A Clinical Study for Patients With Neurogenic Orthostatic Hypotension (NOH) Using Droxidopa
Condition: Symptomatic Neurogenic Orthostatic Hypotension (NOH); Non-diabetic Neuropathy; Primary Autonomic Failure; Dopamine Beta Hydroxylase Deficiency
MeSH terms: Hypotension, Orthostatic; Pure Autonomic Failure; Autonomic Nervous System Diseases; Hypotension
Intervention: Placebo; Droxidopa
Intervention description: 100 mg, oral, three times per day 200 mg, oral, three times per day 300 mg, oral, three times per day 400 mg, oral, three times per day 500 mg, oral, three times per day 600 mg, oral, three times per day; 100 mg, oral, three times per day 200 mg, oral, three times per day 300 mg, oral, three times per day 400 mg, oral, three times per day 500 mg, oral, three times per day 600 mg, oral, three times per day
Intervention MeSH terms: Droxidopa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 263.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NOH; Neurogenic Orthostatic Hypotension; Orthostatic hypotension; PAF; Pure Autonomic Failure; MSA; Multiple System Atrophy; Neuropathy; Autonomic Failure; Parkinson; Dopamine Deficiency; Dopamine; Droxidopa

Summary:

      The purpose of this study is to see whether droxidopa is effective in treating symptoms of
      neurogenic orthostatic hypotension in patients with Primary Autonomic Failure (Pure Autonomic
      Failure, Multiple System Atrophy, Parkinson's Disease), Non-diabetic neuropathy, or Beta
      Hydroxylase deficiency.
    

Eligibility criteria:

        Inclusion Criteria:

        To be eligible for inclusion, each patient must fulfill the following criteria:

          -  Male or female and aged 18 years or over

          -  Clinical diagnosis of orthostatic hypotension associated with Primary Autonomic
             Failure (PD, MSA and PAF), Dopamine Beta Hydroxylase Deficiency or Non-Diabetic
             Autonomic Neuropathies

          -  A documented fall in systolic blood pressure of at least 20 mmHg, or in diastolic
             blood pressure of at least 10 mmHg, within 3 minutes after standing;

          -  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:

          -  Currently taking ephedrine or midodrine

          -  Patients taking ephedrine or midodrine must stop taking these drugs at least 2 days
             prior to their baseline visit (Visit 2).

          -  The use of short-acting anti-hypertensive medications at bedtime is permitted.

          -  Currently taking tri-cyclic antidepressant medication or other norepinephrine
             re-uptake inhibitors;

          -  Have changed dose, frequency and or type of prescribed medication, within two weeks of
             study start (excluding ephedrine and midodrine)

          -  History of more than moderate alcohol consumption

          -  History of known or suspected drug or substance abuse

          -  Women of childbearing potential who are not using a medically accepted contraception

          -  For WOCP a serum beta HCG pregnancy test must be conducted at screening, and a urine
             pregnancy test must be conducted at baseline and study termination; the results must
             be negative at screening and at baseline for the patient to receive study medication.

          -  Sexually active males whose partner is a WOCP and who do not agree to use condoms for
             the duration of the study and for 30 days after the last dose;

          -  Women who are pregnant or breast feeding

          -  Known or suspected hypersensitivity to the study medication or any of its ingredients

          -  Pre-existing sustained severe hypertension (BP 180/110 mmHg in the sitting position)

          -  Have atrial fibrillation or, in the investigator's opinion, have any other significant
             cardiac arrhythmia

          -  Any other significant systemic, hepatic, cardiac or renal illness

          -  Diabetes mellitus or insipidus

          -  Have a history of closed angle glaucoma

          -  Have a known or suspected malignancy

          -  Have a serum creatinine level > 130 mmol/L

          -  Patients with known gastrointestinal illness or other gastrointestinal disorder that
             may, in the investigator's opinion, affect the absorption of study drug

          -  In the investigator's opinion, have clinically significant abnormalities on clinical
             examination or laboratory testing

          -  In the investigator's opinion, are unable to adequately co-operate because of
             individual or family situation

          -  In the investigator's opinion, are suffering from a mental disorder that interferes
             with the diagnosis and/or with the conduct of the study, e.g. schizophrenia, major
             depression, dementia

          -  Are not able or willing to comply with the study requirements for the duration of the
             study

          -  Have participated in another clinical trial with an investigational agent (including
             named patient or compassionate use protocol) within 4 weeks before the start of the
             study

          -  Previous enrolment in the study.