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Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight With Coronary Artery Disease (FEATHER)

Primary Purpose

Coronary Artery Disease

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

prasugrel

clopidogrel

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring Platelet function

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects with a history of stable coronary artery disease who are not currently indicated for treatment with a thienopyridine (that is, prasugrel, clopidogrel, or ticlopidine)
Provision of written informed consent
For women of child-bearing potential only (that is, women who are not surgically or chemically sterilised and who are between menarche and 1 year post menopause), test negative for pregnancy (based on a urine or serum pregnancy test to be performed before randomisation) and agree to use a reliable method of birth control during the study

Exclusion Criteria:

Unstable coronary artery disease
Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft Surgery (CABG) within the previous 90 days
History of refractory ventricular arrhythmias within the last 6 months; an implanted defibrillator device; congestive heart failure within 6 months prior to screening; major surgery, or severe trauma, fracture or organ biopsy within 3 months prior to enrollment
Any planned surgical procedure or any coronary revascularisation (surgical or percutaneous) planned within 60 days following randomisation
Any known contraindication to treatment with an antiplatelet agent
Significant hypertension at the time of screening or randomisation
Clinically significant out-of-range values for platelet count or haemoglobin at screening, in the investigator's opinion, or results of clinical laboratory tests at the time of screening that are judged to be clinically significant for the study population, as determined by the investigator
Prior history or presence of significant bleeding disorders, abnormal bleeding tendency, or personal history of coagulation or bleeding disorders.
Prior history or clinical suspicion of cerebral vascular malformations, intracranial neoplasm, Transient Ischemic Attack (TIA) or stroke.
Prior history of thrombocytopenia or thrombocytosis
Use of antiplatelet agents (besides aspirin) within 10 days prior to screening; the use (or planned use) of heparin, oral anticoagulants, or fibrinolytic agents within 30 days of screening; or subjects receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study

Sites / Locations

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

5 mg prasugrel

10 mg prasugrel

75 mg clopidogrel

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12 (Period 1)

MPA to 20 micromolar (μM) ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA reflects stronger platelet inhibition, whereas a higher MPA reflects weaker inhibition.

Secondary Outcome Measures

Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy

VASP phosphorylation levels, expressed as the platelet reactivity index (PRI), reflect the degree of thienopyridine-mediated P2Y12 receptor inhibition and were used to compare prasugrel versus clopidogrel, in low body weight (LBW) participants compared to higher body weight (HBW) participants. PRI was calculated by VASP. The PRI indicates the level of P2Y12 receptor inhibition. A lower PRI reflects stronger inhibition of P2Y12 receptor thus stronger platelet inhibition, whereas a higher PRI reflects weaker inhibition of P2Y12 receptor and weaker platelet inhibition.

Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy

The Accumetrics VerifyNow® P2Y12 assay measures platelet aggregation in whole blood and is reported in PRU. PRU indicates the extent of P2Y12 receptor-mediated platelet aggregation calculated as a function of rate and extent of platelet aggregation in an adenosine phosphate (ADP)-containing channel of the device. A lower PRU reflects stronger inhibition of platelet aggregation, whereas a higher PRU reflects weaker inhibition of platelet aggregation.

Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC)

A pharmacokinetic-pharmacodynamic (PK-PD) analysis comparing MPA (LTA) and AUC was conducted as originally intended, however the graphic output is not possible here. Therefore, the PK portion is presented here as AUC and the PD portion is presented in Secondary Outcome Measure #5. AUC was calculated through the last scheduled sampling time of 4 hours [AUC (0-4)] or through the sampling time of the last quantifiable concentration prior to 4 hours. AUC values were denoted AUC(0-tlast) in both instances.

Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy

MPA to 20 micromolar (μM) adenosine diphosphate (ADP) was assessed by LTA, an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing platelet-rich plasma stimulated with a platelet activator, such as ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA reflects stronger platelet inhibition, whereas a higher MPA reflects weaker inhibition.

Full Information

NCT ID

NCT01107925

First Posted

April 19, 2010

Last Updated

July 27, 2012

Sponsor

Eli Lilly and Company

Collaborators

Daiichi Sankyo Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT01107925

Brief Title

Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight With Coronary Artery Disease

Acronym

FEATHER

Official Title

A Pharmacokinetic and Pharmacodynamic Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight Aspirin-Treated Subjects With Stable Coronary Artery Disease

Study Type

Interventional

2. Study Status

Record Verification Date

July 2012

Overall Recruitment Status

Completed

Study Start Date

March 2010 (undefined)

Primary Completion Date

August 2011 (Actual)

Study Completion Date

August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

Collaborators

Daiichi Sankyo Co., Ltd.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The 5-milligram (mg) dose of prasugrel in low body weight (LBW) patients with coronary artery disease produces a pharmacodynamic response within the same therapeutic range as 10-mg dose in higher body weight (HBW) patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronary Artery Disease

Keywords

Platelet function

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

72 (Actual)

8. Arms, Groups, and Interventions

Arm Title

5 mg prasugrel

Arm Type

Experimental

Arm Title

10 mg prasugrel

Arm Type

Active Comparator

Arm Title

75 mg clopidogrel

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

prasugrel

Other Intervention Name(s)

Efient, Effient, LY640315, CS747

Intervention Description

Administered orally, daily for 12 days

Intervention Type

Drug

Intervention Name(s)

clopidogrel

Intervention Description

Administered orally, daily for 12 days

Primary Outcome Measure Information:

Title

Change From Baseline in Maximum Platelet Aggregation (MPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at Day 12 (Period 1)

Description

Time Frame

Baseline, Day 12

Secondary Outcome Measure Information:

Title

Change From Baseline in Vasodilator-Associated Stimulated Phosphoprotein (VASP) at Day 12 of Therapy

Description

Time Frame

Baseline, Day 12

Title

Change From Baseline in VerifyNow® P2Y12 Reaction Units (PRU) at Day 12 of Therapy

Description

Time Frame

Baseline, Day 12

Title

Pharmacokinetic (PK) Analysis of the Concentration-Time Curve (AUC)

Description

Time Frame

baseline (pre-dose) up to 4 hours post-dose

Title

Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA) at Day 12 of Therapy

Description

Time Frame

Baseline , Day 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

74 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects with a history of stable coronary artery disease who are not currently indicated for treatment with a thienopyridine (that is, prasugrel, clopidogrel, or ticlopidine) Provision of written informed consent For women of child-bearing potential only (that is, women who are not surgically or chemically sterilised and who are between menarche and 1 year post menopause), test negative for pregnancy (based on a urine or serum pregnancy test to be performed before randomisation) and agree to use a reliable method of birth control during the study Exclusion Criteria: Unstable coronary artery disease Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft Surgery (CABG) within the previous 90 days History of refractory ventricular arrhythmias within the last 6 months; an implanted defibrillator device; congestive heart failure within 6 months prior to screening; major surgery, or severe trauma, fracture or organ biopsy within 3 months prior to enrollment Any planned surgical procedure or any coronary revascularisation (surgical or percutaneous) planned within 60 days following randomisation Any known contraindication to treatment with an antiplatelet agent Significant hypertension at the time of screening or randomisation Clinically significant out-of-range values for platelet count or haemoglobin at screening, in the investigator's opinion, or results of clinical laboratory tests at the time of screening that are judged to be clinically significant for the study population, as determined by the investigator Prior history or presence of significant bleeding disorders, abnormal bleeding tendency, or personal history of coagulation or bleeding disorders. Prior history or clinical suspicion of cerebral vascular malformations, intracranial neoplasm, Transient Ischemic Attack (TIA) or stroke. Prior history of thrombocytopenia or thrombocytosis Use of antiplatelet agents (besides aspirin) within 10 days prior to screening; the use (or planned use) of heparin, oral anticoagulants, or fibrinolytic agents within 30 days of screening; or subjects receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209

Country

United States

Facility Name

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45212

Country

United States

Facility Name

City

Dublin

ZIP/Postal Code

Country

Ireland

Facility Name

City

Nieuwegein

ZIP/Postal Code

3435 CM

Country

Netherlands

Facility Name

City

Lund

ZIP/Postal Code

22185

Country

Sweden

Facility Name

City

Uppsala

ZIP/Postal Code

75185

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

25022828

Citation

Jakubowski JA, Angiolillo DJ, Zhou C, Small DS, Moser BA, Ten Berg JM, Brown PB, James S, Winters KJ, Erlinge D. The influence of body size on the pharmacodynamic and pharmacokinetic response to clopidogrel and prasugrel: a retrospective analysis of the FEATHER study. Thromb Res. 2014 Sep;134(3):552-7. doi: 10.1016/j.thromres.2014.05.019. Epub 2014 May 21.

Results Reference

derived

PubMed Identifier

23083774

Citation

Erlinge D, Ten Berg J, Foley D, Angiolillo DJ, Wagner H, Brown PB, Zhou C, Luo J, Jakubowski JA, Moser B, Small DS, Bergmeijer T, James S, Winters KJ. Reduction in platelet reactivity with prasugrel 5 mg in low-body-weight patients is noninferior to prasugrel 10 mg in higher-body-weight patients: results from the FEATHER trial. J Am Coll Cardiol. 2012 Nov 13;60(20):2032-40. doi: 10.1016/j.jacc.2012.08.964. Epub 2012 Oct 17.

Results Reference

derived

Learn more about this trial

Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight With Coronary Artery Disease

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