Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension
Condition: Symptomatic Neurogenic Orthostatic Hypotension
MeSH terms: Hypotension, Orthostatic; Hypotension
Intervention: Droxidopa capsules; Placebo capsules
Intervention description: 100, 200 or 300 mg
Intervention MeSH terms: Droxidopa
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 453.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Parkinson's Disease; Multiple System Atrophy; Pure Autonomic Failure; Primary Autonomic Failure; Dopamine Beta Hydroxylase Deficiency

Summary:

      To evaluate the time to treatment intervention in patients with Parkinson's Disease (PD),
      Multiple System Atrophy (MSA), Pure Autonomic Failure (PAF), Non-Diabetic Autonomic
      Neuropathy (NDAN) or Dopamine Beta Hydroxylase (DBH) Deficiency who have been previously
      stabilized with droxidopa therapy for symptoms of neurogenic orthostatic hypotension (NOH)
      (dizziness, light-headedness, or feelings that they are about to black out)
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years or older and able to stand (with or without limited assistance)

          -  Clinical diagnosis of symptomatic orthostatic hypotension associated with Primary
             Autonomic Failure (PD, MSA or PAF) or NDAN or DBH Deficiency

          -  Score of at least 4 or greater on Orthostatic Hypotension Symptom Assessment (OHSA)
             Item #1 (measured at Screening [Visit 1] and the first Titration Visit [Visit 2a]
             prior to dosing)

          -  A documented drop of at least 20 millimeters of mercury (mmHg) in SBP, within 3
             minutes of standing. This can either be documented in the patient history or assessed
             during Screening prior to the first Titration Visit (Visit 2a)

          -  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

        Additional inclusion criteria for patients taking prescribed droxidopa prior to study
        entry:

        Patients who are taking prescribed droxidopa therapy are eligible to participate in the
        study if they meet the other inclusion criteria and also have been on a stable dose of
        prescribed droxidopa for at least 2 weeks prior to the Screening Visit (Visit 1). In
        addition, they must meet either of the following at the Screening Visit (Visit 1):

          -  The patient's Visit 1 OHSA Item #1 score is ≥ 7 AND the prescribed dose is ≤ 300 mg
             three times daily (TID); OR

          -  The patient's Visit 1 OHSA Item #1 score is ≤6 AND worsens by ≥ 2 units when retested
             after washing out of droxidopa for at least 3 days

        Exclusion Criteria:

          -  In the investigator's opinion, the patient is not able to understand or cooperate with
             study procedures

          -  Known or suspected alcohol or substance use disorder within the past 12 months (DSM-5
             criteria)

          -  Women who are pregnant or breastfeeding

          -  Women of childbearing potential (WOCP) who are not using at least one method of
             contraception with their partner

          -  Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg
             diastolic. Sustained is defined as the average of 3 observations each at least 10
             minutes apart with the patient having been supine and at rest for at least 5 minutes
             prior to each measurement.

          -  Untreated closed angle glaucoma

          -  Diagnosis of hypertension that requires treatment with antihypertensive medications
             (short-acting antihypertensives to treat nocturnal supine hypertension are allowed in
             this study)

          -  Any significant uncontrolled cardiac arrhythmia

          -  History of myocardial infarction or stroke, within the past 2 years

          -  Current unstable angina

          -  Congestive heart failure (NYHA Class 3 or 4)

          -  Diabetic autonomic neuropathy

          -  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

          -  Any major surgical procedure within the past 30 days

          -  Currently receiving any investigational drug or have received an investigational drug
             within the past 28 days

        Additional protocol defined exclusion criteria do apply