Study To Assess The Clinical Benefit Of Droxidopa In Subjects With Chronic Fatigue Syndrome

SUBJECT SELECTION CRITERIA:

• Female and male outpatients between 18-65 years of age;
• Subjects must be diagnosed with chronic fatigue syndrome (Per Fukuda Criteria);
• Subjects must have neurally mediated hypotension (NMH) or neurogenic orthostatic hypotension (NOH) (confirmed via Tilt table test);
• Voluntarily read and sign an informed consent.

MAIN SUBJECT EXCLUSION CRITERIA:

• Taking a direct acting vasoconstricting agent (i.e. ephedrine or midodrine)
• Patients taking vasoconstrictor agents such as ephedrine, or midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit (Visit 2);
• Taking anti-hypertensive medication for the treatment of high blood pressure
• Women of childbearing potential who are not using a medically accepted contraception;
• Subject Restrictions: 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 throughout the study period and for 4 weeks after the last dose of investigational product. 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. 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 4 weeks after the last dose of investigational product.
• For WOCP a urine pregnancy test must be conducted at screening, baseline and study termination; the results must be negative at screening and at baseline. Any positive result will be confirmed by serum beta HCG pregnancy test.
• Sexually active males whose partner is a WOCP must agree to use condoms for the duration of the study and for 4 weeks after the last dose;
• Women who are pregnant, breast feeding, or plan to become pregnant during the course of this study;
• Have a history of closed angle glaucoma;
• Have uncontrolled supine hypertension, defined as systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg or use of ≥2 antihypertensive medications;
• Have atrial fibrillation or, in the investigator's opinion, have any other significant cardiac arrhythmia;
• Current melancholic major depressive disorder, or a previous diagnosis of psychosis, eating disorder, or bipolar disorder.
• History of substance abuse or dependence within the past two years, excluding nicotine and caffeine.
• Have a history of more than moderate alcohol consumption; (drinking in moderation is defined as having no more than 1 drink per day for women and no more than 2 drinks per day for men. This definition is referring to the amount consumed on any single day and is not intended as an average over several days)
• Known or suspected hypersensitivity to the study medication or any of its ingredients;
• Serious unstable medical illness, including cardiovascular, hepatic, renal, respiratory, or hematologic illness, or other unstable medical or psychiatric conditions that in the opinion of the investigator would compromise participation or would likely lead to hospitalization during the duration of the study.
• Subjects who have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
• Subjects who are judged before randomization to be at suicidal risk by the clinical investigator.
• Have diabetes mellitus or insipidus;
• Have a known or suspected current malignancy. Patients with a history of cancer must be symptom- and treatment-free for at least 5 years before randomization, with the exception of patients with non-melanoma, non-invasive skin cancers (such as basal cell carcinoma), who should not have had an intervention or recurrence within one year of starting the study;;
• Have 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;
• Have a serum creatinine level >1.3 mg/ml
• In the investigator's opinion, are unable to stand up without human or physical assistance;
• Conditions that Exclude a Diagnosis of CFS
• Any active medical condition that may explain the presence of chronic fatigue, such as untreated hypothyroidism, sleep apnea and narcolepsy, and iatrogenic conditions such as side effects of medication.
• Persistence of unresolved or relapsing condition that could explain the presence of chronic fatigue, Examples of illnesses that can present such a picture include some types of malignancies and chronic cases of hepatitis B or C virus infection.
• Any past or current diagnosis of a major depressive disorder with psychotic or melancholic features such as; bipolar affective disorders; schizophrenia of any subtype; delusional disorders of any subtype; dementias of any subtype; anorexia nervosa; or bulemia nervosa.
• Alcohol or other substance abuse, occurring within 2 years of the onset of chronicfatigue and any time afterwards.
• Severe obesity as defined by a body mass index [body mass index = weight in kilograms ÷ (height in meters)2] equal to or greater than 45. [Note: body mass index values vary considerably among different age groups and populations. No"normal" or "average" range of values can be suggested in a fashion that is meaningful. The BMI range of 45 or greater was selected because it clearly falls within the range of severe obesity.]