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

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ClinicalTrials.gov Identifier: NCT00633880
Recruitment Status : Completed
First Posted : March 12, 2008
Results First Posted : May 20, 2014
Last Update Posted : May 20, 2014
Sponsor:
Collaborator:
Chiltern International Inc.
Information provided by (Responsible Party):
Chelsea Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Symptomatic Neurogenic Orthostatic Hypotension (NOH)
Non-diabetic Neuropathy
Primary Autonomic Failure
Dopamine Beta Hydroxylase Deficiency
Interventions Drug: Placebo
Drug: Droxidopa
Enrollment 181
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Open Label Titration Droxidopa Placebo
Hide Arm/Group Description All patients titrated to their optimal dose of droxidopa during an initial open label phase for 7-14 days

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

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

Period Title: Open Label Titration
Started 181 0 0
Completed 101 0 0
Not Completed 80 0 0
Reason Not Completed
Lack of Efficacy             1             0             0
Adverse Event             13             0             0
Treatment Failure             55             0             0
Protocol Violation             6             0             0
Physician Decision             1             0             0
Withdrawal by Subject             4             0             0
Period Title: Randomized Double Blind
Started 0 50 51
Completed 0 50 51
Not Completed 0 0 0
Arm/Group Title Not Randomized Droxidopa Placebo Total
Hide Arm/Group Description Entered open-label droxidopa dose titration, but did not randomize

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

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 of all reporting groups
Overall Number of Baseline Participants 80 50 51 181
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 80 participants 50 participants 51 participants 181 participants
69.5  (9.74) 63.1  (13.76) 66.6  (11.25) 66.9  (11.62)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 50 participants 51 participants 181 participants
Female
35
  43.8%
20
  40.0%
19
  37.3%
74
  40.9%
Male
45
  56.3%
30
  60.0%
32
  62.7%
107
  59.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 50 participants 51 participants 181 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
1
   2.0%
1
   0.6%
Asian
0
   0.0%
1
   2.0%
1
   2.0%
2
   1.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
80
 100.0%
49
  98.0%
49
  96.1%
178
  98.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 80 participants 50 participants 51 participants 181 participants
United States 53 25 32 110
Canada 8 9 2 19
United Kingdom 5 3 2 10
Poland 5 10 8 23
Australia 8 2 6 16
New Zealand 1 1 1 3
Primary Clinical Diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 80 participants 50 participants 51 participants 181 participants
Parkinson's Disease 38 21 23 82
Multiple System Atrophy 21 17 13 51
Pure Autonomic Failure 18 8 10 36
Dopamine Beta-Hydroxylase Deficiency 0 0 1 1
Non-Diabetic Autonomic Neuropathy 2 2 3 7
Other 1 2 1 4
1.Primary Outcome
Title Change in Dizziness/ Lightheadedness/ Feeling Faint/ or Feeling Like You Might Blackout (OHSA Item 1)
Hide Description 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) .
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
Missing data were imputed using the last observation carry forward method.
Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 50 51
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.3  (2.75) 1.9  (3.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Droxidopa, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.509
Comments Statistical analysis plan involved a hierarchical assessment of secondary endpoints to prevent inflation of type I errors. As the primary endpoint was not positive, statistical analysis was not performed on secondary endpoints.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Secondary Outcome
Title Change in Fatigue (OHSA Item 4)
Hide Description 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) .
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 50 51
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.7  (2.61) 1.5  (2.72)
3.Secondary Outcome
Title Change in Weakness (OHSA Item 3)
Hide Description 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) .
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 50 51
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.3  (2.88) 1.2  (2.70)
4.Secondary Outcome
Title Change in Vision (OHSA Item 2)
Hide Description 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) .
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 50 51
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.1  (2.79) 0.8  (2.24)
5.Secondary Outcome
Title Change in Concentration (OHSA Item 5)
Hide Description 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) .
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 50 51
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.1  (2.74) 0.9  (2.67)
6.Secondary Outcome
Title Change in Head/Neck Discomfort (OHSA Item 6)
Hide Description 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) .
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 50 51
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.1  (2.45) 1.2  (3.19)
7.Secondary Outcome
Title Change in Ability to Conduct Activities of Daily Living Score (OHDAS Composite Score)
Hide Description 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) .
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
One placebo patient excluded from analysis because OHDAS values were not evaluable.
Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 50 50
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.24  (2.35) 0.91  (2.50)
8.Secondary Outcome
Title Change in Orthostatic Hypotension Symptom Assessment Score (OHSA Composite)
Hide Description 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) .
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 50 51
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.6  (2.27) 1.35  (2.53)
9.Secondary Outcome
Title Change in Orthostatic Hypotension Symptom Scores Excluding Dizziness (OHSA Composite Items 2-6)
Hide Description 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) .
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description

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.

Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 50 50
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.44  (2.29) 1.07  (2.25)
10.Secondary Outcome
Title Change in Systolic Blood Pressure (SBP) Measurements 3 Minutes Post Standing;
Hide Description 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) .
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
three placebo patients excluded from the analysis due to missing standing blood pressure values at either randomization or end of study.
Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 50 48
Mean (Standard Deviation)
Unit of Measure: mmHg
-7.6  (19.71) -5.2  (26.83)
11.Post-Hoc Outcome
Title Change in Orthostatic Hypotension Questionnaire Score (OHQ)
Hide Description

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) .

Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
3 droxidopa patients and 2 placebo patients were excluded from the analysis due to missing randomization values.
Arm/Group Title Droxidopa Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 47 49
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.11  (2.176) 1.22  (2.390)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Droxidopa, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Droxidopa Placebo Open Label Phase
Hide Arm/Group Description

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

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

All patient titrated on droxidopa during open-label phase
All-Cause Mortality
Droxidopa Placebo Open Label Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Droxidopa Placebo Open Label Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/50 (0.00%)      1/51 (1.96%)      4/181 (2.21%)    
Blood and lymphatic system disorders       
leukopenia  0/50 (0.00%)  0 0/51 (0.00%)  0 1/181 (0.55%)  1
Cardiac disorders       
Coronary artery disease  0/50 (0.00%)  0 0/51 (0.00%)  0 1/181 (0.55%)  1
Cardiac failure congestive  0/50 (0.00%)  0 0/51 (0.00%)  0 1/181 (0.55%)  1
Infections and infestations       
Pneumonia  0/50 (0.00%)  0 0/51 (0.00%)  0 1/181 (0.55%)  1
Urinary tract infection  0/50 (0.00%)  0 1/51 (1.96%)  1 0/181 (0.00%)  0
Psychiatric disorders       
Mental status change  0/50 (0.00%)  0 1/51 (1.96%)  1 0/181 (0.00%)  0
Vascular disorders       
Orthostatic hypotension  0/50 (0.00%)  0 0/51 (0.00%)  0 1/181 (0.55%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Droxidopa Placebo Open Label Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/50 (8.00%)      11/51 (21.57%)      44/181 (24.31%)    
General disorders       
Fatigue  0/50 (0.00%)  0 1/51 (1.96%)  1 10/181 (5.52%)  10
Injury, poisoning and procedural complications       
Fall  1/50 (2.00%)  2 6/51 (11.76%)  7 9/181 (4.97%)  12
Nervous system disorders       
Headache  2/50 (4.00%)  2 4/51 (7.84%)  4 20/181 (11.05%)  28
Dizziness  2/50 (4.00%)  2 1/51 (1.96%)  1 15/181 (8.29%)  18
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Scientific Officer
Organization: Chelsea Therapeutics Inc.
Phone: 704-973-4202
EMail: hewitt@chelsearx.com
Layout table for additonal information
Responsible Party: Chelsea Therapeutics
ClinicalTrials.gov Identifier: NCT00633880     History of Changes
Other Study ID Numbers: Droxidopa NOH302
First Submitted: March 5, 2008
First Posted: March 12, 2008
Results First Submitted: March 18, 2014
Results First Posted: May 20, 2014
Last Update Posted: May 20, 2014