Effect of L-Dihydroxyphenylserine (L-DOPS) on Falls in Patients With Neurogenic Orthostatic Hypotension (NOH)

Injuries associated with falls continue to pose a significant burden to patients with
Parkinson's disease (PD) both in terms of human suffering and economic losses. Overall annual
fall incidence rates range from 50-70% for PD patients, and recurrent falls are a major cause
of disability in PD. Approximately 20% of patients with Parkinson's disease develop NOH which
can lead to falls. Although the mechanisms underlying impaired postural stability and falls
are not well-known in patients with PD, attention is focused on the noradrenergic system.
L-DOPS, a drug that enhances norepinephrine levels in peripheral and central nervous system,
has been shown to moderate NOH, and often improve symptoms concomitant of PD and falls.

This study will help to determine the effect of L-DOPS in reducing falls and fall severity by
using an instrumented walkway to induce slip perturbations can assess the propensity for
falls and fall-related outcomes. It will assess fall events from the point of initiation
through recovery. The effect of L-DOPS on gait and balance parameters will also be measured
using force plate and inertial measurement unit (IMU) testing, and improvement in clinical
scores such as the MDS-UPDRS will be monitored.

Inclusion Criteria:

1. Subject has voluntarily signed and dated an informed consent form (ICF), approved by
an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), and provided
Health Insurance Portability and Accountability Act (HIPAA) (or other applicable
privacy regulation) authorization prior to any participation in the study.

2. Subject is male or female and is ≥ 30 and ≤ 83 years of age.

3. Parkinson's diagnosis with history of falls or gait difficulty.

4. Subject demonstrates neurogenic orthostatic hypotension (drop of 20 mm/Hg Systolic or
10 mm/Hg diastolic or both within 3 min of standing)

5. Fell more than once in past year.

6. Montreal Cognitive Assessment (MoCA) score ≥ 21.

7. Stable dose of levodopa, dopamine agonist, amantadine, and/or monoamine oxidase B
inhibitor, i.e. unchanged for 1 month.

8. Subject is ambulatory and able to walk ≥ 10 meters with/without the use of an
assistive device.

Exclusion Criteria:

1. Subject has a clinical diagnosis of an atypical Parkinsonism

2. Subject has a clinical diagnosis of PD that is suspicious to the investigator as being
a possible case of atypical Parkinson's

3. History of significant psychiatric illness such as schizophrenia or bipolar affective
disorder or any other significant psychiatric illness that in the opinion of the
investigator would interfere with participation in the study; history of major
depressive disorder in the past year, or current major depressive episode

4. Patients with systolic BP ≤70 mm/hg

5. Subjects with a history of coronary artery disease or congestive heart failure

6. Participation in another investigational drug or device study in during the 60 days
prior to the Screening Visit

7. Treatment with any anti-hypertensive medications

8. Treatment with any anti-spasmodic medications

9. Treatment with medications intended to elevate blood pressure

10. Treatment with non-specific monoamine oxidase (MAO) inhibitors