NCT02522208

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1 heart-failure

Timeline
Completed

Started Sep 2015

Shorter than P25 for phase_1 heart-failure

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 5, 2015

Completed
8 days until next milestone

First Posted

Study publicly available on registry

August 13, 2015

Completed
19 days until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

November 8, 2016

Status Verified

November 1, 2016

Enrollment Period

7 months

First QC Date

August 5, 2015

Last Update Submit

November 7, 2016

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

  • Pulmonary Artery (PA) Systolic Pressure change from baseline to each post dose timepoint for 28 hours

    assess the treatment effect of BiDil and BiDil XR on Pulmonary Artery Systolic Pressure (PASP) by Doppler echocardiography

    6 days

Secondary Outcomes (2)

  • 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

Other Outcomes (6)

  • Treatment effect on ejection fraction

    6 days

  • Treatment effect on Mean PA pressure

    6 days

  • Treatment effect on PA diastolic pressure

    6 days

  • +3 more other outcomes

Study Arms (2)

BiDil Extended Release (XR)

EXPERIMENTAL

BiDil XR isosorbide dinitrate 40 mg and hydralazine hydrochloride 75 mg 2 capsules 9 hours apart for one day

Drug: BiDil XRDrug: BiDil Immediate Release (IR)

BiDil Immediate Release (IR)

ACTIVE COMPARATOR

BiDil isosorbide dinitrate 20 mg and hydralazine hydrochloride 37.5 mg 3 tablets 6 hours apart for one day

Drug: BiDil XRDrug: BiDil Immediate Release (IR)

Interventions

BiDil XRDRUG

fixed combination capsule

Also known as: BiDil capsules, hydralazine HCl + isosorbide dinitrate
BiDil Extended Release (XR)BiDil Immediate Release (IR)
BiDil Immediate Release (IR)DRUG

fixed combination tablet

Also known as: BiDil tablets, hydralazine HCl + isosorbide dinitrate
BiDil Extended Release (XR)BiDil Immediate Release (IR)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +4 more criteria

You may not qualify if:

  • 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.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Pinnacle Research Group, LLC

Anniston, Alabama, 36207, United States

Location

Linfritz Research Institue Inc

Coral Gables, Florida, 33134, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Morehouse School of Medicine

Atlanta, Georgia, 30310, United States

Location

Center for Medical Research, LLC

Providence, Rhode Island, 02908, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

HydralazineIsosorbide Dinitrateisosorbide-hydralazine combination

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

PhthalazinesPyridazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsosorbideSorbitolSugar AlcoholsAlcoholsOrganic ChemicalsCarbohydrates

Study Officials

  • Steve D Caras, MD, PhD

    Arbor Pharmaceuticals

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 5, 2015

First Posted

August 13, 2015

Study Start

September 1, 2015

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

November 8, 2016

Record last verified: 2016-11

Data Sharing

IPD Sharing
Will not share

Locations

US(5)