Cangrelor Neonatal PK/PD and Safety Study

Study Overview
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Brief Summary
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The purpose of this study is to assess the PK/PD and safety profile of cangrelor in neonatal participants at risk of thrombosis.

Official Title
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A Prospective, Open-Label, Single-Arm, Multi-Center Study To Assess The Pharmacokinetics/Pharmacodynamics (PK/PD) And Safety Of Different Cangrelor Doses In Neonatal Subjects At Risk Of Thrombosis

Conditions
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Partial Obstruction of Systemic to Pulmonary Artery Shunt, Complete Obstruction of Systemic to Pulmonary Artery Shunt

Intervention / Treatment
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* Drug: Cangrelor


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Males and females with congenital heart disease, and ranging in age from birth through 28 days of life Postoperative neonatal cardiac participants with placement of systemic-to-pulmonary artery palliative shunts, right ventricle to pulmonary artery palliative shunts, or ductus arteriosus stents who are at risk of thrombotic events after repair for structural congenital heart disease. Written informed consent from a parent/legal guardian Life expectancy of at least 15 days at study entry Participants will be excluded from the study if any of the following exclusion criteria apply: History of intracerebral bleed (confirmed by a ultrasound (US) of the head prior to surgery), or cerebral arteriovenous malformation, or any prior bleed with neurological deficit Gastrointestinal or urinary bleeding Cerebrovascular accident or any cerebrovascular accident with a residual neurological deficit Known congenital or acquired bleeding or clotting disorder Weight less than 2.5 kilograms (kg) Adjusted gestational age less than 37 weeks Platelet count less than 100,000 cells/microliter (µL) Chest and/or mediastinal tube blood output of greater than 3 milliliters (mL)/kg/hour (hr) at the time of cangrelor administration Participants with evidence of severe hepatic or renal failure [aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than three times normal for age or total bilirubin greater than 20 milligrams (mg)/deciliter (dL); creatinine greater than 2 times the normal upper limit] Known allergy to cangrelor or known sensitivity to any component of cangrelor Any condition that in the investigator's opinion would constitute a contraindication to participation in the study or cause inability to comply with the study requirements Participation in another investigational therapeutic drug or investigational therapeutic device trial within 30 days of starting study Participants who have been receiving warfarin (Coumadin®) therapy

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 28 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cangrelor<br>Cangrelor in up to four (4) dose cohorts consisting of a minimum of five participants in each cohort. One cohort of five participants will be enrolled at a time. Cohort 1 subjects will receive Cangrelor at 0.5 mcg/kg/min. Cohort 2 subjects will receive Cangrelor at 0.25 mcg/kg/min. Subsequent cohort dosing decisions are made at the completion of enrollment in each cohort. | Drug: Cangrelor<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total plasma concentrations of cangrelor and its primary metabolite, AR C69712, during administration and after cessation of the infusion in neonates |  | During study drug infusion through 8 hours post infusion | 
| Proportion of participants in each cohort who achieve ≥90% inhibition of final platelet aggregation as measured by light transmittance aggregometry (LTA) using 20 micromolar (µM) adenosine diphosphate (ADP) in platelet rich plasma |  | During study drug infusion through 1 hour post infusion | 
| Individual recovery of platelet function in neonates after cessation of the infusion |  | Up to 1 hour post infusion | 
| Assessment of the safety of cangrelor in neonatal participants by evaluating adverse events (AEs) and serious adverse events (SAEs) |  | from start of cangrelor infusion through 48 hours post cangrelor infusion |