Study to Assess the Clinical Benefit and Safety of Droxidopa in Parkinson's Disease

A Phase II, Double-Blind, Placebo-Controlled, Crossover Study to Assess Clinical Benefit and Safety of Droxidopa in the Treatment of Parkinson's Disease

Since droxidopa has been approved in Japan for treating freezing of gait in Parkinson's disease patients, this is to confirm and further investigate the safety and efficacy using a similar dose. The possible beneficial effects on cognition in mildly cognitively impaired Parkinson's disease patients will also be tested, since this problem in Parkinson's disease may be associated with decreased brain synthesis of norepinephrine (a neurotransmitter associated with multiple brain functions).

During this 11 week study, droxidopa will be slowly titrated up to 600 mg daily. Walking and freezing of gait will be evaluated and rated. Cognitive functions will be evaluated by a computer-based program.

Inclusion Criteria:

• Provide written informed consent to participate in the study

• Diagnosed with probable levodopa-responsive idiopathic PD (meeting United Kingdom PD Brain Bank diagnostic criteria), and receiving levodopa therapy for this disorder. Other PD medications can also be used.

• Must have AT LEAST ONE of below two criteria:

  1. At least 3 months incidence of typical freezing of gait symptoms, occurring while levodopa is otherwise providing an "on" mobility state (including at least one of the following Freezing of Gait patterns: start hesitancy, freezing at making turns or when passing through a doorway, spontaneous freezing during continued walking, or Freezing of Gait related to a simultaneous mental or physical activity) OR
  2. Have a screening score between 22 and 26 (inclusive) on the Montreal Cognitive Assessment

Exclusion Criteria:

• Taking direct acting vasoconstriction agent (i.e. ephedrine or midodrine). Subjects taking vasoconstrictor agents such as ephedrine or midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit
• Taking anti-hypertensive medication for the treatment of hypertension. Anti-hypertensive medication taken at night to prevent supine hypertension will be allowed
• Changing dose or frequency of PD medication within 2 weeks of baseline
• Use of cognitive-enhancing medications (donepezil, galantamine, rivastigmine, tacrine, or memantine), catechol-O-methyltransferase inhibitors (tolcapone or entacapone), anticholinergic drugs, or antipsychotic drugs (including quetiapine or clozapine).
• Known or suspected alcohol or substance abuse within 1 year (e.g. DSM-IV definition of alcoholism)
• Past or current history of chronic severe hypertension (with repeated findings of BP 150/90 mmHg in the supine or standing position)
• Symptomatic coronary artery disease, severe congestive heart failure (NYHA Class 3 or 4)
• Unable to remain off any effective Freezing of Gait medications for 12 hrs prior to Evaluation visits)
• Women who are pregnant, lactating, or plan to become pregnant during the course of this study
• Women of child bearing potential who are not using two methods of contraception (at least one barrier, i.e. condom) with their partner.
• Male subjects who are sexually active with a woman of child bearing potential and not using two methods of contraception (at least one barrier, for example, condom)
• A history of closed angle glaucoma;
• Active (in the last 6 months) atrial fibrillation or, in the investigator's opinion, any other significant cardiac arrhythmia that should preclude the subject from this trial
• History of myocardial infarction or unstable angina
• Congestive heart failure (NYHA Class 3 or 4)
• Diabetes insipidus, insulin-dependent diabetes mellitus, or diabetic neuropathy
• In the investigator's opinion, any other significant systemic illness
• Known or suspected malignancy (other than basal cell carcinoma)
• Known gastrointestinal illness or other gastrointestinal disorder that may, in the investigator's opinion, affect the absorption of study drug
• Any major surgical procedure within 30 days of the baseline visit
• Currently receiving any investigational drug or have received an investigational drug within 30 days of the baseline visit
• In the investigator's opinion, clinically significant abnormalities on clinical examination or laboratory testing that should preclude the subject from this trial.
• Findings from suicidality screening that are compatible with risk for suicide