Tilt-Table Study of the Clinical Efficacy of Midodrine in Symptomatic Orthostatic Hypotension

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01518946
• Collaborator: (none)
• Enrollment: 24
• Locations: 13
• Arms: 2
• Actual Duration (Months): 13.3
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether midodrine works against the symptoms of orthostatic hypotension caused by being on a tilt table.

Condition or Disease	Intervention/Treatment	Phase
Orthostatic Hypotension	Drug: Midodrine HCl; Drug: Placebo	Phase 4

Detailed Description

The efficacy of midodrine will be assessed in those subjects who have severe symptoms of orthostatic hypotension when not taking midodrine and are controlled when taking midodrine. The study will involve approximately 4 overnight stays.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 4, Randomized, Double-blind, Placebo-controlled, Crossover Study to Investigate the Clinical Benefit of Midodrine Hydrochloride in Male and Female Subjects With Symptomatic Orthostatic Hypotension
• Actual Study Start Date: May 14, 2012
• Actual Primary Completion Date: Jun 22, 2013
• Actual Study Completion Date: Jun 22, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Midodrine HCl	Drug: Midodrine HCl; dose at the subject's current dose level; Other Names: ProAmatine®
Placebo Comparator: Placebo	Drug: Placebo; single dose of matching placebo

Outcome Measures

Primary Outcome Measures

1. Time to Onset of Syncope/Near Syncope While on Tilt Table [1 hour post-dose]

   After a 30-minute supine period, the table was tilted from 0-90º within 30 seconds and maintained in that position for 45 minutes or until endpoint. Subjects were monitored for near-syncopal symptoms (subject felt sufficiently dizzy, lightheaded, faint, or felt like they were about to black out and requested the table to be returned to horizontal). Such a report ended the test. Alternatively, if the investigator observed that the subject was about to lose consciousness, that also constituted an endpoint.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male and female subjects must be 18 years of age or older and ambulatory.

2. Females of child-bearing potential (FOCP) must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test.

3. A documented history of severe Symptomatic Orthostatic Hypotension (SOH) that, in the judgment of the treating physician, has required treatment with midodrine HCl , and has been at a stable dose for at least 3 months.

4. The subject has manifested at least 1 of the following symptoms while standing or had a medical history of 1 of the following when not treated for orthostatic hypotension (OH): dizziness, lightheadedness, feeling faint, or feeling like they might black out.

Exclusion Criteria:

1. The subject is a pregnant or lactating female.

2. The subject has pre-existing sustained supine hypertension greater than 180mmHg systolic and 110mmHg diastolic BP or had these measurements at the Screening Visit. Sustained is defined as persistently greater at 2 separate measurements at least 5 minutes apart with the subject supine and at rest for the 5 minutes.

3. Subjects taking concomitant medications of interest are excluded unless those medications are reviewed and discussed with the Medical Monitor or Study Physician and documented prior to enrolling the subject. If agreement is reached between the Investigator and Sponsor for the subject to continue in the study, all allowed medications should be maintained at a constant dose throughout the study.

4. The Principal Investigator deems any clinical laboratory test (at the Screening Visit) abnormality to be clinically significant

5. The subject has participated in other studies of investigational drugs or devices within 30 days prior to enrollment in this study (other than Study SPD426-406).

6. Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the investigational product or study procedures.

7. The subject has a concurrent chronic or acute illness, disability, or other condition (including significant unexpected laboratory or electrocardiogram [ECG] findings) that might confound the results of the tests and/or measurements administered in this study, or that might have increased the risk to the subject.

8. Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.

9. Prior enrollment failure or randomization in this study.

10. History of alcohol abuse or other substance abuse within the last year.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida	United States	33486
2	Advance Research Institute Inc	New Port Richey	Florida	United States	34653
3	Analab Clinical Research Inc	Lenexa	Kansas	United States	66219
4	Mayo Clinic	Rochester	Minnesota	United States	55905
5	Buffalo Clinical Research Center (BCRC)	Buffalo	New York	United States	14202
6	NYU Medical Centre	New York	New York	United States	10016
7	Columbia University	New York	New York	United States	10032
8	Cleveland Clinic	Cleveland	Ohio	United States	44195
9	Kidney and Hypertension Center	Roseburg	Oregon	United States	97471
10	New Orleans Center for Clinical Research - Knoxville	Knoxville	Tennessee	United States	37920
11	The Heartbeat Clinic, PA	McKinney	Texas	United States	75069
12	Aspen Clinical Research	Orem	Utah	United States	84058
13	Aurora Cardiovascular Services	Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01518946
• Other Study ID Numbers: SPD426-406
• First Posted: Jan 26, 2012
• Last Update Posted: Jun 8, 2021
• Last Verified: May 1, 2021

• Keywords provided by Shire: Symptomatic Orthostatic Hypotension
• Additional relevant MeSH terms: Hypotension, Orthostatic; Hypotension; Midodrine

Study Results

Participant Flow

Arm/Group Title	Midodrine HCl (Open-label Phase)	Placebo First, Then Midodrine HCl (Randomized Phase)	Midodrine HCl First, Then Placebo (Randomized Phase)
Arm/Group Description	On the morning of Day -1, subjects took their usual morning dose of midodrine HCl, using their own midodrine HCl supplies at approximately the same time before rising that they would normally take their morning dose. On the morning of Day 1, subjects had their usual morning dose of midodrine HCl withheld.	Placebo for first intervention on Day 2, then Midodrine hydrochloride dose at the subject's current dose level for the second intervention on Day 3.	Midodrine hydrochloride dose at the subject's current dose level for the first intervention Day 2, then placebo for second intervention on Day 3.
Period Title: Open-label Phase
STARTED	24	0	0
COMPLETED	20	0	0
NOT COMPLETED	4	0	0
Period Title: Open-label Phase
STARTED	0	10	10
COMPLETED	0	9	10
NOT COMPLETED	0	1	0
Period Title: Open-label Phase
STARTED	0	9	10
COMPLETED	0	9	10
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo First, Then Midodrine HCl (Randomized Phase)	Midodrine HCl First, Then Placebo (Randomized Phase)	Total
Arm/Group Description	Placebo for first intervention on Day 2, then Midodrine hydrochloride dose at the subject's current dose level for the second intervention on Day 3.	Midodrine hydrochloride dose at the subject's current dose level for the first intervention Day 2, then placebo for second intervention on Day 3.	Total of all reporting groups
Overall Participants	10	10	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.0 (19.52)	42.1 (18.64)	45.1 (18.82)
Age, Customized (Count of Participants)
18 to 65 years, inclusive	8 80%	8 80%	16 80%
>= 66 years	2 20%	2 20%	4 20%
Sex: Female, Male (Count of Participants)
Female	8 80%	10 100%	18 90%
Male	2 20%	0 0%	2 10%
Region of Enrollment (Count of Participants)
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Time to Onset of Syncope/Near Syncope While on Tilt Table
Description	After a 30-minute supine period, the table was tilted from 0-90º within 30 seconds and maintained in that position for 45 minutes or until endpoint. Subjects were monitored for near-syncopal symptoms (subject felt sufficiently dizzy, lightheaded, faint, or felt like they were about to black out and requested the table to be returned to horizontal). Such a report ended the test. Alternatively, if the investigator observed that the subject was about to lose consciousness, that also constituted an endpoint.
Time Frame	1 hour post-dose

Outcome Measure Data

Analysis Population Description

The Full Analysis Set was defined as all randomized subjects who received at least 1 dose of randomized investigational product and who had at least 1 measurement of the time to onset of syncopal symptoms/near syncope during tilt-table testing.

Arm/Group Title	Placebo	Midodrine HCl
Arm/Group Description	single dose of matching placebo	dose at the subject's current dose level
Measure Participants	19	19
Least Squares Mean (Standard Error) [seconds]	1105.6 (186.82)	1626.6 (186.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Midodrine HCl
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0131
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	521.0
	Confidence Interval	(2-Sided) 95%; 124.2 to 917.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Midodrine HCl (Open-label Phase)		Placebo (Randomized Phase)		Midodrine HCl (Randomized Phase)
Arm/Group Description	dose at the subject's current dose level		single dose of matching placebo		dose at the subject's current dose level
All Cause Mortality
	Midodrine HCl (Open-label Phase)		Placebo (Randomized Phase)		Midodrine HCl (Randomized Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Midodrine HCl (Open-label Phase)		Placebo (Randomized Phase)		Midodrine HCl (Randomized Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Midodrine HCl (Open-label Phase)		Placebo (Randomized Phase)		Midodrine HCl (Randomized Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/24 (12.5%)		1/20 (5%)		1/20 (5%)
Gastrointestinal disorders
Nausea	2/24 (8.3%)	2	0/20 (0%)	0	0/20 (0%)	0
General disorders
Fatigue	0/24 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Back Pain	0/24 (0%)	0	1/20 (5%)	1	0/20 (0%)	0
Nervous system disorders
Headache	2/24 (8.3%)	2	0/20 (0%)	0	0/20 (0%)	0
Vascular disorders
Flushing	0/24 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Hot Flush	0/24 (0%)	0	0/20 (0%)	0	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.