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

NCT01806077 | Completed Phase 1 DMC

• 2 other identifiers: TMC-A2012-04P50HL110789
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Vascular Disease; Coronary Artery Disease Risk Factors Multiple

Keywords

Cardiovascular Diseases; Vascular Diseases; Coronary Artery Disease; Coronary Disease; Arteriosclerosis; Platelet Aggregation Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Pharmacokinetic profile of PZ-128

  Assessments will be done up to 7 days post dosing

• Evaluate inhibition of ex vivo platelet function in response to multiple agonists

  Assessments will be done up to 7 days post dosing

• Correlate PZ-128 plasma levels with inhibition of platelet aggregation

  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

  Assessments will be done up to 7 days post dosing

Study Arms (1)

PZ-128

EXPERIMENTAL

Drug: PZ-128

Interventions

PZ-128 DRUG

Sequential single-dose escalation; 1 to 2 hour continuous intravenous infusion

PZ-128

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tufts Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Sinai Hospital of Baltimore: collaborator

Study Sites (1)

Sinai Hospital of Baltimore (Sinai Center for Thrombosis Research)

Baltimore, Maryland, 21215, United States

Location

Related 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.

  PMID: 26681756 BACKGROUND

MeSH Terms

Conditions

Vascular Diseases; Cardiovascular Diseases; Coronary Artery Disease; Coronary Disease; Arteriosclerosis

Interventions

PZ-128 peptide

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Arterial Occlusive Diseases

Study Officials

• Paul A. Gurbel, MD

  Sinai Hospital of Baltimore (Sinai Center for Thrombosis Research)

  PRINCIPAL INVESTIGATOR

• Athan Kuliopulos, MD, PhD

  Tufts Medical Center (Hemostasis and Thrombosis Laboratory)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2013
• First Posted: March 7, 2013
• Study Start: April 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: April 21, 2016

Record last verified: 2016-04

Locations

US (1)