Randomized, Open-Label, Daily Dose, 2-sequence, 2-way Crossover Pharmacodynamic and Pharmacokinetic Study of BiDil XR Capsules and Commercial BiDil Tablets in Self-identified Black Patients, Who Are Slow Acetylators, With Heart Failure
Overview
- Phase
- Phase 1
- Intervention
- BiDil XR
- Conditions
- Heart Failure
- Sponsor
- Arbor Pharmaceuticals, Inc.
- Enrollment
- 12
- Locations
- 5
- Primary Endpoint
- Pulmonary Artery (PA) Systolic Pressure change from baseline to each post dose timepoint for 28 hours
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This study will investigate cardiovascular parameters using echocardiographic and pharmacokinetics during a daily dose of BiDil and BiDil Extended Release (XR) compared to a study drug free day.
Detailed Description
A multiple-center, open-label, randomized, daily dose, two-sequence, two-way crossover pharmacodynamics (PD) and pharmacokinetic (PK) study of BiDil XR capsules and commercial BiDil tablets in Self-identified Black Patients, who are Slow Acetylators, with Heart Failure and have not received BiDil, isosorbide dinitrate (ISDN), or hydralazine hydrochloride (HCl) for at least 30 days prior to screening. The study consists of two doses of BiDil XR capsules (dosed at 0 hr and 9 hr) and three doses of BiDil tablets (dosed at 0 hr, 6 hr and 12 hr).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Self-identified Black, stable, chronic heart failure male or female subjects classified as having New York Heart Association (NYHA) Class II or III, diagnosed at least 3 months prior to Screening.
- •Clinically stable outpatient, receiving standard, stable treatment regimen for heart failure (HF), at least 2 weeks prior to screening and throughout the duration of the trial. Subjects receiving beta-blockers must have been taking these for at least 3 months.
- •All other medications must have been at a stable dose for at least 2 weeks prior to first dose
- •Subjects must not have received BiDil, isosorbide dinitrate or hydralazine HCl for at least 30 days prior to Screening
- •Have an adequate and demonstrable baseline Tricuspid regurgitation jet, visible inferior vena cava, and adequate right heart echocardiogram (with or without saline bubble contrast) allowing measurements to be made.
- •Baseline PA systolic pressures \> 35 mmHg
- •Slow acetylator
- •Adult subjects at least 18 years old or state-specific age of majority.
- •Clinical lab tests negative for HIV, Hepatitis B surface antigen and Hepatitis C antibody.
- •Urine testing negative for alcohol and drugs of abuse.
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.
Arms & Interventions
BiDil Extended Release (XR)
BiDil XR isosorbide dinitrate 40 mg and hydralazine hydrochloride 75 mg 2 capsules 9 hours apart for one day
Intervention: BiDil XR
BiDil Extended Release (XR)
BiDil XR isosorbide dinitrate 40 mg and hydralazine hydrochloride 75 mg 2 capsules 9 hours apart for one day
Intervention: BiDil Immediate Release (IR)
BiDil Immediate Release (IR)
BiDil isosorbide dinitrate 20 mg and hydralazine hydrochloride 37.5 mg 3 tablets 6 hours apart for one day
Intervention: BiDil XR
BiDil Immediate Release (IR)
BiDil isosorbide dinitrate 20 mg and hydralazine hydrochloride 37.5 mg 3 tablets 6 hours apart for one day
Intervention: BiDil Immediate Release (IR)
Outcomes
Primary Outcomes
Pulmonary Artery (PA) Systolic Pressure change from baseline to each post dose timepoint for 28 hours
Time Frame: 6 days
assess the treatment effect of BiDil and BiDil XR on Pulmonary Artery Systolic Pressure (PASP) by Doppler echocardiography
Secondary Outcomes
- Comparison of Maximum observed effect (Emax) on PA systolic pressure vs maximum blood concentration (Cmax)(6 days)
- Comparison of the area under the effect curve (AUEC) on PA systolic pressure versus AUC (the area under the curve) for blood(6 days)