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

November 7, 2016 updated by: Arbor Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Anniston, Alabama, United States, 36207
        • Pinnacle Research Group, LLC
    • Florida
      • Coral Gables, Florida, United States, 33134
        • Linfritz Research Institue Inc
      • Jacksonville, Florida, United States, 32216
        • Jacksonville Center for Clinical Research
    • Georgia
      • Atlanta, Georgia, United States, 30310
        • Morehouse School of Medicine
    • Rhode Island
      • Providence, Rhode Island, United States, 02908
        • Center for Medical Research, LLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.
  • Negative human chorionic gonadotropin (hCG) pregnancy test.
  • Females must agree to avoid becoming pregnant or males must agree to use appropriate contraceptive methods with his partner(s), during the study and up to post 30 days from last dose of study drug.
  • Females must be:
  • unable to have children or
  • where the partner is sterile OR
  • willing to remain abstinent OR
  • willing to use two effective methods of birth control.
  • Willing and able to be confined for inpatient study periods and agree to study restrictions
  • Ability to grant voluntary informed consent to participate in the study.

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: BiDil Extended Release (XR)
BiDil XR isosorbide dinitrate 40 mg and hydralazine hydrochloride 75 mg 2 capsules 9 hours apart for one day
Drug: BiDil XR
fixed combination capsule
Other Names:
  • BiDil capsules, hydralazine HCl + isosorbide dinitrate
Drug: BiDil Immediate Release (IR)
fixed combination tablet
Other Names:
  • BiDil tablets, hydralazine HCl + isosorbide dinitrate
Active Comparator: BiDil Immediate Release (IR)
BiDil isosorbide dinitrate 20 mg and hydralazine hydrochloride 37.5 mg 3 tablets 6 hours apart for one day
Drug: BiDil XR
fixed combination capsule
Other Names:
  • BiDil capsules, hydralazine HCl + isosorbide dinitrate
Drug: BiDil Immediate Release (IR)
fixed combination tablet
Other Names:
  • BiDil tablets, hydralazine HCl + isosorbide dinitrate

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
6 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Comparison of Maximum observed effect (Emax) on PA systolic pressure vs maximum blood concentration (Cmax)
Time Frame: 6 days
examine the relationship between the blood concentrations of each active treatment group and the changes in PASP
6 days
Comparison of the area under the effect curve (AUEC) on PA systolic pressure versus AUC (the area under the curve) for blood
Time Frame: 6 days
To examine the relationship between the blood concentrations of each active treatment group and the changes in PASP
6 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Treatment effect on ejection fraction
Time Frame: 6 days
assessing the treatment effect of BiDil and BiDil XR on other central hemodynamic measures (such as ejection fraction) and examining the relationship between the plasma or blood concentrations of each treatment group and each of these central hemodynamic measure
6 days
Treatment effect on Mean PA pressure
Time Frame: 6 days
assessing the treatment effect of BiDil and BiDil XR on other central hemodynamic measures (such as ejection fraction) and examining the relationship between the plasma or blood concentrations of each treatment group and each of these central hemodynamic measure
6 days
Treatment effect on PA diastolic pressure
Time Frame: 6 days
assessing the treatment effect of BiDil and BiDil XR on other central hemodynamic measures (such as ejection fraction) and examining the relationship between the plasma or blood concentrations of each treatment group and each of these central hemodynamic measure
6 days
Treatment effect on Pulmonary vascular resistance
Time Frame: 6 days
assessing the treatment effect of BiDil and BiDil XR on other central hemodynamic measures (such as ejection fraction) and examining the relationship between the plasma or blood concentrations of each treatment group and each of these central hemodynamic measure
6 days
Treatment effect on Right atrial pressure
Time Frame: 6 days
assessing the treatment effect of BiDil and BiDil XR on other central hemodynamic measures (such as ejection fraction) and examining the relationship between the plasma or blood concentrations of each treatment group and each of these central hemodynamic measure
6 days
Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability
Time Frame: 12 days
to compare the safety and tolerability of BiDil XR capsules, as measured by treatment-emergent AEs
12 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Arbor Pharmaceuticals, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Steve D Caras, MD, PhD, Arbor Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 5, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 11, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 13, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 8, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 7, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AR06.009

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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