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

Vascular Disease Clinical Trial

Official title:

Demonstration of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Antiplatelet Effect of PZ-128 in Subjects With Multiple Coronary Artery Disease Risk Factors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01806077
• Other study ID #: TMC-A2012-04
• Secondary ID: P50HL110789
• Status: Completed
• Phase: Phase 1
• First received: March 1, 2013
• Last updated: April 20, 2016
• Start date: April 2013
• Est. completion date: November 2014

Study information

• Verified date: April 2016
• Source: Tufts Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Data and Safety Monitoring BoardUnited States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Artery Disease Risk Factors Multiple
• Coronary Disease
• Myocardial Ischemia
• Vascular Disease
• Vascular Diseases

Intervention

Drug:
• PZ-128
Sequential single-dose escalation; 1 to 2 hour continuous intravenous infusion

Locations

Country	Name	City	State
United States	Sinai Hospital of Baltimore (Sinai Center for Thrombosis Research)	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Tufts Medical Center	National Heart, Lung, and Blood Institute (NHLBI), Sinai Hospital of Baltimore

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	30 days after drug infusion	Yes
Secondary	Pharmacokinetic profile of PZ-128		Assessments will be done up to 7 days post dosing	No
Secondary	Evaluate inhibition of ex vivo platelet function in response to multiple agonists		Assessments will be done up to 7 days post dosing	No
Secondary	Correlate PZ-128 plasma levels with inhibition of platelet aggregation		Assessments will be done up to 7 days post dosing	No
Secondary	Evaluate changes in clotting characteristics at each dose level of PZ-128 relative to baseline		Assessments will be done up to 7 days post dosing	No