participants
n=107 Participants
32 Participants
n=206 Participants
107 Participants
n=7 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
0 Participants
n=107 Participants
1 Participants
n=206 Participants
1 Participants
n=7 Participants
Race (NIH/OMB)
Asian
0 Participants
n=99 Participants
1 Participants
n=107 Participants
1 Participants
n=206 Participants
2 Participants
n=7 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
White
80 Participants
n=99 Participants
49 Participants
n=107 Participants
49 Participants
n=206 Participants
178 Participants
n=7 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Region of Enrollment
United States
53 participants
n=99 Participants
25 participants
n=107 Participants
32 participants
n=206 Participants
110 participants
n=7 Participants
Region of Enrollment
Canada
8 participants
n=99 Participants
9 participants
n=107 Participants
2 participants
n=206 Participants
19 participants
n=7 Participants
Region of Enrollment
United Kingdom
5 participants
n=99 Participants
3 participants
n=107 Participants
2 participants
n=206 Participants
10 participants
n=7 Participants
Region of Enrollment
Poland
5 participants
n=99 Participants
10 participants
n=107 Participants
8 participants
n=206 Participants
23 participants
n=7 Participants
Region of Enrollment
Australia
8 participants
n=99 Participants
2 participants
n=107 Participants
6 participants
n=206 Participants
16 participants
n=7 Participants
Region of Enrollment
New Zealand
1 participants
n=99 Participants
1 participants
n=107 Participants
1 participants
n=206 Participants
3 participants
n=7 Participants
Primary Clinical Diagnosis
Parkinson's Disease
38 participants
n=99 Participants
21 participants
n=107 Participants
23 participants
n=206 Participants
82 participants
n=7 Participants
Primary Clinical Diagnosis
Multiple System Atrophy
21 participants
n=99 Participants
17 participants
n=107 Participants
13 participants
n=206 Participants
51 participants
n=7 Participants
Primary Clinical Diagnosis
Pure Autonomic Failure
18 participants
n=99 Participants
8 participants
n=107 Participants
10 participants
n=206 Participants
36 participants
n=7 Participants
Primary Clinical Diagnosis
Dopamine Beta-Hydroxylase Deficiency
0 participants
n=99 Participants
0 participants
n=107 Participants
1 participants
n=206 Participants
1 participants
n=7 Participants
Primary Clinical Diagnosis
Non-Diabetic Autonomic Neuropathy
2 participants
n=99 Participants
2 participants
n=107 Participants
3 participants
n=206 Participants
7 participants
n=7 Participants
Primary Clinical Diagnosis
Other
1 participants
n=99 Participants
2 participants
n=107 Participants
1 participants
n=206 Participants
4 participants
n=7 Participants

PRIMARY outcome

Timeframe: 14 days

Population: Missing data were imputed using the last observation carry forward method.

OHSA item 1 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) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=51 Participants
Double-blind 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
Change in Dizziness/ Lightheadedness/ Feeling Faint/ or Feeling Like You Might Blackout (OHSA Item 1)
1.3 units on a scale
Standard Deviation 2.75
1.9 units on a scale
Standard Deviation 3.16

SECONDARY outcome

Timeframe: 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) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=51 Participants
Double-blind 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
Change in Fatigue (OHSA Item 4)
0.7 units on a scale
Standard Deviation 2.61
1.5 units on a scale
Standard Deviation 2.72

SECONDARY outcome

Timeframe: 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) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=51 Participants
Double-blind 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
Change in Weakness (OHSA Item 3)
0.3 units on a scale
Standard Deviation 2.88
1.2 units on a scale
Standard Deviation 2.70

SECONDARY outcome

Timeframe: 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) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=51 Participants
Double-blind 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
Change in Vision (OHSA Item 2)
1.1 units on a scale
Standard Deviation 2.79
0.8 units on a scale
Standard Deviation 2.24

SECONDARY outcome

Timeframe: 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) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=51 Participants
Double-blind 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
Change in Concentration (OHSA Item 5)
0.1 units on a scale
Standard Deviation 2.74
0.9 units on a scale
Standard Deviation 2.67

SECONDARY outcome

Timeframe: 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) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=51 Participants
Double-blind 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
Change in Head/Neck Discomfort (OHSA Item 6)
-0.1 units on a scale
Standard Deviation 2.45
1.2 units on a scale
Standard Deviation 3.19

SECONDARY outcome

Timeframe: 14 days

Population: One placebo patient excluded from analysis because OHDAS values were not evaluable.

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) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=50 Participants
Double-blind 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
Change in Ability to Conduct Activities of Daily Living Score (OHDAS Composite Score)
-0.24 units on a scale
Standard Deviation 2.35
0.91 units on a scale
Standard Deviation 2.50

SECONDARY outcome

Timeframe: 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) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=51 Participants
Double-blind 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
Change in Orthostatic Hypotension Symptom Assessment Score (OHSA Composite)
0.6 units on a scale
Standard Deviation 2.27
1.35 units on a scale
Standard Deviation 2.53

SECONDARY outcome

Timeframe: 14 days

Population: One placebo patient excluded from analysis per the SAP because all baseline values in the composite were zero. LOCF was used to impute values for patients who did not have an end of study visit.

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) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=50 Participants
Double-blind 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
Change in Orthostatic Hypotension Symptom Scores Excluding Dizziness (OHSA Composite Items 2-6)
0.44 units on a scale
Standard Deviation 2.29
1.07 units on a scale
Standard Deviation 2.25

SECONDARY outcome

Timeframe: 14 days

Population: three placebo patients excluded from the analysis due to missing standing blood pressure values at either randomization or end of study.

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) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=50 Participants
Double-blind 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
Placebo
n=48 Participants
Double-blind 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
Change in Systolic Blood Pressure (SBP) Measurements 3 Minutes Post Standing;
-7.6 mmHg
Standard Deviation 19.71
-5.2 mmHg
Standard Deviation 26.83

POST_HOC outcome

Timeframe: 14 days

Population: 3 droxidopa patients and 2 placebo patients were excluded from the analysis due to missing randomization values.

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. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .

Outcome measures

Outcome measures
Measure
Droxidopa
n=47 Participants
Double-blind 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
Placebo
n=49 Participants
Double-blind 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
Change in Orthostatic Hypotension Questionnaire Score (OHQ)
0.11 units on a scale
Standard Deviation 2.176
1.22 units on a scale
Standard Deviation 2.390

Adverse Events

Droxidopa

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Placebo

Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths

Open Label Phase

Serious events: 4 serious events
Other events: 44 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Droxidopa
n=50 participants at risk
Double-blind 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
Placebo
n=51 participants at risk
Double-blind 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
Open Label Phase
n=181 participants at risk
All patient titrated on droxidopa during open-label phase
Cardiac disorders
Coronary artery disease
0.00%
0/50
0.00%
0/51
0.55%
1/181 • Number of events 1
Cardiac disorders
Cardiac failure congestive
0.00%
0/50
0.00%
0/51
0.55%
1/181 • Number of events 1
Infections and infestations
Pneumonia
0.00%
0/50
0.00%
0/51
0.55%
1/181 • Number of events 1
Infections and infestations
Urinary tract infection
0.00%
0/50
2.0%
1/51 • Number of events 1
0.00%
0/181
Blood and lymphatic system disorders
leukopenia
0.00%
0/50
0.00%
0/51
0.55%
1/181 • Number of events 1
Psychiatric disorders
Mental status change
0.00%
0/50
2.0%
1/51 • Number of events 1
0.00%
0/181
Vascular disorders
Orthostatic hypotension
0.00%
0/50
0.00%
0/51
0.55%
1/181 • Number of events 1

Other adverse events

Other adverse events
Measure
Droxidopa
n=50 participants at risk
Double-blind 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
Placebo
n=51 participants at risk
Double-blind 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
Open Label Phase
n=181 participants at risk
All patient titrated on droxidopa during open-label phase
Nervous system disorders
Headache
4.0%
2/50 • Number of events 2
7.8%
4/51 • Number of events 4
11.0%
20/181 • Number of events 28
Nervous system disorders
Dizziness
4.0%
2/50 • Number of events 2
2.0%
1/51 • Number of events 1
8.3%
15/181 • Number of events 18
General disorders
Fatigue
0.00%
0/50
2.0%
1/51 • Number of events 1
5.5%
10/181 • Number of events 10
Injury, poisoning and procedural complications
Fall
2.0%
1/50 • Number of events 2
11.8%
6/51 • Number of events 7
5.0%
9/181 • Number of events 12

Additional Information

Chief Scientific Officer

Chelsea Therapeutics Inc.

Phone: 704-973-4202

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60