INCLUSION CRITERIA:
A candidate patient is eligible for inclusion, if he or she satisfies all of the following criteria.
1. The patient is a male or female aged 18 years or over;
2. A clinical diagnosis of neurogenic orthostatic hypotension (NOH) is established by physiological and neurochemical tests described below. NOH may be associated with PAF, PD, MSA, DBH deficiency, or non-diabetic, primary, chronic autonomic failure.
3. There is a documented fall in systolic blood pressure of at least 20 mm Hg, or in diastolic blood pressure of at least 10 mm Hg, after 3 minutes after upright posture;
4. The patient provides written informed consent to participate in the study and understands that one may withdraw consent at any time without prejudice to future medical care.
EXCLUSION CRITERIA:
A candidate patient is not eligible for this study, if he or she has any of the following. Patients may continue their usual medications, including drugs for PD, as long as the regimen remains the same throughout the study.
1. The patient currently takes ephedrine or midodrine. Patients taking ephedrine or midodrine must stop taking these drugs at least 2 days prior to the Baseline visit.
2. The patient currently takes anti-hypertensive medication. The use of short-acting anti-hypertensive medications at bedtime is permitted.
3. The patient currently takes a tricyclic antidepressant medication or any other norepinephrine re-uptake inhibitor.
4. The dose, frequency, or type of prescribed medication for neurogenic orthostatic hypotension has changed within two weeks of study start (except for ephedrine and midodrine).
5. The patient has a history of more than moderate alcohol consumption, as indicated by a current history of daily intake of at least 2 alcoholic drinks, past history of hospitalization for detoxification or alcohol withdrawal, or physical examination revealing stigmata of chronic alcoholism.
6. The patient has a known or suspected history of drug or substance abuse, as indicated by a current history of daily self-administration of an abused drug, past history of hospitalization for detoxification or drug withdrawal or overdose, or physical examination revealing stigmata of chronic substance abuse.
7. Women of childbearing potential (WOCP) who are not using a medically accepted contraception are excluded. Female subjects should be either post-menopausal (see below), surgically sterile, or 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.
Women over 55 years old who have not had a period for a year will be considered menopausal and do not need a pregnancy test, FSH test, or contraception. Women between 50 and 55 who have not had a period for a year will need an FSH level more than 20 mIU/mL to be considered menopausal. If the level is less than 20, a pregnancy test or contraception is required. Women between 45 and 50 who did not have a period for a year will need an FSH test and a pregnancy test. If the FSH level is more than 20, they will be considered menopausal and will not require contraception or pregnancy testing. If the FSH test is less than 20, they will need contraception or pregnancy testing.
8. 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 are excluded. The goal is to ensure that a female partner who is a WOCP is not impregnated by a male patient who has received Droxidopa, because of the remote possibility of birth defects due to effects of Droxidopa on the patient's sperm.
9. Women who are pregnant or breast feeding are excluded.
10. The patient has a known or suspected hypersensitivity to the study medication or any of its ingredients.
11. The patient has pre-existing, sustained, severe hypertension (BP greater than or equal to 180/110 mmHg in the sitting position.
12. The patient is in atrial fibrillation or, in the opinion of the Principal Investigator, the patient has any other significant cardiac arrhythmia.
13. The patient has a significant systemic, hepatic, cardiac, or renal illness, in the opinion of the Principal Investigator.
14. The patient has diabetes mellitus or diabetes insipidus. Patients with insulin-dependent diabetes mellitus are excluded. Those on an oral hypoglycemic agent may be excluded, at the discretion of the Principal Investigator.
15. The patient has a history of closed angle glaucoma.
16. The patient is known or suspected to have a malignancy.
17. The serum creatinine level is more than 130 micromol/L at the time of screening.
18. The patient has gastrointestinal condition that may, in the Principal Investigator's opinion, affect the absorption of the study drug.
19. Abnormalities on clinical examination or laboratory testing are clinically significant, in the opinion of the Principal Investigator.
20. The patient is unable to co-operate adequately because of an individual or family situation, in the opinion of the Principal Investigator.
21. The patient has a psychiatric disorder that In the Principal Investigator's opinion will interfere with the diagnosis or with the conduct of the study (e.g., schizophrenia, major depression, dementia).
22. The patient is unable or unwilling to comply with study requirements for the duration of the study.
23. The patient has 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.
24. The patient previously was enrolled in this study.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 05/05/2009