Safety Study of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk Factors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Tufts Medical Center
Sponsor:
Collaborators:
Sinai Hospital of Baltimore
Information provided by (Responsible Party):
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT01806077
First received: March 1, 2013
Last updated: August 12, 2014
Last verified: August 2014
  Purpose

This study is a Phase I, intravenous, single-dose escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of PZ-128 (pepducin inhibitor of PAR1) in subjects with vascular disease or who have 2 or more coronary artery disease (CAD) risk factors.


Condition Intervention Phase
Vascular Disease
Coronary Artery Disease Risk Factors Multiple
Drug: PZ-128
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Demonstration of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Antiplatelet Effect of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk Factors

Resource links provided by NLM:


Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:
  • Summary of Participants Experience with Safety and Tolerability [ Time Frame: 30 days after drug infusion ] [ Designated as safety issue: Yes ]
    Safety and tolerability of a single dose of PZ-128 as determined by adverse event reporting, clinical laboratory results, vital signs, physical examination, pulmonary function tests and electrocardiograms (ECGs).


Secondary Outcome Measures:
  • Pharmacokinetic profile of PZ-128 [ Time Frame: Assessments will be done up to 7 days post dosing ] [ Designated as safety issue: No ]
  • Evaluate inhibition of ex vivo platelet function in response to multiple agonists [ Time Frame: Assessments will be done up to 7 days post dosing ] [ Designated as safety issue: No ]
  • Correlate PZ-128 plasma levels with inhibition of platelet aggregation [ Time Frame: Assessments will be done up to 7 days post dosing ] [ Designated as safety issue: No ]
  • Evaluate changes in clotting characteristics at each dose level of PZ-128 relative to baseline [ Time Frame: Assessments will be done up to 7 days post dosing ] [ Designated as safety issue: No ]

Estimated Enrollment: 31
Study Start Date: April 2013
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PZ-128 Drug: PZ-128
Sequential single-dose escalation; 1 to 2 hour continuous intravenous infusion

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects between the ages of 18 to 75 with documented vascular disease (peripheral vascular disease, carotid artery disease or coronary artery disease) or 2 or more coronary artery risk factors.
  • Women of childbearing potential must have a negative pregnancy test prior to enrollment and immediately before drug administration and agree to use two methods of effective barrier contraception, or a hormonal contraceptive to prevent pregnancy throughout the study.
  • The subject is able to read and give written informed consent and has signed and dated an informed consent document and authorization permitting release of personal health information approved by the Investigator's Institutional Review Board (IRB).

Exclusion Criteria:

  • The subject has participated in an investigational drug study within the last 30 days.
  • The subject has a medical or surgical condition that may impair drug absorption or metabolism.
  • Anticoagulants, P2Y12 inhibitors, nonsteroidal antiinflammatory drugs (no more than three times a week) or any other drug that the investigator deems to have potential interaction with platelets or PAR-1 receptor inhibition are prohibited from 2 weeks prior to study drug dosing through 2 weeks post dosing. Aspirin is allowed.
  • The subject has previous history of anaphylaxis to drugs or any environmental stimuli including foods or hymenoptera (e.g., ants, bees, wasps) stings.
  • Asthma requiring bronchodilator/inhaler therapy.
  • Currently smoking ≥2 pack/day.
  • Herbal supplements (i.e., Fish Oil/Omega-3, St. John's Wart, Ginseng, Garlic, Ginkgo, Saw Palmetto, Echinacea, Yohimbine, Licorice, and Black Cohosh) are prohibited from 1 week prior to dosing through 24 hours post dosing.
  • Prior history or clinical suspicion of cerebral vascular malformations, intracranial tumor, transient ischemic attack, stroke, gastric ulcers and any form of bleeding disorder.
  • Prior history of myocardial infarction within the last 3 months or unstable angina.
  • Thrombocytopenia defined as a platelet count of <130,000/mm3 or low hematocrit defined as <30%.
  • Renal function: serum creatinine >1.5 x ULN. However, subjects with an estimated creatinine clearance eGFR ≥60 mL/min, calculated using the Cockcroft-Gault formula, are eligible.
  • Liver enzymes ≥ 3 x upper limit of normal.
  • Alcohol consumption within 48 hrs prior to dosing, and for the duration of the in-house study period.
  • Evidence of history of substance or alcohol abuse at screening, including positive urine test results for drugs or positive breath test for alcohol.
  • Uncontrolled hypertension or hypotension defined as a sustained supine systolic pressure >160 mmHg or <100 mmHg; or a diastolic pressure >90 mmHg or < 50 mmHg.
  • International normalized ratio (INR) >1.5
  • Poor venous access (i.e., insufficient for intravenous drug delivery).
  • History of hepatitis or HIV.
  • The subject has undergone an invasive surgical procedure within the last 3 months, is anticipating one during the course of their study participation or is planning to have one within 1 month post dosing with the study drug.
  • The subject has any condition which could interfere with or for which the treatment might interfere with the conduct of the study, or which would, in the opinion of the Investigator increase the risk of the subject's participation in the study. This would include, but is not limited to alcoholism, drug dependency or abuse, psychiatric disease, epilepsy or any unexplained blackouts, previous hypersensitivity to drugs, and severe asthma.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01806077

Locations
United States, Maryland
Sinai Hospital of Baltimore (Sinai Center for Thrombosis Research) Recruiting
Baltimore, Maryland, United States, 21215
Contact: Kevin Bliden, MBA    410-601-4795    kbliden@lifebridgehealth.org   
Principal Investigator: Paul A. Gurbel, MD         
Sponsors and Collaborators
Tufts Medical Center
Sinai Hospital of Baltimore
Investigators
Principal Investigator: Paul A. Gurbel, MD Sinai Hospital of Baltimore (Sinai Center for Thrombosis Research)
Study Director: Athan Kuliopulos, MD, PhD Tufts Medical Center (Hemostasis and Thrombosis Laboratory)
  More Information

No publications provided

Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT01806077     History of Changes
Other Study ID Numbers: TMC-A2012-04, P50HL110789
Study First Received: March 1, 2013
Last Updated: August 12, 2014
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Institutional Review Board

Keywords provided by Tufts Medical Center:
Cardiovascular Diseases
Vascular Diseases
Coronary Artery Disease
Coronary Disease
Arteriosclerosis
Platelet Aggregation Inhibitors

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Vascular Diseases
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 25, 2014