Clinical Efficacy of Midodrine in Symptomatic Orthostatic Hypotension

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 9 overnight stays.

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.