Open-Label Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)
Condition: Neurogenic Orthostatic Hypotension; Non-Diabetic Autonomic Neuropathy; Multiple System Atrophy; Dopamine Beta Hydroxylase Deficiency
MeSH terms: Multiple System Atrophy; Shy-Drager Syndrome; Hypotension, Orthostatic; Autonomic Nervous System Diseases; Hypotension; Atrophy
Intervention: Droxidopa; Placebo
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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 103.0
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 assess the durability of effect of Droxidopa 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:

          -  Participated in Droxidopa Protocol 302;

          -  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:

        Patients are not eligible for this study if they fulfill one or more of the following
        criteria:

          -  Currently taking ephedrine or midodrine;

          -  Patients taking ephedrine or midodrine must stop taking these drugs at least 2 days
             prior to their study entry visit (Visit 1).

          -  Currently taking anti-hypertensive medication;

             * 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;

               -  Reproductive potential:

               -  Female subjects should be either post-menopausal (amenorrhea for at least 12
                  consecutive months), surgically sterile, or women of child-bearing potential
                  (WOCP) who are using or agree to use acceptable methods of contraception.

               -  Acceptable contraceptives include intrauterine devices (IUDs), hormonal
                  contraceptives (oral, depot, patch or injectable) and double barrier methods such
                  as condoms or diaphragms with spermicidal gel or foam.

               -  For WOCP a urine pregnancy test must be conducted at each study visit.

               -  WOCP must be advised to use acceptable contraceptives throughout the study period
                  and for 30 days after the last dose of investigational product.

               -  If hormonal contraceptives are used they should be taken according to the package
                  insert.

               -  WOCP who are not currently sexually active must agree to use acceptable
                  contraception, as defined above, if they decide to become sexually active during
                  the period of the study and for 30 days after the last dose of investigational
                  product.

          -  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 umol/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.