Trial Outcomes & Findings for NORTHERA (DROXIDOPA) for Dysautonomia in Adult Survivors of Menkes Disease and Occipital Horn Syndrome (NCT NCT04977388)
NCT ID: NCT04977388
Last Updated: 2026-04-13
Results Overview
Treatment related adverse events as assessed by CTCAE v 4.0 by study arm
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
3 participants
Primary outcome timeframe
TEAEs in 6 week periods of either active drug (droxidopa) or placebo
Results posted on
2026-04-13
Participant Flow
Three adult participants were consented and screened for eligibility between July 2021 and October 2023.
Three Adult participants were assigned randomly to receive either Northera (droxidopa) then placebo placebo (Arm 1) or Placebo then Northera (droxidopa) (Arm 2). An open label dose titration was utilized in advance to determine each participant's maximally tolerated dose (100, 200, or 300mg) of droxidopa. Participants then underwent a 7 to 10 day washout period prior to beginning the treatment arms. There was also a washout period of 7 to 10 days between each of the two treatment arms.
Participant milestones
| Measure |
Arm 1 (Northera™ (Droxidopa) First Then Placebo)
Participants in Arm 1 received Northera (Droxidopa) first then placebo based on prior randomization. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0); the placebo capsules were empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline. Capsules of Northera/Droxidopa were physically indistinguishable from the Placebo capsules. Frequency of administration (by mouth) was twice daily for six weeks.
Partcipants self-administered capsules of Northera (Droxidopa) or Placebo by mouth twice daily for six weeks.
|
Arm 2- Placebo First Then Northera (Droxidopa)
Participants in Arm 2 received Placebo first then Northera (Droxidopa) based on prior randomization. The placebo capsules were empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0); Capsules of Northera/Droxidopa were physically indistinguishable from the Placebo capsules. Frequency of administration (by mouth) was twice daily for six weeks.
Partcipants self-administered capsules of Northera (Droxidopa) or Placebo by mouth twice daily for six weeks.
|
|---|---|---|
|
First Intervention (6 weeks)
STARTED
|
1
|
2
|
|
First Intervention (6 weeks)
COMPLETED
|
1
|
2
|
|
First Intervention (6 weeks)
NOT COMPLETED
|
0
|
0
|
|
Washout (7-10 days)
STARTED
|
1
|
2
|
|
Washout (7-10 days)
COMPLETED
|
1
|
2
|
|
Washout (7-10 days)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention (6 weeks)
STARTED
|
1
|
2
|
|
Second Intervention (6 weeks)
COMPLETED
|
1
|
2
|
|
Second Intervention (6 weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
NORTHERA (DROXIDOPA) for Dysautonomia in Adult Survivors of Menkes Disease and Occipital Horn Syndrome
Baseline characteristics by cohort
| Measure |
Northera (Droxidopa) First Then Placebo
n=1 Participants
Participants received Northera (droxidopa) first then Placebo. Northera (Droxidopa) was provided to adult subjects as a capsule with 100mg, 200mg, or 300mg of Northera (Droxidopa) contained within gelatin color capsules (sky blue and white, size 0) based on findings from the dose titration visit. These capsules are physically indistinguishable from the placebo capsules. Frequency of administration (by mouth) was twice daily for six weeks.
Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Frequency of administration (by mouth) will be twice daily for six weeks
|
Placebo First Then Northera (Droxidopa)
n=2 Participants
Participants received Placebo first then Northera (droxidopa). Northera (Droxidopa) was provided to adult subjects as a capsule with 100mg, 200mg, or 300mg of Northera (Droxidopa) contained within gelatin color capsules (sky blue and white, size 0) based on findings from the dose titration visit. These capsules are physically indistinguishable from the placebo capsules. Frequency of administration (by mouth) was twice daily for six weeks.Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Frequency of administration (by mouth) will be twice daily for six weeks.
|
Total
n=3 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race (NIH/OMB)
White
|
1 Participants
n=193 Participants
|
1 Participants
n=193 Participants
|
2 Participants
n=386 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=193 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=386 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=193 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=386 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=193 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=386 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=193 Participants
|
1 Participants
n=193 Participants
|
2 Participants
n=386 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=193 Participants
|
1 Participants
n=193 Participants
|
1 Participants
n=386 Participants
|
|
Region of Enrollment
United States
|
1 Participants
n=193 Participants
|
2 Participants
n=193 Participants
|
3 Participants
n=386 Participants
|
|
Height
|
166.2 cm
n=193 Participants
|
174.85 cm
n=193 Participants
|
171.97 cm
n=386 Participants
|
|
Weight
|
68.0 kg
n=193 Participants
|
52.6 kg
n=193 Participants
|
57.73 kg
n=386 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=193 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=386 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=193 Participants
|
2 Participants
n=193 Participants
|
3 Participants
n=386 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=193 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=386 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=193 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=386 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=193 Participants
|
2 Participants
n=193 Participants
|
3 Participants
n=386 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=193 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=386 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=193 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=386 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=193 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=386 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=193 Participants
|
1 Participants
n=193 Participants
|
1 Participants
n=386 Participants
|
PRIMARY outcome
Timeframe: TEAEs in 6 week periods of either active drug (droxidopa) or placeboTreatment related adverse events as assessed by CTCAE v 4.0 by study arm
Outcome measures
| Measure |
Northera (Droxidopa)
n=3 Participants
This group includes all three participants who received Northera (Droxidopa) during the entire course of this crossover study. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0).
Participants self-administered capsules of Northera (Droxidopa) by mouth twice daily for six weeks during this crossover study.
|
Placebo
n=3 Participants
This group includes all three participants who received placebo during the entire course of this crossover study. Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Participants self-administered capsules of placebo by mouth twice daily for six weeks during this crossover study.
|
|---|---|---|
|
Treatment Related Adverse Events as Assessed by CTCAE v4.0
|
10 adverse events
|
6 adverse events
|
SECONDARY outcome
Timeframe: Change in systolic BP in tilt position during each 6 week treatment arm (droxidopa and placebo) compared to baseline.Change in systolic BP in tilt position during each treatment arm (droxidopa and placebo) compared to baseline.
Outcome measures
| Measure |
Northera (Droxidopa)
n=3 Participants
This group includes all three participants who received Northera (Droxidopa) during the entire course of this crossover study. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0).
Participants self-administered capsules of Northera (Droxidopa) by mouth twice daily for six weeks during this crossover study.
|
Placebo
n=3 Participants
This group includes all three participants who received placebo during the entire course of this crossover study. Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Participants self-administered capsules of placebo by mouth twice daily for six weeks during this crossover study.
|
|---|---|---|
|
Mean Change in Systolic Blood Pressure in Tilt Position
|
-25 mm/Hg
Standard Error 12.5 • Interval 29.1 to 83.2
|
-22 mm/Hg
Standard Error 6.5 • Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: The change in diastolic BP in tilt position during each 6 week treatment arm (droxidopa and placebo) compared to baseline.The change in diastolic BP in tilt position during each treatment arm (droxidopa and placebo) compared to baseline.
Outcome measures
| Measure |
Northera (Droxidopa)
n=3 Participants
This group includes all three participants who received Northera (Droxidopa) during the entire course of this crossover study. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0).
Participants self-administered capsules of Northera (Droxidopa) by mouth twice daily for six weeks during this crossover study.
|
Placebo
n=3 Participants
This group includes all three participants who received placebo during the entire course of this crossover study. Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Participants self-administered capsules of placebo by mouth twice daily for six weeks during this crossover study.
|
|---|---|---|
|
Mean Change in Diastolic Blood Pressure in Tilt Position
|
-8.6 mmHg
Standard Error 7.5 • Interval 16.3 to 38.1
|
-15 mmHg
Standard Error 4.5 • Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Change in plasma catechols between each 6 week treatment arm (droxidopa and placebo)Change in plasma catechols between placebo and droxidopa treatment arms
Outcome measures
| Measure |
Northera (Droxidopa)
n=3 Participants
This group includes all three participants who received Northera (Droxidopa) during the entire course of this crossover study. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0).
Participants self-administered capsules of Northera (Droxidopa) by mouth twice daily for six weeks during this crossover study.
|
Placebo
n=3 Participants
This group includes all three participants who received placebo during the entire course of this crossover study. Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Participants self-administered capsules of placebo by mouth twice daily for six weeks during this crossover study.
|
|---|---|---|
|
Plasma Catechol Levels
|
65 pg/ml
Standard Error 8
|
20 pg/ml
Standard Error 4
|
SECONDARY outcome
Timeframe: Change from baseline in daily bowel movements per day during each 6 week treatment arm (droxidopa and placebo).Change from baseline in daily bowel movements
Outcome measures
| Measure |
Northera (Droxidopa)
n=3 Participants
This group includes all three participants who received Northera (Droxidopa) during the entire course of this crossover study. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0).
Participants self-administered capsules of Northera (Droxidopa) by mouth twice daily for six weeks during this crossover study.
|
Placebo
n=3 Participants
This group includes all three participants who received placebo during the entire course of this crossover study. Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Participants self-administered capsules of placebo by mouth twice daily for six weeks during this crossover study.
|
|---|---|---|
|
Change From Baseline in Daily Bowel Movements
|
7 bowel movements per day
Standard Deviation 7 • Interval 0.83 to 1.06
|
8 bowel movements per day
Standard Deviation 8 • Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Change from baseline in standing time duration during each 6 week treatment arm (droxidopa and placebo).Change from baseline in Time standing duration
Outcome measures
| Measure |
Northera (Droxidopa)
n=3 Participants
This group includes all three participants who received Northera (Droxidopa) during the entire course of this crossover study. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0).
Participants self-administered capsules of Northera (Droxidopa) by mouth twice daily for six weeks during this crossover study.
|
Placebo
n=3 Participants
This group includes all three participants who received placebo during the entire course of this crossover study. Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Participants self-administered capsules of placebo by mouth twice daily for six weeks during this crossover study.
|
|---|---|---|
|
Change From Baseline in Time Standing Duration
|
300 Seconds
Standard Error 50
|
175 Seconds
Standard Error 25
|
SECONDARY outcome
Timeframe: Change from baseline in TUG test performance during each 6 week treatment arm (droxidopa and placebo)Change from baseline in Timed Up and Go (TUG) test performance
Outcome measures
| Measure |
Northera (Droxidopa)
n=3 Participants
This group includes all three participants who received Northera (Droxidopa) during the entire course of this crossover study. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0).
Participants self-administered capsules of Northera (Droxidopa) by mouth twice daily for six weeks during this crossover study.
|
Placebo
n=3 Participants
This group includes all three participants who received placebo during the entire course of this crossover study. Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Participants self-administered capsules of placebo by mouth twice daily for six weeks during this crossover study.
|
|---|---|---|
|
Change From Baseline in Timed Up and Go (TUG) Test Performance
|
10 seconds
Standard Error 2
|
9 seconds
Standard Error 1
|
SECONDARY outcome
Timeframe: Change from baseline in the 6MW distance during each 6 week treatment arm (droxidopa and placebo)Change from baseline in 6 minute walk test performance
Outcome measures
| Measure |
Northera (Droxidopa)
n=3 Participants
This group includes all three participants who received Northera (Droxidopa) during the entire course of this crossover study. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0).
Participants self-administered capsules of Northera (Droxidopa) by mouth twice daily for six weeks during this crossover study.
|
Placebo
n=3 Participants
This group includes all three participants who received placebo during the entire course of this crossover study. Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Participants self-administered capsules of placebo by mouth twice daily for six weeks during this crossover study.
|
|---|---|---|
|
Change From Baseline in 6 Minute Walk Test Performance
|
250 meters
Standard Error 75
|
200 meters
Standard Error 75
|
SECONDARY outcome
Timeframe: Change from baseline in OHSA score during each 6 week treatment arm (droxidopa and placebo)Change from baseline in scores on the Orthostatic Hypotension Symptom Assessment questionnaire. The scale rates the severity of OH symptoms from 0 to 10 ; with 10 defined as the worst possible.
Outcome measures
| Measure |
Northera (Droxidopa)
n=3 Participants
This group includes all three participants who received Northera (Droxidopa) during the entire course of this crossover study. The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant. Northera (droxidopa) was provided as gelatin capsules (sky blue and white, size 0).
Participants self-administered capsules of Northera (Droxidopa) by mouth twice daily for six weeks during this crossover study.
|
Placebo
n=3 Participants
This group includes all three participants who received placebo during the entire course of this crossover study. Placebo consists of empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from the Northera (droxidopa). Participants self-administered capsules of placebo by mouth twice daily for six weeks during this crossover study.
|
|---|---|---|
|
Change From Baseline in Scores on the Orthostatic Hypotension Symptom Assessment (OHSA) Questionnaire
|
-0.67 Scores on a scale
Interval -1.55 to 0.22
|
0 Scores on a scale
Interval 0.0 to 0.0
|
Adverse Events
Open Label: Northera (Droxidopa)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Crossover: Northera (Droxidopa)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Crossover: Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Open Label: Northera (Droxidopa)
n=3 participants at risk
The open label dose titration plan was initiated to determine each participant's maximally tolerated dose. Ascending doses of droxidopa of 100mg, 200mg, 300mg (maximum) were administered as tolerated based on the algorithm for determining droxidopa dose (see protocol). The droxidopa dose ascension was dependent on blood pressure less than 140mm Hg systolic and 90mm Hg diastolic and absence of symptoms of headache and/or nausea longer than two hours.
|
Crossover: Northera (Droxidopa)
n=3 participants at risk
This group includes adverse events from all three participants while on Northera (Droxidopa). The dosage for Northera (Droxidopa), 100mg, 200mg or 300mg, was based on the findings of the open label titration period and unique to each participant.
Participants self-administered capsules of Northera (Droxidopa) by mouth twice daily for six weeks.
|
Crossover: Placebo
n=3 participants at risk
This group includes adverse events from all three participants while on placebo.
Participants self-administered capsules of placebo by mouth twice daily for six weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
33.3%
1/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
66.7%
2/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
33.3%
1/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
66.7%
2/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
33.3%
1/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
|
Cardiac disorders
Elevated blood pressure
|
33.3%
1/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
66.7%
2/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
|
Renal and urinary disorders
potential Urinary Tract infection
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
33.3%
1/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
|
Nervous system disorders
Pre-syncopal episode while on baseline tilt table test
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
33.3%
1/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
|
Renal and urinary disorders
Minimally elevated creatinine level
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
33.3%
1/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
|
Renal and urinary disorders
Moderate Occult blood noted on urinalysis
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
33.3%
1/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
|
Nervous system disorders
Seizure
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
33.3%
1/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
0.00%
0/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
33.3%
1/3 • From enrollment up to 20 weeks
We identified a total of 16 non-serious adverse events among 3 subjects.
|
Additional Information
Stephen G. Kaler MD
Vagelos College of Physicians & Surgeons; Columbia University
Phone: 2123053669
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place