Safety Study of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk Factors
Primary Purpose
Vascular Disease, Coronary Artery Disease Risk Factors Multiple
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PZ-128
Sponsored by
About this trial
This is an interventional treatment trial for Vascular Disease focused on measuring Cardiovascular Diseases, Vascular Diseases, Coronary Artery Disease, Coronary Disease, Arteriosclerosis, Platelet Aggregation Inhibitors
Eligibility 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.
Sites / Locations
- Sinai Hospital of Baltimore (Sinai Center for Thrombosis Research)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PZ-128
Arm Description
Outcomes
Primary Outcome Measures
Summary of Participants Experience with Safety and Tolerability
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
Evaluate inhibition of ex vivo platelet function in response to multiple agonists
Correlate PZ-128 plasma levels with inhibition of platelet aggregation
Evaluate changes in clotting characteristics at each dose level of PZ-128 relative to baseline
Full Information
NCT ID
NCT01806077
First Posted
March 1, 2013
Last Updated
April 20, 2016
Sponsor
Tufts Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Sinai Hospital of Baltimore
1. Study Identification
Unique Protocol Identification Number
NCT01806077
Brief Title
Safety Study of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk Factors
Official Title
Demonstration of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Antiplatelet Effect of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk Factors
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tufts Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Sinai Hospital of Baltimore
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vascular Disease, Coronary Artery Disease Risk Factors Multiple
Keywords
Cardiovascular Diseases, Vascular Diseases, Coronary Artery Disease, Coronary Disease, Arteriosclerosis, Platelet Aggregation Inhibitors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
Participant
Allocation
N/A
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PZ-128
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
PZ-128
Intervention Description
Sequential single-dose escalation; 1 to 2 hour continuous intravenous infusion
Primary Outcome Measure Information:
Title
Summary of Participants Experience with Safety and Tolerability
Description
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).
Time Frame
30 days after drug infusion
Secondary Outcome Measure Information:
Title
Pharmacokinetic profile of PZ-128
Time Frame
Assessments will be done up to 7 days post dosing
Title
Evaluate inhibition of ex vivo platelet function in response to multiple agonists
Time Frame
Assessments will be done up to 7 days post dosing
Title
Correlate PZ-128 plasma levels with inhibition of platelet aggregation
Time Frame
Assessments will be done up to 7 days post dosing
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul A. Gurbel, MD
Organizational Affiliation
Sinai Hospital of Baltimore (Sinai Center for Thrombosis Research)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Athan Kuliopulos, MD, PhD
Organizational Affiliation
Tufts Medical Center (Hemostasis and Thrombosis Laboratory)
Official's Role
Study Director
Facility Information:
Facility Name
Sinai Hospital of Baltimore (Sinai Center for Thrombosis Research)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
26681756
Citation
Gurbel PA, Bliden KP, Turner SE, Tantry US, Gesheff MG, Barr TP, Covic L, Kuliopulos A. Cell-Penetrating Pepducin Therapy Targeting PAR1 in Subjects With Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 2016 Jan;36(1):189-97. doi: 10.1161/ATVBAHA.115.306777.
Results Reference
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Safety Study of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk Factors
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