Cangrelor to Clopidogrel or Prasugrel Transition Study

NCT01979445 | Completed Phase 2 Results

• 1 other identifier: MDCO-CAN-13-02
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

There are two separate objectives in this study:

1. 1.To demonstrate the pharmacodynamic (PD) profile when participants treated with cangrelor are switched to oral prasugrel 60 mg administered 30 minutes (min) after cangrelor infusion is discontinued
2. 2.To demonstrate the PD profile when participants treated with cangrelor are switched to oral clopidogrel 600 mg administered during or immediately after cangrelor infusion.

Conditions

Coronary Artery Disease (CAD)

Keywords

CAD

Outcome Measures

Primary Outcomes (2)

• Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone

  A reference point for prasugrel or clopidogrel was chosen for comparison and designated at 6 or 5.5 hrs after the administration of prasugrel or clopidogrel as the reference for the effect of the oral drug. Platelet function was assessed using light transmittance aggregometry (LTA). LTA measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was expressed as % aggregation in response to 20 micromolar (μM) adenosine diphosphate (ADP) at 300 seconds (sec) (final/terminal aggregation response).

  Day 1 at 5.5 or 6 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 2.25, 2.5, 2.75, 3, 4, and 5.5 hrs after initiation of cangrelor infusion

• Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone

  A reference point for cangrelor was chosen for comparison and designated as the administration time of prasugrel 60 mg or clopidogrel 600 mg (2.5, 2, 1.5, or 1 hrs). Platelet function was assessed using LTA. LTA measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was examined using LTA and expressed as % aggregation in response to 20 μM ADP at 300 sec (final/terminal aggregation response).

  Day 1 at 1, 1.5, 2, or 2.5 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 1.75 and 2 hrs after initiation of cangrelor infusion

Secondary Outcomes (3)

• Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor to Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone Determined By VerifyNow P2Y12 Assay

  Day 1 at 5.5 or 6 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 2.25, 2.5, 2.75, 3, 4, and 5.5 hrs after initiation of cangrelor infusion

• Extent of Preservation of Platelet Inhibitory Effect of Cangrelor Treatment After Prasugrel or Clopidogrel Compared to Treatment With Cangrelor Alone Determined By VerifyNow P2Y12 Assay

  Day 1 at 1, 1.5, 2, or 2.5 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 1.75 and 2 hrs after initiation of cangrelor infusion

• Bleeding Events In Accordance With GUSTO Scale

  Screening through the follow-up period (5 to 7 days after Day 1)

Study Arms (4)

Prasugrel 30 Min After Cangrelor

EXPERIMENTAL

Prasugrel 60 milligram (mg) administered orally 30 min after the discontinuation of cangrelor infusion on Day 1 (2.5 hours \[hrs\] after initiation of cangrelor infusion).

Drug: Cangrelor; Drug: Prasugrel

Clopidogrel Within 5 Min After Cangrelor

EXPERIMENTAL

Clopidogrel 600 mg administered orally within 5 min after the discontinuation of the cangrelor infusion on Day 1 (2 hrs after initiation of cangrelor infusion).

Drug: Cangrelor; Drug: Clopidogrel

Clopidogrel 1.5 Hrs During Cangrelor

EXPERIMENTAL

Clopidogrel 600 mg administered orally 1.5 hrs after the initiation of cangrelor infusion on Day 1.

Drug: Cangrelor; Drug: Clopidogrel

Clopidogrel 1 Hr During Cangrelor

EXPERIMENTAL

Clopidogrel 600 mg administered orally 1 hr after the initiation of cangrelor infusion on Day 1.

Drug: Cangrelor; Drug: Clopidogrel

Interventions

Cangrelor DRUG

Cangrelor intravenously (IV) administered as a 30 microgram (µg)/kilogram (kg) bolus, followed by 4 µg/kg/min infusion for 2 hrs on Day 1.

Clopidogrel 1 Hr During Cangrelor; Clopidogrel 1.5 Hrs During Cangrelor; Clopidogrel Within 5 Min After Cangrelor; Prasugrel 30 Min After Cangrelor

Clopidogrel DRUG

Clopidogrel 600 mg single oral dose

Clopidogrel 1 Hr During Cangrelor; Clopidogrel 1.5 Hrs During Cangrelor; Clopidogrel Within 5 Min After Cangrelor

Prasugrel DRUG

Prasugrel 60 mg single oral dose

Prasugrel 30 Min After Cangrelor

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Greater than or equal to 18 and less than 75 years of age, of either sex, and of any race.
• Stable CAD defined by the following criteria:
• Previous myocardial infarction defined by admission to the hospital with elevation of markers of injury or the presence of pathologic Q-waves on at least 2 contiguous electrocardiogram (ECG) leads.
• Previous revascularization by percutaneous coronary intervention or coronary artery bypass graft, and
• Treatment with aspirin 81 mg daily.

You may not qualify if:

• Known intolerance or contraindication to cangrelor or prasugrel, or any ingredients of the respective formulation.
• Any antiplatelet (other than aspirin) or anticoagulant medication within the previous 30 days.
• Acute coronary syndrome within the previous 12 months.
• History of bleeding diathesis or known coagulopathy such as; impaired hemostasis; known international normalized ratio (INR) \>1.5; past or present bleeding disorder (including congenital bleeding disorders, such as, von Willebrand's disease or hemophilia), acquired bleeding disorders, and unexplained clinically significant bleeding disorders; thrombocytopenia (platelet count less than 100,000/microliter \[µL\]), or history of thrombocytopenia or neutropenia associated with clopidogrel.
• Anemia (for example, hematocrit less than 35%).
• Prior stroke (any type), prior cerebral arteriovenous malformation or intracranial aneurysm; recent (\<1 month) trauma or major surgery (including bypass surgery).
• Known or suspected pregnancy, or lactating females.
• Known severe renal insufficiency (glomerular filtration rate less than 30 milliliter \[mL\]/min).
• Inability to provide informed consent.
• Moderate or severe hepatic impairment as per Investigator's discretion (elevation of liver function tests).
• Inability to swallow oral medication at time of randomization.
• Any clinically significant disease or condition affecting a major organ system, including but not limited to gastrointestinal, renal, hepatic, endocrinologic, broncho-pulmonary, neurological, or metabolic disease.
• Any surgical or medical condition which, in the judgment of the Investigator, might interfere with the pharmacokinetics, distribution, metabolism, or excretion of the study drug (if applicable).
• Treatment with other investigational medicinal products or devices within 30 days or 5 half-lives, whichever is longer, prior to the administration of the drug, or planned use of investigational medicinal products or devices.
• Participants who, for any reason, are deemed by the Investigator to be inappropriate for this study, including participants who are unable to communicate or to cooperate with the Investigator.

Sponsors & Collaborators

• The Medicines Company: lead

Study Sites (1)

Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Related Publications (1)

• Schneider DJ, Agarwal Z, Seecheran N, Gogo P. Pharmacodynamic Effects When Clopidogrel is Given Before Cangrelor Discontinuation. J Interv Cardiol. 2015 Oct;28(5):415-9. doi: 10.1111/joic.12229. Epub 2015 Sep 18.

  PMID: 26381736 RESULT

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

cangrelor; Clopidogrel; Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines

Results Point of Contact

• Title: Global Health Science Center, The Medicines Company
• Organization: The Medicines Company

medical.information@themedco.com

1-888-977-6326

Study Officials

• David J. Schneider, MD

  University of Vermont Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2013
• First Posted: November 8, 2013
• Study Start: December 2, 2013
• Primary Completion: January 20, 2014
• Study Completion: January 20, 2014
• Last Updated: February 26, 2020
• Results First Posted: March 5, 2018

Record last verified: 2020-02

Locations

US (1)