A Clinical Study of Patients With Symptomatic NOH to Assess Sustained Effects of Droxidopa Therapy
Condition: Symptomatic Neurogenic Orthostatic Hypotension; Parkinson's Disease; Multiple Systems Atrophy; Pure Autonomic Failure; Dopamine Beta Hydroxylase Deficiency
MeSH terms: Parkinson Disease; Multiple System Atrophy; Shy-Drager Syndrome; Hypotension, Orthostatic; Pure Autonomic Failure; Hypotension
Intervention: Droxidopa; Placebo
Intervention description: Droxidopa at 100 mg, 200 mg, 300 mg; Placebo to match droxidopa capsules and strength designations
Intervention MeSH terms: Mannitol; Droxidopa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NOH; OH; PD; MSA; PAF; DBH

Summary:

      Evaluate the clinical efficacy and safety of droxidopa versus placebo over a 17 week
      (maximum) treatment period in patients with symptomatic NOH.
    

Eligibility criteria:

        Inclusion Criteria:

          -  1. 18 years and older and ambulatory (defined as able to walk at least 10 meters);

             2. Clinical diagnosis of symptomatic orthostatic hypotension associated with Primary
             Autonomic Failure (PD, MSA and PAF), Dopamine Beta Hydroxylase Deficiency;

             3. At the Baseline visit (Visit 2), patients must demonstrate:

               1. a score of at least 4 or greater on the Orthostatic Hypotension Symptom
                  Assessment (OHSA) Item #1;

               2. a fall of at least 20 mmHg in their systolic 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;

               1. 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. Known or suspected alcohol or substance abuse within the past 12 months
                  (DSM-IV definition of alcohol or substance abuse);

                  4. Women who are pregnant or breastfeeding;

                  5. Women of child bearing potential (WOCP) who are not using at least one method
                  of contraception with their partner;

                  6. Male patients who are sexually active with a woman of child bearing potential
                  (WOCP) and not using at least one method of contraception;

                  7. Untreated closed angle glaucoma;

                  8. Diagnosis of hypertension that requires treatment with antihypertensive
                  medications (short-acting antihypertensives to treat nocturnal supine HTN are
                  allowed in this study) Any significant uncontrolled cardiac arrhythmia;

                  9. History of myocardial infarction, within the past 2 years;

                  10. Current unstable angina;

                  11. Congestive heart failure (NYHA Class 3 or 4);

                  12. 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;

                  13. Gastrointestinal condition that may affect the absorption of study drug (e.g.
                  ulcerative colitis, gastric bypass);

                  14. Any major surgical procedure within 30 days prior to the Baseline visit
                  (Visit 2);

                  15. Previously treated with droxidopa within 30 days prior to the Baseline visit
                  (Visit 2);

                  16. Currently receiving any other investigational drug or have received an
                  investigational drug within 30 days prior to the Baseline visit (Visit 2);

                  17. 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;

                  18. 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.