Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH) (Droxi-304)
Condition: Primary Autonomic Failure; Dopamine Beta Hydroxylase Deficiency; Non-Diabetic Neuropathy; Neurogenic Orthostatic Hypotension
MeSH terms: Hypotension, Orthostatic; Pure Autonomic Failure; Autonomic Nervous System Diseases; Hypotension
Intervention: Droxidopa
Intervention description: Oral, 100, 200, 300, 400, 500, 600 mg TID, 12 months
Intervention MeSH terms: Droxidopa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 350.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Symptomatic NOH

Summary:

      Symptomatic NOH in patients with primary autonomic failure is thought to be a consequence of
      norepinephrine depletion leading to a diminished capacity to effect an appropriate
      cardiovascular response to an orthostatic challenge resulting in symptomatic
      cerebral-hypoperfusion. Droxidopa augments norepinephrine levels which should lead to
      improved cerebral perfusion following orthostatic challenge thereby reducing the symptoms of
      NOH. The present study will evaluate the long-term safety of droxidopa.
    

Eligibility criteria:

        Inclusion Criteria:

        To be eligible for inclusion, each patient must fulfill the following criteria:

          -  Demonstrated a symptomatic response (an improvement of at least 1 point in Item #1 of
             the OHSA) to treatment with droxidopa during open-label titration in Droxidopa
             Protocol 301 ;

          -  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 vasoconstricting agents such as ephedrine, dihydroergotamine, or
             midodrine; 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 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
             starting droxidopa treatment within Protocol 304, with the following exceptions:

               -  vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine (see
                  exclusion a),

               -  short courses of antibiotics or other medications/treatments that do not
                  interfere with, or exacerbate the patient's condition under study.

          -  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
                  (amenorrhoea 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 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. 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 greater than or equal to 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;

          -  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 other than
             droxidopa (including named patient or compassionate use protocol) within 4 weeks
             before starting droxidopa treatment within Protocol 304;

          -  Previous enrolment in the study.