Pharmacodynamic and Pharmacokinetic Study of BiDil Extended-release Capsules and Commercial BiDil Tablets

Exclusion Criteria

• •Have significant valvular heart disease, hemodynamically significant obstructive hypertrophic cardiomyopathy, active myocarditis, or uncontrolled hypertension.
• •Presence of severe, clinical right heart failure.
• •Symptoms of unstable angina, a myocardial infarction, cardiac surgery, or percutaneous coronary intervention within 1 month prior to Screening
• •Have coronary artery disease likely to require coronary artery bypass grafting or percutaneous coronary intervention during the ensuing 3 months.
• •Had cardiac arrest or a sustained ventricular tachycardia considered life threatening and requiring intervention within 3 months, unless treated with implantable cardioverter-defibrillator.
• •other causes of pulmonary hypertension that may confound pharmacodynamic assessments of heart failure
• •Active malignancy or any non-cardiac life-limiting disease.
• •Have significant hepatic, renal, or other disease that might confound the study results or present a risk to the subject.
• •Had a stroke within the past 3 months.
• •Received parenteral inotropic therapy within 1 month.
• •Likelihood of undergoing cardiac transplantation or circulatory assist device implant over the ensuing 3 months.
• •Symptomatic hypotension or blood pressure less than 110/70 mmHg at Screening.
• •Any condition or risk factor which would jeopardize the evaluation of efficacy or safety or the ability to obtain effective echocardiography results.
• •Currently require riociguat, hydralazine HCl, long-acting nitrates like ISDN, isosorbide mononitrate or sustained release nitroglycerin or phosphodiesterase 5 inhibitors.
• •Alcohol or drug abuse within 1 year of study participation.
• •Hypersensitivity, allergy, idiosyncratic reaction or adverse reaction to caffeine (if slow acetylator test is required), ISDN, hydralazine HCl, or any compounds with similar chemical characteristics.
• •Received investigational drug within 30 days.
• •Donated one pint or more of blood, plasma, or platelets within 30 days.
• •Any subject who, in the opinion of the Investigator, cannot follow instructions.
• •Pregnant, lactating or plan to get pregnant during the study
• •History of lupus erythematous or lupus like syndrome.
• •Use of herbal preparations, grapefruit, grapefruit juice, Seville oranges/juice or use of phosphodiesterase inhibitors within 2 weeks of first dose of study drug and throughout study.
• •Employee of the Sponsor, investigative site or contract research organization.