Safety of PZ-128 in Subjects Undergoing Non-Emergent Percutaneous Coronary Intervention
Condition: Arterial Occlusive Diseases; Coronary Artery Disease; Coronary Disease; Arteriosclerosis; Heart Diseases; Myocardial Ischemia; Vascular Diseases; Acute Coronary Syndrome
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Acute Coronary Syndrome; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Ischemia
Intervention: PZ-128; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Platelets; Platelet Aggregation Inhibitors; Protease-Activated Receptor 1; Hemorrhage

Summary:

      The object of the study is to determine whether different doses of PZ-128, when added to
      standard medical care in persons undergoing cardiac catheterization/percutaneous coronary
      intervention, will increase the risk of bleeding.

      A secondary objective is to determine whether patients treated with PZ-128 have fewer cardiac
      events such as heart attack, bypass surgery or stroke compared with those persons treated
      with the standard of care.
    

Eligibility criteria:

        Inclusion Criteria:

          1. The subject is at least 18 years of age and may be of either sex/gender and of any
             race and ethnicity.

          2. The subject is scheduled to undergo non-emergent PCI or non-emergent cardiac
             catheterization with the intention of performing PCI. The following classifications of
             the urgency of the procedure at the time the operator decides to perform it will be
             used for randomization stratification:

               -  Elective: The cardiac catheterization procedure ± PCI can be performed on an
                  outpatient basis or during a subsequent hospitalization without significant risk
                  of MI or death. For stable inpatients, this is a procedure that is performed
                  during the hospitalization for convenience and ease of scheduling only and not
                  because the subject's clinical situation demands that the procedure be performed
                  prior to discharge.

             OR

               -  Urgent: The cardiac catheterization ± PCI procedure should be performed on an
                  inpatient basis and before discharge because of significant concerns about the
                  risk of myocardial ischemia, MI and/or death. For subjects who are outpatients or
                  in the emergency department at the time that the cardiac catheterization is
                  requested, this is a procedure that would warrant hospital admission based on
                  clinical presentation.

          3. There is no anticipation that the subject would require treatment with a GP IIb/IIIa
             inhibitor prior to the initiation of the cardiac catheterization ± PCI procedure if
             the subject were not a participant in the current research study, and no anticipation
             of use during the procedure.

          4. The subject is willing and able to give appropriate informed consent and complete all
             study-related procedures, and able to adhere to dosing and visit schedules (i.e.,
             subject signs an approved informed consent document(s) and provides HIPAA
             authorization);

          5. The subject will undergo all of the pre-enrollment parameters according to the study
             protocol prior to randomization and have them completed within 14 days prior to the
             scheduled cardiac catheterization ± PCI procedure and study drug administration.

          6. Women of childbearing potential (all postmenarchal women who are <1 year menopausal or
             who have not had surgical sterilization or a hysterectomy are considered to be women
             of child-bearing potential) must agree to use a medically accepted method of
             contraception from the time written informed consent is given up until 90 days
             following the study drug administration.

        Subject Exclusion Criteria:

        The subject will be excluded from entry if any of the criteria listed below are met:

        (General Exclusions)

          1. Subject is pregnant, intends to become pregnant or is breast-feeding (all women of
             child-bearing potential must have a negative pregnancy test result confirmed prior to
             randomization and it must be repeated to be within 24 hours prior to the study drug
             administration if necessary).

          2. Any of the following allergy history(s):

               -  History of an allergic reaction* or contraindication to any of the following
                  protocol-directed drugs: aspirin, heparin, P2Y12 inhibitor (clopidogrel,
                  prasugrel, ticagrelor), antihistamines (benadryl, famotidine); or

               -  History of an allergic reaction* to contrast media; or

               -  History of an allergic reaction* to a drug which required emergency medical
                  treatment;

               -  History of an allergic reaction* to a Hymenoptera sting which currently
                  necessitates the subject to carry an EpiPen/injector or the subject has been
                  prescribed one to treat an allergic reaction to a sting.

                    -  An allergic (anaphylactic) reaction is characterized by an adverse local or
                       general response from exposure to an allergen involving skin/mucosal tissue
                       manifestations (hives, pruritus, flushing, angioedema), and/or respiratory
                       compromise (dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory
                       flow, hypoxemia), and/or hemodynamic effects (hypo/hypertension, hypotonia,
                       syncope).

          3. Participation in another research study of investigational therapy (drug or device)
             within the past 30 days prior to randomization or planned use of other investigational
             therapy(s) during this research study (until 90 days following the study drug
             administration).

          4. Subject is part of the study staff personnel directly involved with this trial, or is
             a family member of the study staff (clinical site or sponsor).

          5. Prior enrollment (randomization) in this research study.

          6. Any condition which could interfere with, or the treatment for which might interfere
             with, the conduct of the research study or which would, in the opinion of the
             investigator, unacceptably increase the subject's risk by participating in the
             research study. This would include, but is not limited to alcoholism, drug dependency
             or abuse, psychiatric disease, epilepsy or any unexplained blackouts.

             (Exclusionary Prior/Concomitant Conditions)

          7. Evidence of an ST-segment elevation myocardial infarction (STEMI) on presentation or
             during current hospitalization or a history of STEMI within the past 30 days prior to
             randomization.

          8. Subject is scheduled to undergo PCI for known unprotected left main coronary artery
             (LMCA) disease (i.e., left main stenosis ≥50% not protected by at least 1 patent
             bypass graft).

          9. Any history of a prior stroke (hemorrhagic or ischemic) or transient ischemic attack
             (TIA) of any etiology.

         10. Cardiogenic or any type of shock on presentation or during current hospitalization
             (i.e., systolic blood pressure <90 mm Hg requiring vasopressor or hemodynamic
             support).

         11. History of heparin-induced thrombocytopenia (HIT).

         12. Any active bleeding within the past 30 days prior to randomization.

         13. Any condition or personal belief (e.g., Jehovah's Witness) which would interfere with
             the subject's ability or willingness to undergo a blood transfusion.

         14. Any of the following conditions associated with increased risk of bleeding:

               1. history of intracranial, intraocular, spinal, retroperitoneal or atraumatic
                  intra- articular bleeding;

               2. gastrointestinal bleeding within the past 30 days prior to randomization;

               3. gastric or duodenal ulcer disease verified by endoscopy or barium meal contrast
                  technique within the past 6 months prior to randomization;

               4. history of bleeding disorder or diathesis;

               5. major surgical procedure or trauma within the past 60 days prior to randomization
                  or a planned surgical procedure to take place within 30 days following the study
                  drug administration;

               6. history or suspicion of intracranial neoplasm, arteriovenous malformation, or
                  aneurysm; or

               7. clinical finding(s) in the judgment of the investigator that poses an increased
                  risk of bleeding.

         15. Sustained severe hypertension: systolic blood pressure >185 mm Hg or diastolic blood
             pressure >105 mm Hg with or without anti-hypertensive treatment (as demonstrated by
             repeated BP measurements >185/105 mm Hg including the final BP measurement before
             randomization).

         16. Hypotension: systolic blood pressure <95 mm Hg (as demonstrated by repeated systolic
             BP measurements <95 mm Hg including the final systolic BP measurement prior to
             randomization).

         17. Known active hepatobiliary disease, or known unexplained persistent increase in serum
             alanine aminotransferase (ALT) or aspartate aminotransferase (AST) activity to ≥2.5
             times the upper limit of the reference range within the past 30 days prior to
             randomization.

         18. Hemoglobin <10 g/dL or hematocrit <30%.

         19. Platelet count <75,000/mm3.

         20. Stage 4-5 Chronic Kidney Disease (National Kidney Foundation) or on dialysis.

         21. Active sepsis or suspected sepsis.

         22. Body weight <60 kg or >175 kg.

         23. Current evidence of invasive cancer (persistent disease excluding basal cell carcinoma
             of the skin) or treatment for invasive cancer within the past 6 months prior to
             randomization.

         24. Left ventricular ejection fraction <25% if known (any imaging technique) or New York
             Heart Association (NYHA) Class IV congestive heart failure.

             (Exclusionary Prior/Concomitant/Anticipated Medication/Therapy)

         25. Coronary interventional procedure of any kind within the past 30 days prior to
             randomization.

         26. Anticipated subsequent staged multi-vessel PCI within 30 days following the study drug
             administration.

         27. History of treatment with any parenteral GP IIb/IIIa inhibitor (GPI) within the past
             30 days prior to randomization. (As stated in the Inclusion section, the planned
             treatment with a GPI prior to initiation of the cardiac catheterization ± PCI is not
             allowed; however, GPI for thrombotic bailout may be used during the PCI at the
             investigator's discretion).

         28. Concurrent or anticipated treatment with a parenteral direct thrombin inhibitor (e.g.,
             bivalirudin) for the cardiac catheterization ± PCI procedure.

         29. History of treatment with another PAR1 inhibitor within the past 60 days prior to
             randomization or the concurrent/anticipated use after randomization up until 30 days
             following the study drug administration.

         30. History of treatment with another IV anti-platelet drug within 30 days prior to
             randomization or the concurrent/anticipated use after randomization up until 30 days
             following the study drug administration.

         31. Any of the following anticoagulant or thrombolytic/fibrinolytic treatment(s):

               -  History of treatment with warfarin within 5 days prior to randomization or the
                  concurrent/anticipated use after randomization up until 2 days following the
                  study drug administration; or

               -  History of treatment with oral Factor Xa or direct thrombin inhibitors within 2
                  days prior to randomization or the concurrent/anticipated use after randomization
                  up until 2 days following the study drug administration; or

               -  History of treatment with thrombolytic/fibrinolytic agents within 7 days prior to
                  randomization or the concurrent/anticipated use of any of those agents after
                  randomization up until 30 days following the study drug administration.