Cangrelor Neonatal PK/PD and Safety Study

NCT02765633 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: MDCO-CAN-15-012016-000134-22
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Partial Obstruction of Systemic to Pulmonary Artery Shunt; Complete Obstruction of Systemic to Pulmonary Artery Shunt

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (1)

Cangrelor

EXPERIMENTAL

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

Interventions

Cangrelor DRUG

Cangrelor

Eligibility Criteria

• Age: 1 Day - 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (2)

Columbia University Medical Center

New York, New York, 10032, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Related Publications (1)

• Vargas D, Zhou H, Yu X, Diamond S, Yeh J, Allada V, Krishnamurthy G, Price M, Allen B, Alexander J, Schmidhofer J, Kreutzer J, Vincent J, Morell V, Bacha E, Diacovo T. Cangrelor PK/PD analysis in post-operative neonatal cardiac patients at risk for thrombosis. J Thromb Haemost. 2021 Jan;19(1):202-211. doi: 10.1111/jth.15141. Epub 2020 Nov 29.

  PMID: 33078501 RESULT

Related Links

• Study Record on EU Clinical Trials Register including results

MeSH Terms

Interventions

cangrelor

Study Officials

• Thomas Diacovo, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: May 6, 2016
• Study Start: January 3, 2017
• Primary Completion: August 31, 2019
• Study Completion: December 23, 2019
• Last Updated: February 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)