Trial Outcomes & Findings for Dose Response to the Norepinephrine Precursor Droxidopa in Hypotensive Individuals With Spinal Cord Injury (NCT NCT03602014)
NCT ID: NCT03602014
Last Updated: 2025-03-07
Results Overview
To determine the proportion (%) of normotensive systolic blood pressure for males=(110-120 mmHg); and females=(101-120 mmHg) following administration of droxidopa.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
22 participants
Primary outcome timeframe
up to 240 minutes following administration of droxidopa
Results posted on
2025-03-07
Participant Flow
Participant milestones
| Measure |
Study 1: Dose Optimization of Northera
Subjects will be administered oral droxidopa in a dose escalation, open-label manner beginning with 200 mg. The dose will be adjusted upwards by 100 mg on subsequent visits until average Systolic Blood Pressure (SBP) recorded 60-120 minutes after dose administration is 111-139 mmHg in males and 101-139 mmHg in females, sustained elevation (≥ 30 consecutive minutes) in seated SBP ≥ 140/100 mmHg, maximum dose of 800 mg is reached without adequate SBP response. Subjects will visit the testing laboratory on as few as 1 (200 mg) and as many as 7 (800 mg) days. Seated cardiovascular assessments will be monitored and recorded at 15-minute intervals for 4-hours, and the side effects questionnaire will be administered hourly during the 4-hour study. Each study visit will take about 5 hours.
Northera: Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
|
Study 2: Blinded Placebo/Northera
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
Northera: Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
Placebo: Study 2 is blinded placebo controlled trial using the individualized optimal dose of droxidopa determined by study 1.
|
Study 2: Blinded Northera/Placebo
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
|---|---|---|---|
|
Overall Study
STARTED
|
15
|
4
|
2
|
|
Overall Study
COMPLETED
|
13
|
4
|
2
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
0
|
Reasons for withdrawal
| Measure |
Study 1: Dose Optimization of Northera
Subjects will be administered oral droxidopa in a dose escalation, open-label manner beginning with 200 mg. The dose will be adjusted upwards by 100 mg on subsequent visits until average Systolic Blood Pressure (SBP) recorded 60-120 minutes after dose administration is 111-139 mmHg in males and 101-139 mmHg in females, sustained elevation (≥ 30 consecutive minutes) in seated SBP ≥ 140/100 mmHg, maximum dose of 800 mg is reached without adequate SBP response. Subjects will visit the testing laboratory on as few as 1 (200 mg) and as many as 7 (800 mg) days. Seated cardiovascular assessments will be monitored and recorded at 15-minute intervals for 4-hours, and the side effects questionnaire will be administered hourly during the 4-hour study. Each study visit will take about 5 hours.
Northera: Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
|
Study 2: Blinded Placebo/Northera
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
Northera: Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
Placebo: Study 2 is blinded placebo controlled trial using the individualized optimal dose of droxidopa determined by study 1.
|
Study 2: Blinded Northera/Placebo
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
0
|
Baseline Characteristics
Dose Response to the Norepinephrine Precursor Droxidopa in Hypotensive Individuals With Spinal Cord Injury
Baseline characteristics by cohort
| Measure |
Study 1: Dose Optimization of Northera
n=13 Participants
Subjects will be administered oral droxidopa in a dose escalation, open-label manner beginning with 200 mg. The dose will be adjusted upwards by 100 mg on subsequent visits until average Systolic Blood Pressure (SBP) recorded 60-120 minutes after dose administration is 111-139 mmHg in males and 101-139 mmHg in females, sustained elevation (≥ 30 consecutive minutes) in seated SBP ≥ 140/100 mmHg, maximum dose of 800 mg is reached without adequate SBP response. Subjects will visit the testing laboratory on as few as 1 (200 mg) and as many as 7 (800 mg) days. Seated cardiovascular assessments will be monitored and recorded at 15-minute intervals for 4-hours, and the side effects questionnaire will be administered hourly during the 4-hour study. Each study visit will take about 5 hours.
Northera: Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
|
Study 2: Blinded Placebo/Northera
n=4 Participants
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
Northera: Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
Placebo: Study 2 is blinded placebo controlled trial using the individualized optimal dose of droxidopa determined by study 1.
|
Study 2: Blinded Northera/Placebo
n=2 Participants
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
42.54 years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
41 years
STANDARD_DEVIATION 13 • n=7 Participants
|
37 years
STANDARD_DEVIATION 2 • n=5 Participants
|
40.65 years
STANDARD_DEVIATION 10.20 • n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
15 Participants
n=4 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
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 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
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 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
|
|
Region of Enrollment
United States
|
13 participants
n=5 Participants
|
4 participants
n=7 Participants
|
2 participants
n=5 Participants
|
19 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: up to 240 minutes following administration of droxidopaTo determine the proportion (%) of normotensive systolic blood pressure for males=(110-120 mmHg); and females=(101-120 mmHg) following administration of droxidopa.
Outcome measures
| Measure |
Study 1: Dose Optimization of Northera
n=1282 Systolic Blood Pressure Recordings
Subjects will be administered oral droxidopa in a dose escalation, open-label manner beginning with 200 mg. The dose will be adjusted upwards by 100 mg on subsequent visits until average Systolic Blood Pressure (SBP) recorded 60-120 minutes after dose administration is 111-139 mmHg in males and 101-139 mmHg in females, sustained elevation (≥ 30 consecutive minutes) in seated SBP ≥ 140/100 mmHg, maximum dose of 800 mg is reached without adequate SBP response. Subjects will visit the testing laboratory on as few as 1 (200 mg) and as many as 7 (800 mg) days. Seated cardiovascular assessments will be monitored and recorded at 15-minute intervals for 4-hours, and the side effects questionnaire will be administered hourly during the 4-hour study. Each study visit will take about 5 hours.
Northera: Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
|
Study 2: Placebo
n=412 Systolic Blood Pressure Recordings
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
Study 2: Northera
n=402 Systolic Blood Pressure Recordings
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
|---|---|---|---|
|
Proportion of Systolic BP Within a Normotensive Range
|
167 Systolic Blood Pressure Recordings
|
117 Systolic Blood Pressure Recordings
|
89 Systolic Blood Pressure Recordings
|
SECONDARY outcome
Timeframe: within 60 minutes of administration of droxidopa or placeboTo measure supine systolic blood pressure following administration of droxidopa compared to placebo in hypotensive participants with SCI
Outcome measures
| Measure |
Study 1: Dose Optimization of Northera
n=15 Participants
Subjects will be administered oral droxidopa in a dose escalation, open-label manner beginning with 200 mg. The dose will be adjusted upwards by 100 mg on subsequent visits until average Systolic Blood Pressure (SBP) recorded 60-120 minutes after dose administration is 111-139 mmHg in males and 101-139 mmHg in females, sustained elevation (≥ 30 consecutive minutes) in seated SBP ≥ 140/100 mmHg, maximum dose of 800 mg is reached without adequate SBP response. Subjects will visit the testing laboratory on as few as 1 (200 mg) and as many as 7 (800 mg) days. Seated cardiovascular assessments will be monitored and recorded at 15-minute intervals for 4-hours, and the side effects questionnaire will be administered hourly during the 4-hour study. Each study visit will take about 5 hours.
Northera: Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
|
Study 2: Placebo
n=6 Participants
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
Study 2: Northera
n=6 Participants
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
|---|---|---|---|
|
Supine Systolic Blood Pressure
|
99.9 mmHg
Standard Deviation 12.3
|
110.9 mmHg
Standard Deviation 10.8
|
107.9 mmHg
Standard Deviation 8.7
|
SECONDARY outcome
Timeframe: 60-90 minutes following administration of droxidopa or placeboPopulation: Participants did not undergo a 70 degree head-up tilt in Study 1 the dose optimization trial.
To document systolic blood pressure responses to head-up tilt to 70 degrees following administration of droxidopa compared to placebo in hypotensive participants with SCI.
Outcome measures
| Measure |
Study 1: Dose Optimization of Northera
Subjects will be administered oral droxidopa in a dose escalation, open-label manner beginning with 200 mg. The dose will be adjusted upwards by 100 mg on subsequent visits until average Systolic Blood Pressure (SBP) recorded 60-120 minutes after dose administration is 111-139 mmHg in males and 101-139 mmHg in females, sustained elevation (≥ 30 consecutive minutes) in seated SBP ≥ 140/100 mmHg, maximum dose of 800 mg is reached without adequate SBP response. Subjects will visit the testing laboratory on as few as 1 (200 mg) and as many as 7 (800 mg) days. Seated cardiovascular assessments will be monitored and recorded at 15-minute intervals for 4-hours, and the side effects questionnaire will be administered hourly during the 4-hour study. Each study visit will take about 5 hours.
Northera: Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
|
Study 2: Placebo
n=6 Participants
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
Study 2: Northera
n=6 Participants
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
|---|---|---|---|
|
Orthostatic Systolic Blood Pressure
|
—
|
99.92 mmHg
Standard Deviation 11.03
|
91.99 mmHg
Standard Deviation 9.85
|
SECONDARY outcome
Timeframe: 60-90 minutes following administration of droxidopa or placeboPopulation: We did not assess middle cerebral artery cerebral blood flow velocity in Study 1 following administration of Northera
To compare cerebral blood flow velocity in the middle cerebral artery following administration of placebo compared to administration of Northera (Droxidopa)
Outcome measures
| Measure |
Study 1: Dose Optimization of Northera
Subjects will be administered oral droxidopa in a dose escalation, open-label manner beginning with 200 mg. The dose will be adjusted upwards by 100 mg on subsequent visits until average Systolic Blood Pressure (SBP) recorded 60-120 minutes after dose administration is 111-139 mmHg in males and 101-139 mmHg in females, sustained elevation (≥ 30 consecutive minutes) in seated SBP ≥ 140/100 mmHg, maximum dose of 800 mg is reached without adequate SBP response. Subjects will visit the testing laboratory on as few as 1 (200 mg) and as many as 7 (800 mg) days. Seated cardiovascular assessments will be monitored and recorded at 15-minute intervals for 4-hours, and the side effects questionnaire will be administered hourly during the 4-hour study. Each study visit will take about 5 hours.
Northera: Study 1 is a dose optimization, open-label trial of Northera from a dose range of 200mg up to 800mg.
|
Study 2: Placebo
n=6 Participants
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
Study 2: Northera
n=6 Participants
Participants will then be administered either oral optimal dose of Northera (Droxidopa) or matching placebo in a double-blinded manner and will remain in the supine position for 60 minutes. Subjects will remain in their wheelchair for instrumentation, which will include: 1) ECG, 2) brachial BP, 3) finger arteriolar BP and 4) Cerebral Blood Flow velocity (CBFv).
|
|---|---|---|---|
|
Orthostatic Cerebral Blood Flow
|
—
|
36.4 cm/sec
Standard Deviation 7.23
|
36.8 cm/sec
Standard Deviation 5.26
|
Adverse Events
Study 1: Dose Optimization of Northera
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Study 2: Northera
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Study 2: Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place