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

Tracking Information
First Submitted Date ICMJE	March 1, 2013
First Posted Date ICMJE	March 7, 2013
Last Update Posted Date	April 21, 2016
Study Start Date ICMJE	April 2013
Actual Primary Completion Date	November 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 5, 2013)	Summary of Participants Experience with Safety and Tolerability [ Time Frame: 30 days after drug infusion ]; 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).
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01806077 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 5, 2013)	Pharmacokinetic profile of PZ-128 [ Time Frame: Assessments will be done up to 7 days post dosing ]; Evaluate inhibition of ex vivo platelet function in response to multiple agonists [ Time Frame: Assessments will be done up to 7 days post dosing ]; Correlate PZ-128 plasma levels with inhibition of platelet aggregation [ Time Frame: Assessments will be done up to 7 days post dosing ]; 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 ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety Study of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk Factors
Official Title ICMJE	Demonstration of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Antiplatelet Effect of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk Factors
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: Single (Participant); Primary Purpose: Treatment
Condition ICMJE	Vascular Disease; Coronary Artery Disease Risk Factors Multiple
Intervention ICMJE	Drug: PZ-128; Sequential single-dose escalation; 1 to 2 hour continuous intravenous infusion
Study Arms	Experimental: PZ-128; Intervention: Drug: PZ-128
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 21, 2014)	32
Original Estimated Enrollment ICMJE; (submitted: March 5, 2013)	34
Actual Study Completion Date	November 2014
Actual Primary Completion Date	November 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 75 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01806077
Other Study ID Numbers ICMJE	TMC-A2012-04; P50HL110789 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Tufts Medical Center
Study Sponsor ICMJE	Tufts Medical Center
Collaborators ICMJE	National Heart, Lung, and Blood Institute (NHLBI); Sinai Hospital of Baltimore
Investigators ICMJE	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)
PRS Account	Tufts Medical Center
Verification Date	April 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP