Trial Outcomes & Findings for Study to Assess the Benefit of Midodrine in the Treatment of Patients With Neurogenic Orthostatic Hypotension (NCT NCT00555880)
NCT ID: NCT00555880
Last Updated: 2021-06-14
Results Overview
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
COMPLETED
PHASE4
24 participants
1 hour post-dose
2021-06-14
Participant Flow
Participant milestones
| Measure |
Midodrine/Placebo
Participants received a single oral dose of Midodrine hydrochloride (HCl) followed by matching Placebo the next day
|
Placebo/Midodrine
Participants received Placebo followed by a single oral dose of Midodrine HCl the next day
|
|---|---|---|
|
Treatment Period 1 (1 Day)
STARTED
|
13
|
11
|
|
Treatment Period 1 (1 Day)
COMPLETED
|
13
|
11
|
|
Treatment Period 1 (1 Day)
NOT COMPLETED
|
0
|
0
|
|
Washout (1 Day)
STARTED
|
13
|
11
|
|
Washout (1 Day)
COMPLETED
|
13
|
11
|
|
Washout (1 Day)
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2 (1 Day)
STARTED
|
13
|
11
|
|
Treatment Period 2 (1 Day)
COMPLETED
|
13
|
11
|
|
Treatment Period 2 (1 Day)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Assess the Benefit of Midodrine in the Treatment of Patients With Neurogenic Orthostatic Hypotension
Baseline characteristics by cohort
| Measure |
Midodrine/Placebo
n=13 Participants
Participants received a single oral dose of Midodrine HCl followed by matching Placebo the next day
|
Placebo/Midodrine
n=11 Participants
Participants received matching Placebo followed by a single oral dose of Midodrine HCl the next day
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.4 years
STANDARD_DEVIATION 17.84 • n=5 Participants
|
60.8 years
STANDARD_DEVIATION 12.91 • n=7 Participants
|
60.0 years
STANDARD_DEVIATION 15.46 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 hour post-dosePopulation: The Full Analysis Set (FAS), defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing
|
551.3 seconds
Standard Deviation 115.63
|
461.0 seconds
Standard Deviation 190.74
|
PRIMARY outcome
Timeframe: 1 hour post-dosePopulation: The FAS, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near- syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. In this outcome measure, the data analyzed are the same as for Outcome Measure 1 but the summary data are presented as least squares mean (standard error).
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing Analysis #2
|
552.4 seconds
Standard Error 32.93
|
460.0 seconds
Standard Error 32.93
|
PRIMARY outcome
Timeframe: 1 hour post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. The Koch procedure is a 3-step process to analyze results while utilizing the available information on magnitude of differences.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing-Re-analysis With The Koch Procedure
|
551.3 seconds
Standard Deviation 115.63
|
461.0 seconds
Standard Deviation 190.74
|
SECONDARY outcome
Timeframe: 1 hour post-dosePopulation: The Per-protocol set, defined as participants in the Full Analysis Set who completed the study and were protocol compliant.
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=21 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=21 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Time to Onset of Near-syncopal Symptoms in The Per-protocol Population
|
544.3 seconds
Standard Deviation 122.34
|
447.9 seconds
Standard Deviation 199.31
|
SECONDARY outcome
Timeframe: 1 hour post-dosePopulation: The Per-protocol set, defined as participants in the Full Analysis Set who completed the study and were protocol compliant.
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near- syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. In this outcome measure, the data analyzed are the same as for Outcome Measure 4 but the summary data are presented as least squares mean (standard error).
Outcome measures
| Measure |
Midodrine HCl
n=21 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=21 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Time to Onset of Near-syncopal Symptoms in The Per-protocol Population Analysis #2
|
545.1 seconds
Standard Error 36.90
|
447.2 seconds
Standard Error 36.90
|
SECONDARY outcome
Timeframe: 1 hour post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=13 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=11 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Time to Near-syncopal Symptoms at Treatment Visit 1
|
539.5 seconds
Standard Error 45.91
|
448.4 seconds
Standard Error 49.91
|
SECONDARY outcome
Timeframe: 1 and 3 hours post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
Duration of effect was defined as the difference in time to onset of near-syncopal symptoms between the first and second tilt table test, conducted at 1 hour and 3 hours post-dose, respectively, at Treatment Visit 2 (time to onset at 3 hours minus time at 1 hour). The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=11 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=13 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Duration of The Effect of Treatment at 3 Hours Post-dose
|
45.1 seconds
Standard Deviation 94.03
|
48.0 seconds
Standard Deviation 114.96
|
SECONDARY outcome
Timeframe: Approximately 1 hour post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
The OHSA measures the severity of six symptoms/symptom complexes associated with orthostatic hypotension. Subjects rated symptoms experienced during the tilt table test on an eleven-point scale from "none" to "worst possible". The OHSA total score is the sum of six subscales, ranging from 0 (no symptoms) to 60 (worst possible symptoms). The OHSA was completed after the tilt table test was over, but was answered with reference to symptoms experienced during testing. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Total Score of the Orthostatic Hypotension Symptom Assessment (OHSA)
|
13.7 scores on a scale
Standard Error 2.95
|
19.4 scores on a scale
Standard Error 2.95
|
SECONDARY outcome
Timeframe: Approximately 1 hour post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
The OHSA measures the severity of six symptoms/symptom complexes associated with OH: dizziness, lightheadedness, and feeling faint; problems with vision; weakness; fatigue; trouble concentrating; and head/neck discomfort. Subjects rated symptoms experienced during the tilt table test on an eleven-point scale from "none" to "worst possible". Scores for each subscale range from 0 (no symptoms) to 10 (worst possible symptoms). The OHSA was completed after the tilt table test was over, but was answered with reference to symptoms experienced during testing. The tilt table test is a 10-minute assessment performed using a tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured with straps to prevent injury. After an equilibration period with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, and feeling faint.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Scores for 6 Items of The OHSA
Dizziness, Lightheadedness, and Feeling Faint
|
3.4 scores on a scale
Standard Deviation 3.44
|
4.7 scores on a scale
Standard Deviation 3.57
|
|
Scores for 6 Items of The OHSA
Problems with Vision
|
1.5 scores on a scale
Standard Deviation 2.32
|
2.7 scores on a scale
Standard Deviation 3.43
|
|
Scores for 6 Items of The OHSA
Weakness
|
3.0 scores on a scale
Standard Deviation 3.13
|
4.1 scores on a scale
Standard Deviation 3.17
|
|
Scores for 6 Items of The OHSA
Fatigue
|
2.7 scores on a scale
Standard Deviation 3.22
|
3.5 scores on a scale
Standard Deviation 3.48
|
|
Scores for 6 Items of The OHSA
Trouble Concentrating
|
1.7 scores on a scale
Standard Deviation 2.04
|
2.6 scores on a scale
Standard Deviation 3.13
|
|
Scores for 6 Items of The OHSA
Head/Neck Discomfort
|
1.9 scores on a scale
Standard Deviation 2.52
|
2.1 scores on a scale
Standard Deviation 3.21
|
SECONDARY outcome
Timeframe: 1 and 3 hours post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
The CGI-I instrument assesses the overall impression of the subject's orthostatic hypotension during the tilt table test by using a 7-point scale, with 1 being Very much improved; 2, Much improved; 3, Slightly improved; 4, No change; 5, Slightly worse; 6, Much worse; and 7, Very much worse. The clinician completed the CGI-I after each of the tilt table tests. A patient was assessed as "Improved" if the score was 1, 2, or 3. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Number of Participants With Improvement of Clinician Clinician's Global Impression- Improvement (CGI-I) Scores After Tilt Table Test
Treatment Visit 1- 1 hour post-dose, n=13, 11
|
4 participants
|
4 participants
|
|
Number of Participants With Improvement of Clinician Clinician's Global Impression- Improvement (CGI-I) Scores After Tilt Table Test
Treatment Visit 2- 1 hour post-dose, n=11, 13
|
6 participants
|
4 participants
|
|
Number of Participants With Improvement of Clinician Clinician's Global Impression- Improvement (CGI-I) Scores After Tilt Table Test
Treatment Visit 2- 3 hour post-dose, n= 11, 12
|
3 participants
|
5 participants
|
SECONDARY outcome
Timeframe: 1 and 3 hours post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
The CGI-I instrument assesses the overall impression of the subject's orthostatic hypotension during the tilt table test by using a 7-point scale, with 1 being Very much improved; 2, Much improved; 3, Slightly improved; 4, No change; 5, Slightly worse; 6, Much worse; and 7, Very much worse. The patient completed the CGI-I after each of the tilt table tests. A patient was assessed as "Improved" if the score was 1, 2, or 3. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Number of Participants With Improvement of Patient CGI-I Scores After Tilt Table Test
Treatment Visit 1-1 hour post-dose, n= 13, 11
|
3 participants
|
2 participants
|
|
Number of Participants With Improvement of Patient CGI-I Scores After Tilt Table Test
Treatment Visit 2-1 hour post-dose, n= 11, 13
|
5 participants
|
3 participants
|
|
Number of Participants With Improvement of Patient CGI-I Scores After Tilt Table Test
Treatment Visit 2-3 hour post-dose, n= 11, 12
|
3 participants
|
3 participants
|
SECONDARY outcome
Timeframe: 1 hour post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
Blood pressure was recorded just before tilt table testing and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Final Blood Pressure During Tilt Table Testing
Systolic Pressure
|
106.5 mmHg
Standard Deviation 37.27
|
90.2 mmHg
Standard Deviation 24.17
|
|
Final Blood Pressure During Tilt Table Testing
Diastolic Pressure
|
70.6 mmHg
Standard Deviation 16.44
|
60.6 mmHg
Standard Deviation 15.04
|
SECONDARY outcome
Timeframe: 1 and 3 hours post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
Blood pressure was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Systolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 1 minute 1 hour post-dose, n= 11, 13
|
142.2 mmHg
Standard Deviation 44.20
|
97.3 mmHg
Standard Deviation 24.55
|
|
Systolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 1 minute 3 hours post-dose, n= 11, 12
|
110.1 mmHg
Standard Deviation 19.06
|
94.9 mmHg
Standard Deviation 31.36
|
|
Systolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 10 minutes 1 hour post-dose, n= 10, 8
|
121.7 mmHg
Standard Deviation 37.57
|
102.9 mmHg
Standard Deviation 21.03
|
|
Systolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 10 minutes 3 hours post-dose, n= 7, 6
|
108.3 mmHg
Standard Deviation 30.48
|
107.2 mmHg
Standard Deviation 19.32
|
SECONDARY outcome
Timeframe: 1 and 3 hours post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
Blood pressure was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Diastolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 1 minute 1 hour post-dose, n= 11, 12
|
81.5 mmHg
Standard Deviation 19.09
|
60.8 mmHg
Standard Deviation 13.99
|
|
Diastolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 10 minutes 1 hour post-dose, n= 10, 8
|
79.6 mmHg
Standard Deviation 16.18
|
64.9 mmHg
Standard Deviation 11.22
|
|
Diastolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 1 minute 3 hours post-dose, n= 11, 12
|
66.1 mmHg
Standard Deviation 9.66
|
60.3 mmHg
Standard Deviation 18.53
|
|
Diastolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 10 minutes 3 hours post-dose, n= 7, 6
|
69.3 mmHg
Standard Deviation 13.55
|
60.7 mmHg
Standard Deviation 14.69
|
SECONDARY outcome
Timeframe: 1 and 3 hours post-dosePopulation: The Full Analysis Set, defined as subjects who were randomized, received at least one dose of study drug, and had at least one measurement of time to syncope during tilt table testing.
Heart rate was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
n=24 Participants
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Heart Rate at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 1 minute 1 hour post-dose, n= 11, 13
|
77.6 beats per minute
Standard Deviation 13.93
|
80.5 beats per minute
Standard Deviation 14.07
|
|
Heart Rate at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 10 minutes 1 hour post-dose, n= 10, 8
|
77.7 beats per minute
Standard Deviation 16.08
|
79.5 beats per minute
Standard Deviation 16.48
|
|
Heart Rate at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 1 minute 3 hours post-dose, n= 11, 12
|
79.7 beats per minute
Standard Deviation 11.30
|
80.9 beats per minute
Standard Deviation 13.19
|
|
Heart Rate at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2
At 10 minutes 3 hours post-dose, n= 8, 6
|
80.9 beats per minute
Standard Deviation 11.66
|
81.3 beats per minute
Standard Deviation 20.16
|
SECONDARY outcome
Timeframe: Baseline to dischargePopulation: The Safety population, defined as all subjects who received at least one dose of investigational product.
For hematology, blood samples (5.0mL) were taken at screening, study admission (if greater than 14 days since screening) and discharge/early termination. The following parameters were assessed: hemoglobin, hematocrit, red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count - total and differential (WBC), and platelet count. A shift in reference to normal was either lower or higher at discharge.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
Hemoglobin
|
1 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
Hematocrit
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
RBC
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
MCV
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
MCH
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
MCHC
|
2 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
WBC
|
1 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge
Platelet count
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline to dischargePopulation: The Safety population, defined as all subjects who received at least one dose of investigational product.
For biochemistry, blood samples (10.0mL) were taken at screening, admission (if greater than 14 days since screening) and discharge/early termination. The following parameters were assessed: sodium, potassium, calcium, blood urea nitrogen (BUN)/Urea, creatinine, albumin, total protein and albumin/globulin (A/G) ratio, globulin, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin, glucose, chloride, and creatine kinase. A shift in reference to normal was either lower or higher at discharge.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
AST
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Sodium
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Potassium
|
2 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Calcium
|
1 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
BUN/Urea
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Creatinine
|
1 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Albumin
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Total protein and A/G ratio
|
2 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Globulin
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
ALT
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
ALP
|
1 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
GGT
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Total bilirubin
|
1 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Glucose
|
6 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Chloride
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge
Creatine kinase
|
1 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline to dischargePopulation: The Safety population, defined as all subjects who received at least one dose of investigational product.
For urinalysis, samples were taken at screening, study admission (if greater than 14 days since screening) and discharge/early termination): glucose, blood, protein, pH, specific gravity, leukocyte esterase, and microscopic examination. A shift in reference to normal was higher at discharge.
Outcome measures
| Measure |
Midodrine HCl
n=24 Participants
Midodrine HCl: one dose, 10-30mg, given orally
|
Placebo
Placebo: A daily dose of Placebo tablets matching Midodrine HCl in appearance and number
|
|---|---|---|
|
Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
Glucose
|
1 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
Blood
|
2 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
Protein
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
pH
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
Specific gravity
|
0 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
Leukocyte esterase
|
2 participants
|
—
|
|
Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge
Microscopic examination
|
0 participants
|
—
|
Adverse Events
Midodrine/Placebo
Placebo/Midodrine
Serious adverse events
| Measure |
Midodrine/Placebo
n=13 participants at risk
Participants received a single oral dose of Midodrine HCl (10-30mg) followed by placebo the next day.
|
Placebo/Midodrine
n=11 participants at risk
Participants received Placebo followed by a single oral dose of Midodrine HCl (10-30mg) the next day.
|
|---|---|---|
|
Nervous system disorders
Multiple sclerosis aggravated
|
7.7%
1/13
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
0.00%
0/11
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
Other adverse events
| Measure |
Midodrine/Placebo
n=13 participants at risk
Participants received a single oral dose of Midodrine HCl (10-30mg) followed by placebo the next day.
|
Placebo/Midodrine
n=11 participants at risk
Participants received Placebo followed by a single oral dose of Midodrine HCl (10-30mg) the next day.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
7.7%
1/13
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
0.00%
0/11
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
|
Cardiac disorders
Atrioventricular block first degree
|
7.7%
1/13
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
0.00%
0/11
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
|
Gastrointestinal disorders
Vomiting NOS
|
7.7%
1/13
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
0.00%
0/11
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
7.7%
1/13
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
0.00%
0/11
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
|
Nervous system disorders
Dizziness
|
7.7%
1/13
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
0.00%
0/11
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
|
Nervous system disorders
Headache NOS
|
7.7%
1/13
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
0.00%
0/11
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
|
Vascular disorders
Hypertension aggravated
|
0.00%
0/13
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
18.2%
2/11
Adverse events are reported by randomized arm and not by actual treatment intervention received.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER