Trial Outcomes & Findings for A Two Part Study (306A/306B) to Assess Droxidopa in Treatment of NOH in Patients With Parkinson's Disease (NCT NCT01176240)

NCT ID: NCT01176240

Last Updated: 2014-05-20

Results Overview

The primary efficacy endpoint for 306A is the relative mean change in Orthostatic Hypotension Questionnaire (OHQ) composite score from baseline to end of study. 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 baseline, negative numbers represent improvement from baseline in OHQ score.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 225 participants
• Primary outcome timeframe: Baseline, Week 8
• Results posted on: 2014-05-20

Participant Flow

Post-randomization, up to 2 weeks dose titration followed by 8 wks at optimal dose. The first 51 patients enrolled in the study were analyzed as a separate group in an interim analysis (Study 306A). The final 171 patients remained blinded until the end of the study and analyzed as a separate study (Study 306B).

Participant milestones

Measure	Droxidopa droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo Placebo matched control Placebo: Placebo
Study 306A STARTED	24	27
Study 306A COMPLETED	21	24
Study 306A NOT COMPLETED	3	3
Study 306B STARTED	89	85
Study 306B Took at Least 1 Dose of Study Drug	87	84
Study 306B 1 wk of Stable Dosing and Visit 4	69	78
Study 306B 2 wk of Stable Dosing and Visit 5	68	75
Study 306B 4 wk of Stable Dosing and Visit 6	67	73
Study 306B COMPLETED	63	68
Study 306B NOT COMPLETED	26	17

Reasons for withdrawal

Measure	Droxidopa droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo Placebo matched control Placebo: Placebo
Study 306A Lack of Efficacy	2	1
Study 306A Protocol Violation	0	1
Study 306A Withdrawal by Subject	0	1
Study 306A Stop due to diverse problems	1	0
Study 306B Lack of Efficacy	5	3
Study 306B Adverse Event	10	5
Study 306B Protocol Violation	2	3
Study 306B Withdrawal by Subject	4	1
Study 306B Physician Decision	2	1
Study 306B Supine Hypertension	1	2
Study 306B Lost to Follow-up	0	1
Study 306B withdrew prior to dosing	2	1

Baseline Characteristics

A Two Part Study (306A/306B) to Assess Droxidopa in Treatment of NOH in Patients With Parkinson's Disease

Baseline characteristics by cohort

Measure	Study 306A: Droxidopa n=24 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Study 306A: Placebo n=27 Participants Placebo matched control Placebo: Placebo	Study 306B: Droxidopa n=87 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Study 306B: Placebo n=84 Participants Placebo matched control Placebo: Placebo	Total n=222 Participants Total of all reporting groups
Age, Continuous	72.2 years STANDARD_DEVIATION 7.30 • n=5 Participants	72.9 years STANDARD_DEVIATION 7.76 • n=7 Participants	72.5 years STANDARD_DEVIATION 7.64 • n=5 Participants	72.2 years STANDARD_DEVIATION 7.97 • n=4 Participants	72.4 years STANDARD_DEVIATION 7.78 • n=21 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	10 Participants n=7 Participants	27 Participants n=5 Participants	30 Participants n=4 Participants	77 Participants n=21 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	17 Participants n=7 Participants	60 Participants n=5 Participants	54 Participants n=4 Participants	145 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants	25 Participants n=7 Participants	84 Participants n=5 Participants	83 Participants n=4 Participants	216 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	24 participants n=5 Participants	27 participants n=7 Participants	87 participants n=5 Participants	84 participants n=4 Participants	222 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: LOCF was used to impute values for patients who did not have an end of study visit.

The primary efficacy endpoint for 306A is the relative mean change in Orthostatic Hypotension Questionnaire (OHQ) composite score from baseline to end of study. 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 baseline, negative numbers represent improvement from baseline in OHQ score.

Outcome measures

Measure	Droxidopa n=24 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo n=27 Participants Placebo matched control Placebo: Placebo
306A Efficacy: Change in Orthostatic Hypotension Questionnaire Score (OHQ)	-2.2 units on a scale Standard Deviation 2.44	-2.1 units on a scale Standard Deviation 2.49

PRIMARY outcome

Timeframe: Baseline, Week1

Population: The primary analysis was defined as those patients who completed 1 week of dosing at the identified optimal dose of study medication and completed the visit 4 (1 week) efficacy evaluation. Patients who did not have week 1 efficacy data were excluded from the analysis.

OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at Week 1 minus score at baseline. A negative score indicates an improvement in symptoms during the double-blind randomized phase relative to value at baseline.

Outcome measures

Measure	Droxidopa n=69 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo n=78 Participants Placebo matched control Placebo: Placebo
306B Efficacy: Change in Dizziness/Lightheadedness/Feeling Faint/Feeling Like You Might Black Out (OHSA Item 1)	-2.3 units on a scale Standard Deviation 2.95	-1.3 units on a scale Standard Deviation 3.16

SECONDARY outcome

Timeframe: Baseline, Week2

OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at Week 2 minus score at baseline. A negative score indicates an improvement in symptoms during the double-blind randomized phase relative to value at baseline.

Outcome measures

Measure	Droxidopa n=68 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo n=75 Participants Placebo matched control Placebo: Placebo
306B Efficacy: Change in OHSA Item 1 From Baseline to Week 2 (Visit 5)	-1.9 units on a scale Standard Deviation 2.86	-1.6 units on a scale Standard Deviation 2.97

SECONDARY outcome

Timeframe: Baseline, Week4

OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at Week 4 minus score at baseline. A negative score indicates an improvement in symptoms during the double-blind randomized phase relative to value at baseline.

Outcome measures

Measure	Droxidopa n=67 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo n=73 Participants Placebo matched control Placebo: Placebo
306B Efficacy: Change in OHSA Item 1 From Baseline to Week 4 (Visit 6)	-2.0 units on a scale Standard Deviation 3.08	-1.5 units on a scale Standard Deviation 2.74

SECONDARY outcome

Timeframe: Baseline, Week 1

Population: One droxidopa patient did not complete the standing blood pressure measurements of the orthostatic standing test at visit 4 (one week of stable dosing)

Measure: Lowest standing systolic blood pressure reading of immediately post standing and 3 minutes post standing. Change: standing systolic blood pressure at Week 1 (Visit 4) minus standing systolic blood pressure at baseline. A positive score indicates an improvement in standing systolic blood pressure during the double-blind randomized phase relative to value at baseline.

Outcome measures

Measure	Droxidopa n=68 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo n=78 Participants Placebo matched control Placebo: Placebo
306B Efficacy: Change in Systolic Blood Pressure (SBP) Measurements Post Standing From Baseline to Week 1	6.4 mmHg Standard Deviation 18.85	0.7 mmHg Standard Deviation 20.18

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The analysis was defined as those patients who completed 8 week of dosing and completed the visit 7 (8 week) efficacy evaluation. Patients who did not have week 8 efficacy data were excluded from the analysis. Of note, 2 patients completed the 8 week double blind study, but did not complete the efficacy evaluations at the final visit.

OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at Week 8 minus score at baseline. A negative score indicates an improvement in symptoms during the double-blind randomized phase relative to value at baseline.

Outcome measures

Measure	Droxidopa n=63 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo n=68 Participants Placebo matched control Placebo: Placebo
306B Efficacy: Change in OHSA Item 1 From Baseline to Week 8 (Visit 7)	-2.1 units on a scale Standard Deviation 3.03	-1.5 units on a scale Standard Deviation 2.91

SECONDARY outcome

Timeframe: up to 10 weeks

Population: The primary analysis was defined as those patients who completed 1 week of dosing at the identified optimal dose of study medication and completed the visit 4 (1 week) efficacy evaluation. Patients who did not have week 1 efficacy data were excluded from the analysis.

The average number of patient reported falls per week.

Outcome measures

Measure	Droxidopa n=69 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo n=78 Participants Placebo matched control Placebo: Placebo
306B Efficacy: Rate of Patient Reported Falls	0.4 falls per week Standard Deviation 0.84	2.0 falls per week Standard Deviation 12.95

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: The primary analysis was defined as those patients who completed 8 week of dosing and completed the visit 7 (8 week) efficacy evaluation. Patients who did not have week 8 efficacy data were excluded from the analysis. Of note, 2 patients completed the 8 week double blind study, but did not complete the efficacy evaluations at the final visit.

The relative mean change in Orthostatic Hypotension Questionnaire (OHQ) composite score from baseline to end of study. 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 baseline, negative numbers represent improvement from baseline in OHQ score.

Outcome measures

Measure	Droxidopa n=63 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo n=68 Participants Placebo matched control Placebo: Placebo
306B Efficacy: Change in Orthostatic Hypotension Questionnaire Score (OHQ)	-2.2 units on a scale Standard Deviation 2.29	-2.0 units on a scale Standard Deviation 2.18

POST_HOC outcome

Timeframe: Baseline, Week 8

The total number of patient reported falls during the 8 week treatment period

Outcome measures

Measure	Droxidopa n=24 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo n=27 Participants Placebo matched control Placebo: Placebo
306A Efficacy: Patient Reported Falls	79 total falls per group	192 total falls per group

POST_HOC outcome

Timeframe: Baseline, Week 1

Population: Last observation carried forward was used to impute missing values.

OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at Week 1 minus score at baseline. A negative score indicates improvement in symptoms during the double-blind randomized phase relative to value at baseline.

Outcome measures

Measure	Droxidopa n=24 Participants droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment	Placebo n=27 Participants Placebo matched control Placebo: Placebo
Study 306A: Change in Dizziness/Lightheadedness/Feeling Faint/Feeling Like You Might Black Out (OHSA Item 1) From Baseline to Week 1	-3.1 units on a scale Standard Deviation 3.39	-1.6 units on a scale Standard Deviation 3.12

Adverse Events

Droxidopa

Serious events: 5 serious events

Other events: 54 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Measure	Droxidopa n=114 participants at risk droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment Droxidopa Safety set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa for short periods of time during the trial.	Placebo n=108 participants at risk Placebo matched control Placebo: Placebo Placebo Safety set excludes 3 patients randomized to placebo who were mistakenly dosed with droxidopa for short periods of time during the trial.
Gastrointestinal disorders Abdominal pain upper	0.88% 1/114 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.00% 0/108 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Gastrointestinal disorders Faecaloma	0.88% 1/114 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.00% 0/108 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Gastrointestinal disorders Inguinal hernia	0.88% 1/114 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.00% 0/108 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Cardiac disorders Atrial fibrillation	0.88% 1/114 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.00% 0/108 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Infections and infestations Bronchitis viral	0.88% 1/114 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.00% 0/108 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Infections and infestations Upper respiratory tract infection bacterial	0.88% 1/114 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.00% 0/108 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Infections and infestations Viral infection	0.00% 0/114 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.93% 1/108 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Nervous system disorders Presyncope	0.88% 1/114 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.00% 0/108 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Nervous system disorders Syncope	0.00% 0/114 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	1.9% 2/108 • Number of events 2 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Psychiatric disorders Mental status changes	0.88% 1/114 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.00% 0/108 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Vascular disorders Hypertension	0.88% 1/114 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.00% 0/108 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
General disorders Asthenia	0.00% 0/114 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.93% 1/108 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/114 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.93% 1/108 • Number of events 1 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.

Other adverse events

Measure	Droxidopa n=114 participants at risk droxidopa active drug Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment Droxidopa Safety set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa for short periods of time during the trial.	Placebo n=108 participants at risk Placebo matched control Placebo: Placebo Placebo Safety set excludes 3 patients randomized to placebo who were mistakenly dosed with droxidopa for short periods of time during the trial.
Nervous system disorders Headache	13.2% 15/114 • Number of events 19 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	7.4% 8/108 • Number of events 8 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Nervous system disorders Dizziness	9.6% 11/114 • Number of events 13 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	4.6% 5/108 • Number of events 6 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Gastrointestinal disorders Nausea	8.8% 10/114 • Number of events 13 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	4.6% 5/108 • Number of events 5 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Gastrointestinal disorders Diarrhoea	3.5% 4/114 • Number of events 4 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	7.4% 8/108 • Number of events 9 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
General disorders Fatigue	7.0% 8/114 • Number of events 8 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	5.6% 6/108 • Number of events 7 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
General disorders Oedema peripheral	4.4% 5/114 • Number of events 5 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	5.6% 6/108 • Number of events 6 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Injury, poisoning and procedural complications Contusion	5.3% 6/114 • Number of events 7 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	11.1% 12/108 • Number of events 14 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Injury, poisoning and procedural complications Excoriation	5.3% 6/114 • Number of events 6 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	7.4% 8/108 • Number of events 8 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Injury, poisoning and procedural complications Skin laceration	4.4% 5/114 • Number of events 10 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	9.3% 10/108 • Number of events 15 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Vascular disorders Hypertension	6.1% 7/114 • Number of events 10 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	0.93% 1/108 • Number of events 2 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.
Investigations Blood pressure increased	3.5% 4/114 • Number of events 9 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.	6.5% 7/108 • Number of events 7 Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC. Only dosed patients included in Safety Set. Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.

Additional Information

Chief Scientific Officer

Chelsea Therapeutics Inc.

Phone: 704-973-4202

Email: hewitt@chelsearx.com

Results disclosure agreements

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

Restriction type: LTE60