A Two Part Study (306A/306B) to Assess Droxidopa in Treatment of NOH in Patients With Parkinson's Disease
Condition: Orthostatic Hypotension; Parkinson's Disease
MeSH terms: Parkinson Disease; Hypotension, Orthostatic; Hypotension
Intervention: Droxidopa; Placebo
Intervention description: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment; Placebo
Intervention MeSH terms: Mannitol; Droxidopa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 225.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: lightheadedness; unsteadiness; dizziness; weak; fatigue; concentration; head & neck pain; standing/walking for a short time; standing/walking for a long time; Neurogenic Orthostatic Hypotension; falls; NOH; Parkinson's disease; weakness

Summary:

      This is a study to evaluate the effects of an investigational drug, Droxidopa, in
      participants with neurogenic orthostatic hypotension (NOH), associated with Parkinson's
      disease. Droxidopa is being studied to determine the effects on blood pressure changes upon
      standing up (orthostatic challenge). Symptoms and activity measurements, including patient
      reported falls, will be evaluated to determine the effectiveness of the study drug.

      Symptoms of NOH may include any of the following:

        -  Dizziness, light-headedness, feeling faint or feeling like you may blackout

        -  Problems with vision (blurring, seeing spots, tunnel vision, etc.)

        -  Weakness

        -  Fatigue

        -  Trouble concentrating

        -  Head & neck discomfort (the coat hanger syndrome)

        -  Difficulty standing for a short time or a long time

        -  Trouble walking for a short time or a long time

      The study duration is a maximum of approximately 14 weeks including up to 2 weeks for
      screening, up to 2 weeks for proper dose finding, followed by an 8 week treatment period and
      a follow-up visit after 2 weeks. A sufficient number of patients will be screened to allow
      approximately 211 randomized patients. An extension study is also available to continue
      treatment if determined appropriate by the study doctor. This Study is NCT01132326 sponsored
      by Chelsea Therapeutics and is enrolling by invitation only.
    

Eligibility criteria:

        Inclusion criteria:

          1. 18 years or over

          2. Clinical diagnosis of Parkinson's disease

          3. Clinical diagnosis of symptomatic neurogenic orthostatic hypotension

        At their baseline visit (Visit 2), patients must demonstrate:

          -  a score of at least 3 or greater on the OHQ composite

          -  a score of at least 3 or greater on the clinician CGI-S

          -  a fall of at least 20 mmHg in their systolic blood pressure, or 10 mmHg in their
             diastolic blood pressure, within 3 minutes of standing 4. Provide written informed
             consent to participate in the study and understand that they may withdraw their
             consent at any time without prejudice to their future medical care

        Exclusion Criteria:

          1. Score of 23 or lower on the mini-mental state examination (MMSE)

          2. Concomitant use of vasoconstricting agents for the purpose of increasing blood
             pressure;

             - Patients taking vasoconstricting agents such as ephedrine, dihydroergotamine, or
             midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is
             longer) prior to their baseline visit (Visit 2) and throughout the duration of the
             study

          3. Concomitant use of anti-hypertensive medication for the treatment of essential
             hypertension

          4. Have changed dose, frequency or type of prescribed medication, within two weeks of
             baseline visit (Visit 2) with the following exceptions:

               -  Vasoconstricting agents such a ephedrine, dihydroergotamine, or midodrine

               -  Short courses (less than 2 weeks) of medications or treatments that do not
                  interfere with, or exacerbate the patient's condition under study (e.g.
                  antibiotics)

          5. Known or suspected alcohol or substance abuse within the past 12 months (DSM-IV
             definition of alcohol or substance abuse)

          6. Women who are pregnant or breastfeeding

          7. Women of child bearing potential (WOCP) who are not using at least one method of
             contraception with their partner

          8. Male patients who are sexually active with a woman of child bearing potential (WOCP)
             and not using at least one method of contraception

          9. Untreated closed angle glaucoma, or treated closed angle glaucoma that, in the opinion
             of an ophthalmologist, might result in an increased risk to the patient

         10. Sustained severe hypertension (BP ≥ 180 mmHg systolic or ≥ 110 mmHg diastolic in the
             seated or supine position which is observed in 3 consecutive measurements over an
             hour)

         11. Any significant uncontrolled cardiac arrhythmia

         12. History of myocardial infarction, within the past 2 years

         13. Current unstable angina

         14. Congestive heart failure (NYHA Class 3 or 4)

         15. Diabetic autonomic neuropathy

         16. History of cancer within the past 2 years other than a successfully treated,
             non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in
             situ

         17. Gastrointestinal condition, which in the Investigator's judgment, may affect the
             absorption of study drug (e.g. ulcerative colitis, gastric bypass)

         18. Any major surgical procedure within 30 days of the baseline visit (Visit 2)

         19. Previously treated with droxidopa

         20. Currently receiving any investigational drug or have received an investigational drug
             within 30 days of the baseline visit (Visit 2)

         21. Any condition or laboratory test result, which in the Investigator's judgment, might
             result in an increased risk to the patient, or would affect their participation in the
             study. Additionally the Investigator has the ability to exclude a patient if for any
             reason they feel the subject is not a good candidate for the study or will not be able
             to follow study procedures.